NeoplasmPhase 1NCT01920061
A Study Of PF-05212384 In Combination With Other Anti-Tumor Agents and in Combination With Cisplatin in Patients With Triple Negative Breast Cancer in an Expansion Arm (TNBC)
A Phase 1 study testing PF-05212384 (gedatolisib), Docetaxel and Cisplatin in people with Neoplasm, run by Pfizer at 29 sites in 5 countries.
Trial summary
This study will evaluate PF-05212384 (gedatolisib) PI3K/mTOR inhibitor)) in combination with either docetaxel, cisplatin or dacomitinib in select advanced solid tumors. The study will assess the safety, pharmacokinetics and pharmacodynamics of these combinations in patients with advanced cancer in order to determine… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Neoplasm
- What is being tested?
- PF-05212384 (gedatolisib), Docetaxel and Cisplatin
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 110 participants
- Where
- 29 sitesin 5 countries
- Study dates
- 10 Sep 2013to 8 Jan 2020
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Cisplatin Combination Expansion:
- Arm 1:Patients with TNBC with no prior cytotoxic chemotherapy therapy in the metastatic setting; Arm 2: Patients with TNBC and one or two prior cytotoxic therapies in the metastatic setting.
- Arm A: castrate resistant prostate cancer, advanced breast cancer, or non-small cell lunch cancer that are candidates for treatment with a docetaxel-based combination.
- Arm B: Urothelial transitional cell cancer, triple negative breast cancer, ovarian cancer or non small cell lunch cancer that are candidates for a cisplatin-based combination.
- Arm C: Her2+ breast cancer refractory to prior herceptin or lapatinib, her2+ esophagal-gastric cancer, head and neck squamous cell cancer, or non small cell lunch cancer that are candidates for treatment with a dacomitinib-based combination.
- Availability of archival tumor biopsy sample or willing to provide fresh biopsy if not available.
- Eastern Cooperative Oncology Group [ECOG] performance must be 0 or 1.
- Adequate bone marrow, renal and liver function.
Who cannot join
- Prior therapy for Cisplatin Combination Expansion:
- Prior platinum (carboplatin or cisplatin) in either the adjuvant or metastatic setting;
- Prior radiation to >25% bone marrow as estimated by the Investigator.
- Patients with known symptomatic brain metastases.
- Chemotherapy, radiotherapy, biologics or investigational agent within 4 weeks of the lead-in dose.
- Major surgery within 4 weeks of the baseline disease assessments.
Show all 9Show fewer
- >2 prior regimens containing cytotoxic chemotherapy in the metastatic setting.
- Active bacterial, fungal or viral infection.
- Uncontrolled or significant cardiovascular disease.
Trial locations and contacts
29 sites in 5 countries.
29 sites in 5 countries
United States21 sites
University of Colorado Denver CTO (CTRC)
Aurora, Colorado, 80045
University of Colorado Hospital
Aurora, Colorado, 80045
University of Alabama at Birmingham
Birmingham, Alabama, 35233
University of Alabama at Birmingham
Birmingham, Alabama, 35249
Brigham and Women's Hospital
Boston, Massachusetts, 02115
Beth Israel Deaconess Medical Center
Boston, Massachusetts, 02215
Dana Farber Cancer Institute
Boston, Massachusetts, 02215
Medical University of South Carolina/ University Hospital
Charleston, South Carolina, 29425
Medical University of South Carolina
Charleston, South Carolina, 29425
MUSC SCTR Research
Charleston, South Carolina, 29425
Harper Professional Building
Detroit, Michigan, 48201
Karmanos Cancer Institute
Detroit, Michigan, 48201
Ronald Reagan UCLA Medical Center
Los Angeles, California, 90095
UCLA Hematology Oncology
Los Angeles, California, 90095
Westwood Bowyer Clinic
Los Angeles, California, 90095
MUSC Health East Cooper
Mt. Pleasant, South Carolina, 29464
MUSC Specialty Care-North
North Charleston, South Carolina, 29406
Fox Chase Cancer Center
Philadelphia, Pennsylvania, 19111
UCSF Helen Diller Family Comprehensive Cancer Center
San Francisco, California, 94115
Santa Monica UCLA Medical Center & Orthopaedic Hospital
Santa Monica, California, 90404
UCLA Hematology Oncology
Santa Monica, California, 90404
Canada2 sites
Princess Margaret Cancer Center
Toronto, Ontario, M5G 2M9
British Columbia Cancer Agency - Vancouver Centre
Vancouver, British Columbia, V5Z 4E6
Italy2 sites
Istituto Europeo di Oncologia - Divisione Sviluppo di Nuovi Farmaci per Terapie Innovative
Milan, MI, 20141
Istituto Regina Elena Struttura Complessa Oncologia Medica A
Roma, RM, 00144
Spain2 sites
Hospital Universitari Vall d'Hebron
Barcelona, 08035
Hospital Universitario 12 de Octubre
Madrid, 28041
United Kingdom2 sites
University College London Hospital, NIHR UCLH Clinical Research Facility
London, W1T 7HA
Oxford Cancer Centre
Oxford, OX3 7LE
About this study
Official title: A PHASE 1B OPEN-LABEL THREE-ARM MULTI-CENTER STUDY TO ASSESS THE SAFETY AND TOLERABILITY OF PF-05212384 (PI3K/MTOR INHIBITOR) IN COMBINATION WITH OTHER ANTI-TUMOR AGENTS
This study will evaluate PF-05212384 (gedatolisib) PI3K/mTOR inhibitor)) in combination with either docetaxel, cisplatin or dacomitinib in select advanced solid tumors. The study will assess the safety, pharmacokinetics and pharmacodynamics of these combinations in patients with advanced cancer in order to determine the maximum tolerated dose in each combination. The cisplatin combination expansion portion will evaluate the anti tumor activity of PF 05212384 plus cisplatin in patients with TNBC in 2 separate Arms (Arm 1 and Arm 2).
- Conditions
- Neoplasm
- Keywords
- Advanced cancer, solid tumors, PI3K, mTOR, PI3K/mTOR, metastatic, Triple Negative Breast Cancer (TNBC)
- Medical subject headings
- Neoplasms, Neoplasm Metastasis, Triple Negative Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PF-05212384 (gedatolisib)Drug
PF-05212384 weekly intravenous infusions starting at 90 mg/wk as a 3 week cycle
DocetaxelDrug
Docetaxel intravenous infusions once every 3 weeks starting at 75 mg/m^2
CisplatinDrug
Cisplatin intravenous infusions once every 3 weeks starting at 75 mg/m^2
DacomitinibDrug
Dacomitinib to be taken orally as a continuous once daily regimen at a starting dose of 30 mg
| Study group | Role | What they receive |
|---|---|---|
| Arm A | Experimental | Not described Receives: Drug: PF-05212384 (gedatolisib); Drug: Docetaxel |
| Arm B | Experimental | Not described Receives: Drug: PF-05212384 (gedatolisib); Drug: Cisplatin |
| Arm C | Experimental | Not described Receives: Drug: PF-05212384 (gedatolisib); Drug: Dacomitinib |
| Expansion Arm 1 | Experimental | Not described Receives: Drug: PF-05212384 (gedatolisib); Drug: Cisplatin |
| Expansion Arm 2 | Experimental | Not described Receives: Drug: PF-05212384 (gedatolisib); Drug: Cisplatin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Dose Limiting Toxicities (DLTs) - Arms A, B and C
DLT was defined as any of the following adverse events (AEs) attributable to the combination: (1) hematologic: grade 4 neutropenia lasting >7 days; febrile neutropenia; grade >=3 neutropenia with infection; grade 3 thrombocytopenia with bleeding; grade 4 thrombocytopenia; (2) non-hematologic: grade >=2 pneumonitis; grade>=3 toxicities, except pneumonitis, and excluding those that had not been maximally treated; persistent, intolerable toxicities which resulted in the failure to deliver at least 3 of the 4 doses of PF-05212384 for Arms A and B or at least 3 of the 4 doses of PF-05212384 and 75% of dacomitinib for Arm C during the first cycle; the persistent, intolerable toxicities which result in delay of the start of the second cycle by more than 2 weeks relative to the scheduled start; in an asymptomatic participant, the grade 3 QTc prolongation persists after correction of any reversible causes.
