Non-small Cell Lung CancerPhase 1/2NCT02393209
Docetaxel With or Without TAK-117 (MLN1117) in Participants With Locally Advanced or Metastatic Non-small Cell Lung Cancer
A Phase 1/2 study testing Docetaxel and TAK-117 in people with Non-small Cell Lung Cancer, run by Millennium Pharmaceuticals, Inc. at 11 sites in 3 countries.
Trial summary
The purpose of this study is to determine the recommended phase 2 dose (RP2D) of TAK-117 when administered in combination with docetaxel in participants with non-small cell lung cancer (NSCLC) and to evaluate efficacy, safety, and tolerability of TAK-117 administered alone and in combination with docetaxel at the RP2D… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Non-small Cell Lung Cancer
- What is being tested?
- Docetaxel and TAK-117
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 14 participants
- Where
- 11 sitesin 3 countries
- Study dates
- 3 Jun 2015to 20 Jan 2017
- Phase
- Phase 1/2
- 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
- Has a histologically and/or cytologically confirmed diagnosis of NSCLC (squamous or nonsquamous).
- For Phase 2 of the study, has a diagnosis of mixed squamous and nonsquamous (or adenosquamous) NSLC.
- Has locally advanced or metastatic disease (Stage IIIb or Stage IV) with radiographically or clinically evaluable lesions.
- Has experienced failure of at least 1 prior chemotherapy regimen:
- For Phase 2 of the study:
- Participants must have received 1 prior platinum-based chemotherapy regimen (excluding a docetaxel-containing regimen) for advanced or metastatic (Stage IIIb or Stage IV) disease followed by documented progressive disease (PD).
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- A drug provided as maintenance therapy following cytotoxic chemotherapy will be considered to be part of that regimen.
- Participants who received prior therapy with paclitaxel as a part of the platinum-based doublet front-line regimen without PD on therapy.
- Participants who