Measured: Up to 21 days
Percentage of Participants With Objective Response - Arm B Expansion
Percentage of participants with objective response based on the assessment of confirmed complete response (CR) or confirmed partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST v1.1). Confirmed responses are those that persist on repeat imaging study at least 4 weeks after initial documentation of response.
Per RECIST v1.1: CR was defined as complete disappearance of all target lesions and non-target disease, with the exception of nodal disease. All nodes, both target and non-target, must decrease to normal (short axis <10 mm) and no new lesions. PR was defined as >=30% decrease under baseline of the sum of diameters of all target lesions. The short axis was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. No unequivocal progression of non-target disease and no new lesions.
Measured: Cycle 1 Day 1 up to 18 months
Secondary outcomes (67)
Number of Participants With Treatment-Emergent Adverse Events (All Causality) - Arms A, B, C and B Expansion
An adverse event (AE) was any untoward medical occurrence in a clinical investigation participants administered a product or medical device; the event needed not necessarily have a causal relationship with the treatment or usage. Treatment Emergent AEs were those occurred for the first time after the start of study treatment and within 28 days after final dose of study treatment and was not seen prior to the start of treatment, or those were seen prior to the start of study treatment but increased in Common Terminology Criteria for Adverse Events (CTCAE) grade after the start of study treatment and within 28 days after final dose of study treatment. AEs were graded by the investigator according to the CTCAE version 4.03 : Grade 1: mild AE; Grade 2: moderate AE; Grade 3: severe AE; Grade 4: life-threatening consequences, urgent intervention indicated; Grade 5: death related to AE.
Measured: From the first dose of study drugs up to 28 days after the last dose of study drugs. Maximum duration between first and last dose: 505 days for Arm A, 414 days for Arm B, 842 days for Arm C, 728 days for Arm B Expansion.
Number of Participants With Treatment-Emergent Adverse Events (Treatment Related) - Arms A, B, C and B Expansion
An adverse event (AE) was any untoward medical occurrence in a clinical investigation participants administered a product or medical device; the event needed not necessarily have a causal relationship with the treatment or usage. Treatment Emergent AEs were those occurred for the first time after the start of study treatment and within 28 days after final dose of study treatment and was not seen prior to the start of treatment, or those were seen prior to the start of study treatment but increased in Common Terminology Criteria for Adverse Events (CTCAE) grade after the start of study treatment and within 28 days after final dose of study treatment. AEs were graded by the investigator according to the CTCAE version 4.03 : Grade 1: mild AE; Grade 2: moderate AE; Grade 3: severe AE; Grade 4: life-threatening consequences, urgent intervention indicated; Grade 5: death related to AE.
Measured: From the first dose of study drugs up to 28 days after the last dose of study drugs. Maximum duration between first and last dose: 505 days for Arm A, 414 days for Arm B, 842 days for Arm C, 728 days for Arm B Expansion.
Number of Participants With Laboratory Abnormalities by Severity (All Cycles) - Hematology
Laboratory abnormalities were graded per National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 (Grade 0: no change from normal or reference range; Grade 1: mild AE; Grade 2: moderate AE; Grade 3: severe AE; Grade 4: life-threatening consequences, urgent intervention indicated) and those with at least 1 participant are presented here. Following parameters were analyzed for laboratory examination: anemia,hemoglobin increased, platelets, white blood cells, absolute neutrophils,lymphocyte count increased, lymphopenia.
Measured: From the first dose of study drugs up to 28 days after the last dose of study drugs. Maximum duration between first and last dose: 505 days for Arm A, 414 days for Arm B, 842 days for Arm C, 728 days for Arm B Expansion.
Number of Participants With Laboratory Abnormalities by Severity (All Cycles) - Coagulation
Laboratory abnormalities were graded per NCI CTCAE version 4.03 (Grade 0: no change from normal or reference range; Grade 1: mild AE; Grade 2: moderate AE; Grade 3: severe AE; Grade 4: life-threatening consequences, urgent intervention indicated) and those with at least 1 participant are presented here. Following parameters were analyzed for laboratory examination: partial thromboplastin time and prothrombin time international normalized ratio(INR).
Measured: From the first dose of study drugs up to 28 days after the last dose of study drugs. Maximum duration between first and last dose: 505 days for Arm A, 414 days for Arm B, 842 days for Arm C, 728 days for Arm B Expansion.
Number of Participants With Laboratory Abnormalities by Severity (All Cycles) - Chemistry
Laboratory abnormalities were graded per NCI CTCAE version 4.03 (Grade 0: no change from normal or reference range; Grade 1: mild AE; Grade 2: moderate AE; Grade 3: severe AE; Grade 4: life-threatening consequences, urgent intervention indicated) and those with at least 1 participant are presented here. Following parameters were analyzed for laboratory examination: alanine aminotransferase (ALT), alkaline phosphatase, aspartate aminotransferase (AST), total bilirubin, creatinine, hypercalcemia, hyperglycemia, hyperkalemia, hypermagnesemia, hypernatremia, hypoalbuminemia, hypocalcemia, hypoglycemia, hypokalemia, hypomagnesemia, hyponatremia, and hypophosphatemia.
Measured: From the first dose of study drugs up to 28 days after the last dose of study drugs. Maximum duration between first and last dose: 505 days for Arm A, 414 days for Arm B, 842 days for Arm C, 728 days for Arm B Expansion.
Number of Participants With Laboratory Abnormalities by Severity (All Cycles) - Urinalysis
Laboratory abnormalities were graded per NCI CTCAE version 4.03 (Grade 0: no change from normal or reference range; Grade 1: mild AE; Grade 2: moderate AE; Grade 3: severe AE; Grade 4: life-threatening consequences, urgent intervention indicated) and those with at least 1 participant are presented here. Following parameter was analyzed for laboratory examination: urine protein.
Measured: From the first dose of study drugs up to 28 days after the last dose of study drugs. Maximum duration between first and last dose: 505 days for Arm A, 414 days for Arm B, 842 days for Arm C, 728 days for Arm B Expansion.
Number of Participants With Vital Signs Data Meeting Pre-defined Criteria
Blood pressure (BP), including systolic BP (SBP) and diastolic BP (DBP), and pulse rate were recorded in sitting position.
Measured: From baseline up to follow up (at least 28 days and no more than 35 days after discontinuation of treatment). Maximum duration between first and last dose: 842 days.
Maximum Observed Plasma Concentration (Cmax) Following Single IV Infusion Dose of PF-05212384 Alone - Plasma PF-05212384 (Arms A, B and C)
Cmax is defined as maximum observed plasma concentration.
Measured: Pre-dose, 0.5, 1, 2, 4, 6, 24, 72, 96 and 168 hours post-dose 7 days prior to Cycle 1 Day 1 for Arms A and B; pre-dose, 0.5, 1, 2, 4, 6, 24, 72, 96 and 168 hours post-dose 14 days prior to Cycle 1 Day 1 for Arm C.
Maximum Observed Plasma Concentration (Cmax) Following Single IV Infusion Dose of PF-05212384 in Combination With Cisplatin - Plasma PF-05212384 (Arm B Expansion)
Cmax is defined as maximum observed plasma concentration.
Measured: Pre-dose, 0.5, 1, 2, 4, 6, 24, 72, 96 and 168 (predose Day 8) hours post-dose on Cycle 1 Day 1.
Maximum Observed Plasma Concentration (Cmax) Following Multiple IV Infusion Doses of PF-05212384 in Combination With Docetaxel- Plasma PF-05212384 (Arm A)
Cmax is defined as maximum observed plasma concentration.
Measured: Pre-dose, 0.5, 1, 2, 4, 6, 24, 72, 96 and 168 hours post-dose on Cycle 2 Day 1.
Maximum Observed Plasma Concentration (Cmax) Following Multiple IV Infusion Doses of PF-05212384 in Combination With Cisplatin - Plasma PF-05212384 (Arm B)
Cmax is defined as maximum observed plasma concentration.
Measured: Pre-dose, 0.5, 1, 2, 4, 6, 24, 72, 96 and 168 hours post-dose on Cycle 2 Day 1.
Maximum Observed Plasma Concentration (Cmax) Following Multiple IV Infusion Doses of PF-05212384 in Combination With Dacomitinib - Plasma PF-05212384 (Arm C)
Cmax is defined as maximum observed plasma concentration.
Measured: Pre-dose, 0.5, 1, 2, 4, 6, 24, 72, 96 and 168 hours post-dose on Cycle 2 Day 1.
Maximum Observed Plasma Concentration (Cmax) Following Multiple IV Infusion Doses of PF-05212384 in Combination With Cisplatin - Plasma PF-05212384 (Arm B Expansion)
Cmax is defined as maximum observed plasma concentration.
Measured: Pre-dose, 0.5, 1, 2, 4, 6, 24, 72, 96 and 168 (predose Day 8) hours post-dose on Cycle 2 Day 1.
Maximum Observed Plasma Concentration (Cmax) Following Single IV Infusion Dose of Docetaxel Alone- Plasma Docetaxel (Arm A)
Cmax is defined as maximum observed plasma concentration.
Measured: Pre-dose, 1, 1.5, 2, 4, 6, and 24 hours post-dose on Cycle 1 Day 1.
Maximum Observed Plasma Concentration (Cmax) Following Administration of Docetaxel IV Infusion in Combination With PF-05212384 - Plasma Docetaxel (Arm A)
Cmax is defined as maximum observed plasma concentration.
Measured: Pre-dose, 1, 1.5, 2, 4, 6, and 24 hours post-dose on Cycle 2 Day 1.
Maximum Observed Plasma Concentration (Cmax) Following Single IV Infusion Dose of Cisplatin Alone - Plasma Platinum (Arm B)
Cmax is defined as maximum observed plasma concentration.
Measured: Pre-dose, 2, 2.5, 3, 4, 6, and 24 hours post-dose on Cycle 1 Day 1.
Maximum Observed Plasma Concentration (Cmax) Following Administration of Cisplatin IV Infusion in Combination With PF-05212384 - Plasma Platinum (Arm B)
Cmax is defined as maximum observed plasma concentration.
Measured: Pre-dose, 2, 2.5, 3, 4, 6, and 24 hours post-dose on Cycle 2 Day 1.
Maximum Observed Plasma Concentration (Cmax) Following Multiple Oral Doses of Dacomitinib Alone - Plasma Dacomitinib (Arm C)
Cmax is defined as maximum observed plasma concentration.
Measured: Pre-dose, 1, 2, 4, 6, and 24 hours post-dose on Cycle 1 Day 1.
Maximum Observed Plasma Concentration (Cmax) Following Multiple Oral Doses of Dacomitinib in Combination With PF-05212384 - Plasma Dacomitinib (Arm C)
Cmax is defined as maximum observed plasma concentration.
Measured: Pre-dose, 1, 2, 4, 6, and 24 hours post-dose on Cycle 2 Day 1.
Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) Following Single IV Infusion Dose of PF-05212384 Alone - Plasma PF-05212384 (Arms A, B and C)
AUClast is defined as area under the curve from time zero to last quantifiable concentration.
Measured: Pre-dose, 0.5, 1, 2, 4, 6, 24, 72, 96 and 168 hours post-dose 7 days prior to Cycle 1 Day 1 for Arms A and B; pre-dose, 0.5, 1, 2, 4, 6, 24, 72, 96 and 168 hours post-dose 14 days prior to Cycle 1 Day 1 for Arm C.
Area Under the Concentration-time Profile From Time 0 to Time Tau (AUCtau) Following Multiple IV Infusion Doses of PF-05212384 in Combination With Docetaxel- Plasma PF-05212384 (Arm A)
AUCtau is defined as area under the concentration-time profile from time 0 to time tau.
Measured: Pre-dose, 0.5, 1, 2, 4, 6, 24, 72, 96 and 168 hours post-dose on Cycle 2 Day 1.
Area Under the Concentration-time Profile From Time 0 to Time Tau (AUCtau) Following Multiple IV Infusion Doses of PF-05212384 in Combination With Cisplatin - Plasma PF-05212384 (Arm B)
AUCtau is defined as area under the concentration-time profile from time 0 to time tau.
Measured: Pre-dose, 0.5, 1, 2, 4, 6, 24, 72, 96 and 168 hours post-dose 7 days prior to Cycle 2 Day 1.
Area Under the Concentration-time Profile From Time 0 to Time Tau (AUCtau) Following Multiple IV Infusion Doses of PF-05212384 in Combination With Dacomitinib - Plasma PF-05212384 (Arm C)
AUCtau is defined as area under the concentration-time profile from time 0 to time tau.
Measured: Pre-dose, 0.5, 1, 2, 4, 6, 24, 72, 96 and 168 hours post-dose on Cycle 2 Day 1.
Area Under the Concentration-time Profile From Time 0 to Time Tau (AUCtau) Following Single IV Infusion Dose of PF-05212384 in Combination With Cisplatin - Plasma PF-05212384 (Arm B Expansion)
AUCtau is defined as area under the concentration-time profile from time 0 to time tau.
Measured: Pre-dose, 0.5, 1, 2, 4, 6, 24, 72, 96 and 168 (predose Day 8) hours post-dose on Cycle 1 Day 1.
Area Under the Concentration-time Profile From Time 0 to Time Tau (AUCtau) Following Multiple IV Infusion Doses of PF-05212384 in Combination With Cisplatin - Plasma PF-05212384 (Arm B Expansion)
AUCtau is defined as area under the concentration-time profile from time 0 to time tau.
Measured: Pre-dose, 0.5, 1, 2, 4, 6, 24, 72, 96 and 168 (predose Day 8) hours post-dose on Cycle 2 Day 1.
Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) Following Single IV Infusion Dose of Docetaxel Alone- Plasma Docetaxel (Arm A)
AUClast is defined as area under the curve from time zero to last quantifiable concentration.
Measured: Pre-dose, 1, 1.5, 2, 4, 6, and 24 hours post-dose on Cycle 1 Day 1.
Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) Following Administration of Docetaxel in Combination With PF-05212384 - Plasma Docetaxel (Arm A)
AUClast is defined as area under the curve from time zero to last quantifiable concentration.
Measured: Pre-dose, 1, 1.5, 2, 4, 6, and 24 hours post-dose on Cycle 2 Day 1.
Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) Following Single IV Infusion Dose of Cisplatin Alone - Plasma Platinum (Arm B)
AUClast is defined as area under the curve from time zero to last quantifiable concentration.
Measured: Pre-dose, 2, 2.5, 3, 4, 6, and 24 hours post-dose on Cycle 1 Day 1.
Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) Following Administration of Cisplatin IV Infusion in Combination With PF-05212384 - Plasma Platinum (Arm B)
AUClast is defined as area under the curve from time zero to last quantifiable concentration.
Measured: Pre-dose, 2, 2.5, 3, 4, 6, and 24 hours post-dose on Cycle 2 Day 1.
Area Under the Concentration-time Profile From Time 0 to Time Tau (AUCtau) Following Multiple Oral Doses of Dacomitinib Alone - Plasma Dacomitinib (Arm C)
AUCtau is defined as area under the concentration-time profile from time 0 to time tau.
Measured: Pre-dose, 1, 2, 4, 6, and 24 hours post-dose on Cycle 1 Day 1.
Area Under the Concentration-time Profile From Time 0 to Time Tau (AUCtau) Following Multiple Oral Doses of Dacomitinib in Combination With PF-05212384 - Plasma Dacomitinib (Arm C)
AUCtau is defined as area under the concentration-time profile from time 0 to time tau.
Measured: Pre-dose, 1, 2, 4, 6, and 24 hours post-dose on Cycle 2 Day 1.
Time to Reach Maximum Observed Plasma Concentration (Tmax) Following Single IV Infusion Dose of PF-05212384 Alone - Plasma PF-05212384 (Arms A, B and C)
Tmax is defined as time to reach maximum observed plasma concentration.
Measured: Pre-dose, 0.5, 1, 2, 4, 6, 24, 72, 96 and 168 hours post-dose 7 days prior to Cycle 1 Day 1 for Arms A and B; pre-dose, 0.5, 1, 2, 4, 6, 24, 72, 96 and 168 hours post-dose 14 days prior to Cycle 1 Day 1 for Arm C.
Time to Reach Maximum Observed Plasma Concentration (Tmax) Following Multiple IV Infusion Doses of PF-05212384 in Combination With Docetaxel- Plasma PF-05212384 (Arm A)
Tmax is defined as time to reach maximum observed plasma concentration.
Measured: Pre-dose, 0.5, 1, 2, 4, 6, 24, 72, 96 and 168 hours post-dose on Cycle 2 Day 1.
Time to Reach Maximum Observed Plasma Concentration (Tmax) Following Multiple IV Infusion Doses of PF-05212384 in Combination With Cisplatin - Plasma PF-05212384 (Arm B)
Tmax is defined as time to reach maximum observed plasma concentration.
Measured: Pre-dose, 0.5, 1, 2, 4, 6, 24, 72, 96 and 168 hours post-dose on Cycle 2 Day 1.
Time to Reach Maximum Observed Plasma Concentration (Tmax) Following Multiple IV Infusion Doses of PF-05212384 in Combination With Dacomitinib - Plasma PF-05212384 (Arm C)
Tmax is defined as time to reach maximum observed plasma concentration.
Measured: Pre-dose, 0.5, 1, 2, 4, 6, 24, 72, 96 and 168 hours post-dose on Cycle 2 Day 1.
Time to Reach Maximum Observed Plasma Concentration (Tmax) Following Single IV Infusion Dose of Docetaxel Alone- Plasma Docetaxel (Arm A)
Tmax is defined as time to reach maximum observed plasma concentration.
Measured: Pre-dose, 1, 1.5, 2, 4, 6, and 24 hours post-dose on Cycle 1 Day 1.
Time to Reach Maximum Observed Plasma Concentration (Tmax) Following Administration of Docetaxel IV Infusion in Combination With PF-05212384 - Plasma Docetaxel (Arm A)
Tmax is defined as time to reach maximum observed plasma concentration.
Measured: Pre-dose, 1, 1.5, 2, 4, 6, and 24 hours post-dose on Cycle 2 Day 1.
Time to Reach Maximum Observed Plasma Concentration (Tmax) Following Single IV Infusion Dose of Cisplatin Alone - Plasma Platinum (Arm B)
Tmax is defined as time to reach maximum observed plasma concentration.
Measured: Pre-dose, 2, 2.5, 3, 4, 6, and 24 hours post-dose on Cycle 1 Day 1.
Time to Reach Maximum Observed Plasma Concentration (Tmax) Following Administration of Cisplatin IV Infusion in Combination With PF-05212384 - Plasma Platinum (Arm B)
Tmax is defined as time to reach maximum observed plasma concentration.
Measured: Pre-dose, 2, 2.5, 3, 4, 6, and 24 hours post-dose on Cycle 2 Day 1.
Time to Reach Maximum Observed Plasma Concentration (Tmax) Following Multiple Oral Doses of Dacomitinib Alone - Plasma Dacomitinib (Arm C)
Tmax is defined as time to reach maximum observed plasma concentration.
Measured: Pre-dose, 1, 2, 4, 6, and 24 hours post-dose on Cycle 1 Day 1.
Time to Reach Maximum Observed Plasma Concentration (Tmax) Following Multiple Oral Doses of Dacomitinib in Combination With PF-05212384 - Plasma Dacomitinib (Arm C)
Tmax is defined as time to reach maximum observed plasma concentration.
Measured: Pre-dose, 1, 2, 4, 6, and 24 hours post-dose on Cycle 2 Day 1.
Time to Reach Maximum Observed Plasma Concentration (Tmax) Following Single IV Infusion Dose of PF-05212384 in Combination With Cisplatin - Plasma PF-05212384 (Arm B Expansion)
Tmax is defined as time to reach maximum observed plasma concentration.
Measured: Pre-dose, 0.5, 1, 2, 4, 6, 24, 72, 96 and 168 (predose Day 8) hours post-dose on Cycle 1 Day 1.
Time to Reach Maximum Observed Plasma Concentration (Tmax) Following Multiple IV Infusion Doses of PF-05212384 in Combination With Cisplatin - Plasma PF-05212384 (Arm B Expansion)
Tmax is defined as time to reach maximum observed plasma concentration.
Measured: Pre-dose, 0.5, 1, 2, 4, 6, 24, 72, 96 and 168 (predose Day 8) hours post-dose on Cycle 2 Day 1.
Mean Serum Biomarkers for Glucose - Baseline
A phosphatidylinositol 3 kinase/mammalian target of rapamycin (PI3K/mTOR) inhibitor should disrupt the cellular uptake and metabolism of glucose. This study employed metabolic biomarkers such as glucose as pharmacodynamics markers for dual PI3K/mTOR inhibition.
Measured: Baseline
Mean Serum Biomarkers for Glucose - End of Treatment
A phosphatidylinositol 3 kinase/mammalian target of rapamycin (PI3K/mTOR) inhibitor should disrupt the cellular uptake and metabolism of glucose. This studies employed metabolic biomarkers such as glucose as pharmacodynamics markers for dual PI3K/mTOR inhibition.
Measured: End of treatment. Maximum duration between first and last dose: 505 days for Arm A, 414 days for Arm B, 842 days for Arm C, 728 days for Arm B Expansion.
Mean Serum Biomarkers for Insulin - Baseline
A phosphatidylinositol 3 kinase/mammalian target of rapamycin (PI3K/mTOR) inhibitor should disrupt the cellular uptake and metabolism of glucose. This studies employed metabolic biomarkers such as insulin as pharmacodynamics markers for dual PI3K/mTOR inhibition.
Measured: Baseline
Mean Serum Biomarkers for Insulin - End of Treatment
A phosphatidylinositol 3 kinase/mammalian target of rapamycin (PI3K/mTOR) inhibitor should disrupt the cellular uptake and metabolism of glucose. This studies employed metabolic biomarkers such as insulin as pharmacodynamics markers for dual PI3K/mTOR inhibition.
Measured: End of treatment. Maximum duration between first and last dose: 505 days for Arm A, 414 days for Arm B, 842 days for Arm C, 728 days for Arm B Expansion.
Mean Serum Biomarkers for Hemoglobin A1c (HbA1c) - Baseline
A phosphatidylinositol 3 kinase/mammalian target of rapamycin (PI3K/mTOR) inhibitor should disrupt the cellular uptake and metabolism of glucose. This studies employed metabolic biomarkers such as hemoglobin A1c (HbA1c) as pharmacodynamics markers for dual PI3K/mTOR inhibition.
Measured: Baseline
Mean Serum Biomarkers for Hemoglobin A1c (HbA1c) - End of Treatment
A phosphatidylinositol 3 kinase/mammalian target of rapamycin (PI3K/mTOR) inhibitor should disrupt the cellular uptake and metabolism of glucose. This studies employed metabolic biomarkers such as hemoglobin A1c (HbA1c) as pharmacodynamics markers for dual PI3K/mTOR inhibition.
Measured: End of treatment. Maximum duration between first and last dose: 505 days for Arm A, 414 days for Arm B, 842 days for Arm C, 728 days for Arm B Expansion.
Percentage of Participants With BRAF and KRAS Mutations in Population of Breast Cancer - Arms A and C
Biopsies were obtained at screening and after drug administration. These samples were analyzed predominantly for phosphoprotein biomarkers indicative of pathway modulation, or for genetic markers correlated to drug sensitivity (eg, emerging KRAS mutation and BRAF mutation). BRAF mutation categories included BRAF mutation status and V600E. KRAS mutation categories included GLY12ALA, GLY12ARG, GLY12ASP, GLY12CYS, GLY12SER, GLY12VAL and GLY13ASP.
Measured: Baseline
Percentage of Participants With BRAF and KRAS Mutations in Population of Non-Small Cell Lung Cancer - Arms A, B and C
Biopsies were obtained at screening and after drug administration. These samples were analyzed predominantly for phosphoprotein biomarkers indicative of pathway modulation, or for genetic markers correlated to drug sensitivity (eg, emerging KRAS mutation and BRAF mutation). BRAF mutation categories included BRAF mutation status and V600E. KRAS mutation categories included GLY12ALA, GLY12ARG, GLY12ASP, GLY12CYS, GLY12SER, GLY12VAL and GLY13ASP.
Measured: Baseline
Percentage of Participants With BRAF and KRAS Mutations in Population of Prostate Cancer - Arm A
Biopsies were obtained at screening and after drug administration. These samples were analyzed predominantly for phosphoprotein biomarkers indicative of pathway modulation, or for genetic markers correlated to drug sensitivity (eg, emerging KRAS mutation and BRAF mutation). BRAF mutation categories included BRAF mutation status and V600E. KRAS mutation categories included GLY12ALA, GLY12ARG, GLY12ASP, GLY12CYS, GLY12SER, GLY12VAL and GLY13ASP.
Measured: Baseline
Percentage of Participants With BRAF and KRAS Mutations in Population of Ovarian Cancer - Arm B
Biopsies were obtained at screening and after drug administration. These samples were analyzed predominantly for phosphoprotein biomarkers indicative of pathway modulation, or for genetic markers correlated to drug sensitivity (eg, emerging KRAS mutation and BRAF mutation). BRAF mutation category was BRAF mutation status. KRAS mutation categories included GLY12ALA, GLY12ARG, GLY12ASP, GLY12CYS, GLY12SER, GLY12VAL and GLY13ASP.
Measured: Baseline
Percentage of Participants With BRAF and KRAS Mutations in Population of Transitional Cell Carcinoma - Arm B
Biopsies were obtained at screening and after drug administration. These samples were analyzed predominantly for phosphoprotein biomarkers indicative of pathway modulation, or for genetic markers correlated to drug sensitivity (eg, emerging KRAS mutation and BRAF mutation). BRAF mutation categories included BRAF mutation status and V600E. KRAS mutation categories included GLY12ALA, GLY12ARG, GLY12ASP, GLY12CYS, GLY12SER, GLY12VAL and GLY13ASP.
Measured: Baseline
Percentage of Participants With BRAF and KRAS Mutations in Population of Triple Negative Breast Cancer - Arm B
Biopsies were obtained at screening and after drug administration. These samples were analyzed predominantly for phosphoprotein biomarkers indicative of pathway modulation, or for genetic markers correlated to drug sensitivity (eg, emerging KRAS mutation and BRAF mutation). BRAF mutation categories included BRAF mutation status and V600E. KRAS mutation categories included GLY12ALA, GLY12ARG, GLY12ASP, GLY12CYS, GLY12SER, GLY12VAL and GLY13ASP.
Measured: Baseline
Percentage of Participants With BRAF and KRAS Mutations in Population of Head and Neck Cancer - Arm C
Biopsies were obtained at screening and after drug administration. These samples were analyzed predominantly for phosphoprotein biomarkers indicative of pathway modulation, or for genetic markers correlated to drug sensitivity (eg, emerging KRAS mutation and BRAF mutation). BRAF mutation categories included BRAF mutation status and V600E. KRAS mutation categories included GLY12ALA, GLY12ARG, GLY12ASP, GLY12CYS, GLY12SER, GLY12VAL and GLY13ASP.
Measured: Baseline
Percentage of Participants With BRAF and KRAS Mutations in Population of Oesophageal Carcinoma - Arm C
Biopsies were obtained at screening and after drug administration. These samples were analyzed predominantly for phosphoprotein biomarkers indicative of pathway modulation, or for genetic markers correlated to drug sensitivity (eg, emerging KRAS mutation and BRAF mutation). BRAF mutation categories included BRAF mutation status and V600E. KRAS mutation categories included GLY12ALA, GLY12ARG, GLY12ASP, GLY12CYS, GLY12SER, GLY12VAL and GLY13ASP.
Measured: Baseline
Number of Participants With Maximum Increase From Baseline in Corrected QT (QTc) Interval
Triplicate 12-lead ECG measurements (each recording separated by approximately 2 minutes) were performed and average was calculated. The time corresponding to beginning of depolarization to repolarization of the ventricles (QT interval) was adjusted for RR interval using QT and RR from each ECG by Fridericia's formula (QTcF = QT divided by cube root of RR) and by Bazette's formula (QTcB = QT divided by square root of RR). Participants with maximum increase from baseline of 30 to less than (<) 60 msec(borderline) and greater than or equal to (>=) 60 msec (prolonged) were summarized.
Measured: Baseline, Cycle 1 Day 1 (for Arm B Expansion), Cycle 1 Day 2 (for Arms A, B and C), Cycle 2 Day 1 (for Arms A, B and C), Day 1 for each cycle (Cycles 3-36, for Arms B Expansion and C) and end of treatment (up to 2 years, for Arms B Expansion and C).
Number of Participants With Maximum Corrected QT (QTc) Interval Meeting Pre-defined Criteria
QT interval corrected using Fridericia's formula (QTcF) and Bazette's formula (QTcB): QT interval (time corresponding to the beginning of depolarization to re-polarization of the ventricles) divided by cube root of RR interval. Maximum QTcF was categorized as less than (<) 450 milliseconds (msec), 450 msec to 480 msec, 480 msec to 500 msec, and more than (>) 500 msec.
Measured: Baseline, Cycle 1 Day 1 (for Arm B Expansion), Cycle 1 Day 2 (for Arms A, B and C), Cycle 2 Day 1 (for Arms A, B and C), Day 1 for each cycle (Cycles 3-36, for Arms B Expansion and C) and end of treatment (up to 2 years, for Arms B Expansion and C).
Percentage of Participants With Objective Response - Arm A
Percentage of participants with objective response based on the assessment of complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST v1.1). Per RECIST v1.1: CR was defined as complete disappearance of all target lesions and non-target disease, with the exception of nodal disease. All nodes, both target and non-target, must decrease to normal (short axis <10 mm) and no new lesions. PR was defined as >=30% decrease under baseline of the sum of diameters of all target lesions. The short axis was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. No unequivocal progression of non-target disease and no new lesions.
Measured: Baseline up to 18 months.
Percentage of Participants With Objective Response - Arm B
Percentage of participants with objective response based on the assessment of complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST v1.1). Per RECIST v1.1: CR was defined as complete disappearance of all target lesions and non-target disease, with the exception of nodal disease. All nodes, both target and non-target, must decrease to normal (short axis <10 mm) and no new lesions. PR was defined as >=30% decrease under baseline of the sum of diameters of all target lesions. The short axis was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. No unequivocal progression of non-target disease and no new lesions.
Measured: Baseline up to 18 months.
Percentage of Participants With Objective Response - Arm C
Percentage of participants with objective response based on the assessment of complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST v1.1). Per RECIST v1.1: CR was defined as complete disappearance of all target lesions and non-target disease, with the exception of nodal disease. All nodes, both target and non-target, must decrease to normal (short axis <10 mm) and no new lesions. PR was defined as >=30% decrease under baseline of the sum of diameters of all target lesions. The short axis was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. No unequivocal progression of non-target disease and no new lesions.
Measured: Baseline up to 18 months.
Clinical Benefit Response Rate - Arm B Expansion
Percent of participants with confirmed complete response (CR), partial response (PR) or stable disease (SD) for at least 24 weeks on study according to Response Evaluation Criteria in Solid Tumors (RECIST). Per RECIST v1.1: CR was defined as complete disappearance of all target lesions and non-target disease, with the exception of nodal disease. All nodes, both target and non-target, must decrease to normal (short axis <10 mm) and no new lesions. PR was defined as >=30% decrease under baseline of the sum of diameters of all target lesions. The short axis was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. No unequivocal progression of non-target disease and no new lesions. SD was defined as not qualifying for CR, PR, Progressive Disease (PD).
Measured: Baseline up to 18 months.
Duration of Response - Arm B Expansion
Duration of response was calculated from first date of partial response (PR) or complete response (CR) to the date of progression or death due to any cause. In the event of no progression or death, the last tumor assessment date without progression was used in this calculation.
Measured: Baseline up to 18 months.
Progression Free Survival - Arm B Expansion
Progression free survival (PFS) defined as the time from first dose of study treatment to date of first documentation of progression or death due to any cause, whichever occurs first. PFS was calculated as first event date minus the date of first dose of study medication plus 1 . Tumor progression was determined from oncologic assessment data (where data meet the criteria for progressive disease [PD]), or from adverse event (AE) data (where the outcome was "Death").
Measured: Baseline up to 18 months.
Mean Observed Score Values for European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (EORTC QLQ-C30) - Arm B Expansion
European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (EORTC QLQ-C30): included functional scales (physical, role, cognitive, emotional, and social), global health status, symptom scales (fatigue, pain, nausea/vomiting) and single items (dyspnoea, appetite loss, insomnia, constipation/diarrhea and financial difficulties). Most questions used 4 point scale (1 'Not at all' to 4 'Very much'; 2 questions used 7-point scale (1 'very poor' to 7 'Excellent'). Scores averaged, transformed to 0-100 scale; higher score=better level of functioning or greater degree of symptoms.
Measured: Baseline, Day 1 and Day 8 of Cycles 1 and 2, Day 1 of Cycles 3 to 16.
Mean Change From Baseline for European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (EORTC QLQ-C30) - Arm B Expansion
European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (EORTC QLQ-C30): included functional scales (physical, role, cognitive, emotional, and social), global health status, symptom scales (fatigue, pain, nausea/vomiting) and single items (dyspnoea, appetite loss, insomnia, constipation/diarrhea and financial difficulties). Most questions used 4 point scale (1 'Not at all' to 4 'Very much'; 2 questions used 7-point scale (1 'very poor' to 7 'Excellent'). Scores averaged, transformed to 0-100 scale; higher score=better level of functioning or greater degree of symptoms.
Measured: Baseline, Day 1 and Day 8 of Cycles 1 and 2, Day 1 of Cycles 3 to 16.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Aug 2013 (estimated)
- Study start10 Sep 2013
- Primary completion8 Jan 2020
- Study completion8 Jan 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for NeoplasmStudies of the same condition, open and under way.
- More trials run by PfizerThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 110 participants (actual)
Sponsor and investigators
- Lead sponsor
- Pfizer
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Pfizer CT.gov Call Center, Study director, Pfizer
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01920061
- Sponsor's protocol ID
- B2151002
- Other IDs
- 2013-001390-24
- Status last verified
- Aug 2022
- First submitted
- 7 Aug 2013
- Last updated
- 13 Sep 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- No: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical\_trials/trial\_data\_and\_results/data\_requests.
Publications
Curigliano G, Shapiro GI, Kristeleit RS, Abdul Razak AR, Leong S, Alsina M, Giordano A, Gelmon KA, Stringer-Reasor E, Vaishampayan UN, Middleton M, Olszanski AJ, Rugo HS, Kern KA, Pathan N, Perea R, Pierce KJ, Mutka SC, Wainberg ZA. A Phase 1B open-label study of gedatolisib (PF-05212384) in combination with other anti-tumour agents for patients with advanced solid tumours and triple-negative breast cancer. Br J Cancer. 2023 Jan;128(1):30-41. doi: 10.1038/s41416-022-02025-9. Epub 2022 Nov 5.
PubMed 36335217
Study at a glance
From the registry record, last updated by the sponsor on 13 Sep 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A PHASE 1B OPEN-LABEL THREE-ARM MULTI-CENTER STUDY TO ASSESS THE SAFETY AND TOLERABILITY OF PF-05212384 (PI3K/MTOR INHIBITOR) IN COMBINATION WITH OTHER ANTI-TUMOR AGENTS
- ClinicalTrials.gov ID
- NCT01920061
- Acronym / sponsor ID
- B2151002
- Conditions
- Neoplasm
- Keywords
- Advanced cancer, solid tumors, PI3K, mTOR, PI3K/mTOR, metastatic, Triple Negative Breast Cancer (TNBC)
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 110 participants (actual)
- Lead sponsor
- PfizerIndustry (pharma, biotech, devices)
- Study start
- 10 Sep 2013 (actual)
- Primary completion
- 8 Jan 2020 (actual)
- Study completion
- 8 Jan 2020 (actual)
- First posted
- 9 Aug 2013 (estimated)
- Results
- Posted 7 Oct 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will evaluate PF-05212384 (gedatolisib) PI3K/mTOR inhibitor)) in combination with either docetaxel, cisplatin or dacomitinib in select advanced solid tumors. The study will assess the safety, pharmacokinetics and pharmacodynamics of these combinations in patients with advanced cancer in order to determine the maximum tolerated dose in each combination. The cisplatin combination expansion portion will evaluate the anti tumor activity of PF 05212384 plus cisplatin in patients with TNBC in 2 separate Arms (Arm 1 and Arm 2).
Study design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| Arm A | Experimental | Drug: PF-05212384 (gedatolisib), Drug: Docetaxel |
| Arm B | Experimental | Drug: PF-05212384 (gedatolisib), Drug: Cisplatin |
| Arm C | Experimental | Drug: PF-05212384 (gedatolisib), Drug: Dacomitinib |
| Expansion Arm 1 | Experimental | Drug: PF-05212384 (gedatolisib), Drug: Cisplatin |
| Expansion Arm 2 | Experimental | Drug: PF-05212384 (gedatolisib), Drug: Cisplatin |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Arm 1:Patients with TNBC with no prior cytotoxic chemotherapy therapy in the metastatic setting; Arm 2: Patients with TNBC and one or two prior cytotoxic therapies in the metastatic setting.
- Arm A: castrate resistant prostate cancer, advanced breast cancer, or non-small cell lunch cancer that are candidates for treatment with a docetaxel-based combination.
- Arm B: Urothelial transitional cell cancer, triple negative breast cancer, ovarian cancer or non small cell lunch cancer that are candidates for a cisplatin-based combination.
- Arm C: Her2+ breast cancer refractory to prior herceptin or lapatinib, her2+ esophagal-gastric cancer, head and neck squamous cell cancer, or non small cell lunch cancer that are candidates for treatment with a dacomitinib-based combination.
- Availability of archival tumor biopsy sample or willing to provide fresh biopsy if not available.
Key exclusion criteria (9 listed)
- Prior therapy for Cisplatin Combination Expansion:
- Patients with known symptomatic brain metastases.
- Chemotherapy, radiotherapy, biologics or investigational agent within 4 weeks of the lead-in dose.
- Major surgery within 4 weeks of the baseline disease assessments.
- >2 prior regimens containing cytotoxic chemotherapy in the metastatic setting.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PF-05212384 (gedatolisib)PF-05212384 weekly intravenous infusions starting at 90 mg/wk as a 3 week cycle | Drug | Arm A, Arm B, Arm C, Expansion Arm 1, Expansion Arm 2 |
| DocetaxelDocetaxel intravenous infusions once every 3 weeks starting at 75 mg/m^2 | Drug | Arm A |
| CisplatinCisplatin intravenous infusions once every 3 weeks starting at 75 mg/m^2 | Drug | Arm B, Expansion Arm 1, Expansion Arm 2 |
| DacomitinibDacomitinib to be taken orally as a continuous once daily regimen at a starting dose of 30 mg | Drug | Arm C |
Primary outcome
Number of Participants With Dose Limiting Toxicities (DLTs) - Arms A, B and C
Time frame: Up to 21 days
DLT was defined as any of the following adverse events (AEs) attributable to the combination: (1) hematologic: grade 4 neutropenia lasting >7 days; febrile neutropenia; grade >=3 neutropenia with infection; grade 3 thrombocytopenia with bleeding; grade 4 thrombocytopenia; (2) non-hematologic: grade >=2 pneumonitis; grade>=3 toxicities, except pneumonitis, and excluding those that had not been maximally treated; persistent, intolerable toxicities which resulted in the failure to deliver at least 3 of the 4 doses of PF-05212384 for Arms A and B or at least 3 of the 4 doses of PF-05212384 and 75% of dacomitinib for Arm C during the first cycle; the persistent, intolerable toxicities which result in delay of the start of the second cycle by more than 2 weeks relative to the scheduled start; in an asymptomatic participant, the grade 3 QTc prolongation persists after correction of any reversible causes.
Percentage of Participants With Objective Response - Arm B Expansion
Time frame: Cycle 1 Day 1 up to 18 months
Percentage of participants with objective response based on the assessment of confirmed complete response (CR) or confirmed partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST v1.1). Confirmed responses are those that persist on repeat imaging study at least 4 weeks after initial documentation of response. Per RECIST v1.1: CR was defined as complete disappearance of all target lesions and non-target disease, with the exception of nodal disease. All nodes, both target and non-target, must decrease to normal (short axis <10 mm) and no new lesions. PR was defined as >=30% decrease under baseline of the sum of diameters of all target lesions. The short axis was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. No unequivocal progression of non-target disease and no new lesions.
67 secondary outcomes
Number of Participants With Treatment-Emergent Adverse Events (All Causality) - Arms A, B, C and B Expansion
Time frame: From the first dose of study drugs up to 28 days after the last dose of study drugs. Maximum duration between first and last dose: 505 days for Arm A, 414 days for Arm B, 842 days for Arm C, 728 days for Arm B Expansion.
Number of Participants With Treatment-Emergent Adverse Events (Treatment Related) - Arms A, B, C and B Expansion
Time frame: From the first dose of study drugs up to 28 days after the last dose of study drugs. Maximum duration between first and last dose: 505 days for Arm A, 414 days for Arm B, 842 days for Arm C, 728 days for Arm B Expansion.
Number of Participants With Laboratory Abnormalities by Severity (All Cycles) - Hematology
Time frame: From the first dose of study drugs up to 28 days after the last dose of study drugs. Maximum duration between first and last dose: 505 days for Arm A, 414 days for Arm B, 842 days for Arm C, 728 days for Arm B Expansion.
Number of Participants With Laboratory Abnormalities by Severity (All Cycles) - Coagulation
Time frame: From the first dose of study drugs up to 28 days after the last dose of study drugs. Maximum duration between first and last dose: 505 days for Arm A, 414 days for Arm B, 842 days for Arm C, 728 days for Arm B Expansion.
Number of Participants With Laboratory Abnormalities by Severity (All Cycles) - Chemistry
Time frame: From the first dose of study drugs up to 28 days after the last dose of study drugs. Maximum duration between first and last dose: 505 days for Arm A, 414 days for Arm B, 842 days for Arm C, 728 days for Arm B Expansion.
Number of Participants With Laboratory Abnormalities by Severity (All Cycles) - Urinalysis
Time frame: From the first dose of study drugs up to 28 days after the last dose of study drugs. Maximum duration between first and last dose: 505 days for Arm A, 414 days for Arm B, 842 days for Arm C, 728 days for Arm B Expansion.
Number of Participants With Vital Signs Data Meeting Pre-defined Criteria
Time frame: From baseline up to follow up (at least 28 days and no more than 35 days after discontinuation of treatment). Maximum duration between first and last dose: 842 days.
Maximum Observed Plasma Concentration (Cmax) Following Single IV Infusion Dose of PF-05212384 Alone - Plasma PF-05212384 (Arms A, B and C)
Time frame: Pre-dose, 0.5, 1, 2, 4, 6, 24, 72, 96 and 168 hours post-dose 7 days prior to Cycle 1 Day 1 for Arms A and B; pre-dose, 0.5, 1, 2, 4, 6, 24, 72, 96 and 168 hours post-dose 14 days prior to Cycle 1 Day 1 for Arm C.
Maximum Observed Plasma Concentration (Cmax) Following Single IV Infusion Dose of PF-05212384 in Combination With Cisplatin - Plasma PF-05212384 (Arm B Expansion)
Time frame: Pre-dose, 0.5, 1, 2, 4, 6, 24, 72, 96 and 168 (predose Day 8) hours post-dose on Cycle 1 Day 1.
Maximum Observed Plasma Concentration (Cmax) Following Multiple IV Infusion Doses of PF-05212384 in Combination With Docetaxel- Plasma PF-05212384 (Arm A)
Time frame: Pre-dose, 0.5, 1, 2, 4, 6, 24, 72, 96 and 168 hours post-dose on Cycle 2 Day 1.
Maximum Observed Plasma Concentration (Cmax) Following Multiple IV Infusion Doses of PF-05212384 in Combination With Cisplatin - Plasma PF-05212384 (Arm B)
Time frame: Pre-dose, 0.5, 1, 2, 4, 6, 24, 72, 96 and 168 hours post-dose on Cycle 2 Day 1.
Maximum Observed Plasma Concentration (Cmax) Following Multiple IV Infusion Doses of PF-05212384 in Combination With Dacomitinib - Plasma PF-05212384 (Arm C)
Time frame: Pre-dose, 0.5, 1, 2, 4, 6, 24, 72, 96 and 168 hours post-dose on Cycle 2 Day 1.
Maximum Observed Plasma Concentration (Cmax) Following Multiple IV Infusion Doses of PF-05212384 in Combination With Cisplatin - Plasma PF-05212384 (Arm B Expansion)
Time frame: Pre-dose, 0.5, 1, 2, 4, 6, 24, 72, 96 and 168 (predose Day 8) hours post-dose on Cycle 2 Day 1.
Maximum Observed Plasma Concentration (Cmax) Following Single IV Infusion Dose of Docetaxel Alone- Plasma Docetaxel (Arm A)
Time frame: Pre-dose, 1, 1.5, 2, 4, 6, and 24 hours post-dose on Cycle 1 Day 1.
Maximum Observed Plasma Concentration (Cmax) Following Administration of Docetaxel IV Infusion in Combination With PF-05212384 - Plasma Docetaxel (Arm A)
Time frame: Pre-dose, 1, 1.5, 2, 4, 6, and 24 hours post-dose on Cycle 2 Day 1.
Maximum Observed Plasma Concentration (Cmax) Following Single IV Infusion Dose of Cisplatin Alone - Plasma Platinum (Arm B)
Time frame: Pre-dose, 2, 2.5, 3, 4, 6, and 24 hours post-dose on Cycle 1 Day 1.
Maximum Observed Plasma Concentration (Cmax) Following Administration of Cisplatin IV Infusion in Combination With PF-05212384 - Plasma Platinum (Arm B)
Time frame: Pre-dose, 2, 2.5, 3, 4, 6, and 24 hours post-dose on Cycle 2 Day 1.
Maximum Observed Plasma Concentration (Cmax) Following Multiple Oral Doses of Dacomitinib Alone - Plasma Dacomitinib (Arm C)
Time frame: Pre-dose, 1, 2, 4, 6, and 24 hours post-dose on Cycle 1 Day 1.
Maximum Observed Plasma Concentration (Cmax) Following Multiple Oral Doses of Dacomitinib in Combination With PF-05212384 - Plasma Dacomitinib (Arm C)
Time frame: Pre-dose, 1, 2, 4, 6, and 24 hours post-dose on Cycle 2 Day 1.
Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) Following Single IV Infusion Dose of PF-05212384 Alone - Plasma PF-05212384 (Arms A, B and C)
Time frame: Pre-dose, 0.5, 1, 2, 4, 6, 24, 72, 96 and 168 hours post-dose 7 days prior to Cycle 1 Day 1 for Arms A and B; pre-dose, 0.5, 1, 2, 4, 6, 24, 72, 96 and 168 hours post-dose 14 days prior to Cycle 1 Day 1 for Arm C.
Area Under the Concentration-time Profile From Time 0 to Time Tau (AUCtau) Following Multiple IV Infusion Doses of PF-05212384 in Combination With Docetaxel- Plasma PF-05212384 (Arm A)
Time frame: Pre-dose, 0.5, 1, 2, 4, 6, 24, 72, 96 and 168 hours post-dose on Cycle 2 Day 1.
Area Under the Concentration-time Profile From Time 0 to Time Tau (AUCtau) Following Multiple IV Infusion Doses of PF-05212384 in Combination With Cisplatin - Plasma PF-05212384 (Arm B)
Time frame: Pre-dose, 0.5, 1, 2, 4, 6, 24, 72, 96 and 168 hours post-dose 7 days prior to Cycle 2 Day 1.
Area Under the Concentration-time Profile From Time 0 to Time Tau (AUCtau) Following Multiple IV Infusion Doses of PF-05212384 in Combination With Dacomitinib - Plasma PF-05212384 (Arm C)
Time frame: Pre-dose, 0.5, 1, 2, 4, 6, 24, 72, 96 and 168 hours post-dose on Cycle 2 Day 1.
Area Under the Concentration-time Profile From Time 0 to Time Tau (AUCtau) Following Single IV Infusion Dose of PF-05212384 in Combination With Cisplatin - Plasma PF-05212384 (Arm B Expansion)
Time frame: Pre-dose, 0.5, 1, 2, 4, 6, 24, 72, 96 and 168 (predose Day 8) hours post-dose on Cycle 1 Day 1.
Area Under the Concentration-time Profile From Time 0 to Time Tau (AUCtau) Following Multiple IV Infusion Doses of PF-05212384 in Combination With Cisplatin - Plasma PF-05212384 (Arm B Expansion)
Time frame: Pre-dose, 0.5, 1, 2, 4, 6, 24, 72, 96 and 168 (predose Day 8) hours post-dose on Cycle 2 Day 1.
Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) Following Single IV Infusion Dose of Docetaxel Alone- Plasma Docetaxel (Arm A)
Time frame: Pre-dose, 1, 1.5, 2, 4, 6, and 24 hours post-dose on Cycle 1 Day 1.
Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) Following Administration of Docetaxel in Combination With PF-05212384 - Plasma Docetaxel (Arm A)
Time frame: Pre-dose, 1, 1.5, 2, 4, 6, and 24 hours post-dose on Cycle 2 Day 1.
Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) Following Single IV Infusion Dose of Cisplatin Alone - Plasma Platinum (Arm B)
Time frame: Pre-dose, 2, 2.5, 3, 4, 6, and 24 hours post-dose on Cycle 1 Day 1.
Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) Following Administration of Cisplatin IV Infusion in Combination With PF-05212384 - Plasma Platinum (Arm B)
Time frame: Pre-dose, 2, 2.5, 3, 4, 6, and 24 hours post-dose on Cycle 2 Day 1.
Area Under the Concentration-time Profile From Time 0 to Time Tau (AUCtau) Following Multiple Oral Doses of Dacomitinib Alone - Plasma Dacomitinib (Arm C)
Time frame: Pre-dose, 1, 2, 4, 6, and 24 hours post-dose on Cycle 1 Day 1.
Area Under the Concentration-time Profile From Time 0 to Time Tau (AUCtau) Following Multiple Oral Doses of Dacomitinib in Combination With PF-05212384 - Plasma Dacomitinib (Arm C)
Time frame: Pre-dose, 1, 2, 4, 6, and 24 hours post-dose on Cycle 2 Day 1.
Time to Reach Maximum Observed Plasma Concentration (Tmax) Following Single IV Infusion Dose of PF-05212384 Alone - Plasma PF-05212384 (Arms A, B and C)
Time frame: Pre-dose, 0.5, 1, 2, 4, 6, 24, 72, 96 and 168 hours post-dose 7 days prior to Cycle 1 Day 1 for Arms A and B; pre-dose, 0.5, 1, 2, 4, 6, 24, 72, 96 and 168 hours post-dose 14 days prior to Cycle 1 Day 1 for Arm C.
Time to Reach Maximum Observed Plasma Concentration (Tmax) Following Multiple IV Infusion Doses of PF-05212384 in Combination With Docetaxel- Plasma PF-05212384 (Arm A)
Time frame: Pre-dose, 0.5, 1, 2, 4, 6, 24, 72, 96 and 168 hours post-dose on Cycle 2 Day 1.
Time to Reach Maximum Observed Plasma Concentration (Tmax) Following Multiple IV Infusion Doses of PF-05212384 in Combination With Cisplatin - Plasma PF-05212384 (Arm B)
Time frame: Pre-dose, 0.5, 1, 2, 4, 6, 24, 72, 96 and 168 hours post-dose on Cycle 2 Day 1.
Time to Reach Maximum Observed Plasma Concentration (Tmax) Following Multiple IV Infusion Doses of PF-05212384 in Combination With Dacomitinib - Plasma PF-05212384 (Arm C)
Time frame: Pre-dose, 0.5, 1, 2, 4, 6, 24, 72, 96 and 168 hours post-dose on Cycle 2 Day 1.
Time to Reach Maximum Observed Plasma Concentration (Tmax) Following Single IV Infusion Dose of Docetaxel Alone- Plasma Docetaxel (Arm A)
Time frame: Pre-dose, 1, 1.5, 2, 4, 6, and 24 hours post-dose on Cycle 1 Day 1.
Time to Reach Maximum Observed Plasma Concentration (Tmax) Following Administration of Docetaxel IV Infusion in Combination With PF-05212384 - Plasma Docetaxel (Arm A)
Time frame: Pre-dose, 1, 1.5, 2, 4, 6, and 24 hours post-dose on Cycle 2 Day 1.
Time to Reach Maximum Observed Plasma Concentration (Tmax) Following Single IV Infusion Dose of Cisplatin Alone - Plasma Platinum (Arm B)
Time frame: Pre-dose, 2, 2.5, 3, 4, 6, and 24 hours post-dose on Cycle 1 Day 1.
Time to Reach Maximum Observed Plasma Concentration (Tmax) Following Administration of Cisplatin IV Infusion in Combination With PF-05212384 - Plasma Platinum (Arm B)
Time frame: Pre-dose, 2, 2.5, 3, 4, 6, and 24 hours post-dose on Cycle 2 Day 1.
Time to Reach Maximum Observed Plasma Concentration (Tmax) Following Multiple Oral Doses of Dacomitinib Alone - Plasma Dacomitinib (Arm C)
Time frame: Pre-dose, 1, 2, 4, 6, and 24 hours post-dose on Cycle 1 Day 1.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Sep 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 36335217Curigliano G, Shapiro GI, Kristeleit RS, Abdul Razak AR, Leong S, Alsina M, Giordano A, Gelmon KA, Stringer-Reasor E, Vaishampayan UN, Middleton M, Olszanski AJ, Rugo HS, Kern KA, Pathan N, Perea R, Pierce KJ, Mutka SC, Wainberg ZA. A Phase 1B open-label study of gedatolisib (PF-05212384) in combination with other anti-tumour agents for patients with advanced solid tumours and triple-negative breast cancer. Br J Cancer. 2023 Jan;128(1):30-41. doi: 10.1038/s41416-022-02025-9. Epub 2022 Nov 5.
- To obtain contact information for a study center near you, click here.Link provided by the sponsor.
- Individual participant dataSharing planned: No. Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.
Related trials for Neoplasm
Not yet recruitingPhase 1
Hepatic Artery Infusion of Carfilzomib in Participants With Liver Metastatic Disease Previously Treated With Hepatic Artery Infusion Pump Therapy
Colorectal Neoplasms, Neoplasms
RecruitingPhase 2
Tafasitamab With Acalabrutinib and Venetoclax for the Treatment of Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
Chronic Lymphocytic Leukemia, Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
Active, not recruitingPhase 1/2
Selumetinib in Treating Young Patients With Recurrent or Refractory Low Grade Glioma
Low Grade Glioma, Recurrent Childhood Pilocytic Astrocytoma
Enrolling by invitationPhase 2
A Single-Arm Study of Nimotuzumab Combined With NALIRIFOX as First-Line Treatment for Pancreatic Cancer
Pancreatic Cancer Metastatic
Recruiting
Methylation Profiling in Self-Samples for Identification of (Epi)Genetic Biomarkers for Gynecological Cancers
Gynaecological Cancers, Ovarian Cancer
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Pfizer CT.gov Call Center study director
Pfizer
29 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing PF-05212384 (gedatolisib), Docetaxel and Cisplatin in people with Neoplasm, run by Pfizer at 29 sites in 5 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 13 Sep 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 29 sites in United States, Canada, Italy, Spain, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 7 Oct 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Dose Limiting Toxicities (DLTs) - Arms A, B and C (time frame: Up to 21 days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01920061, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Sep 2022.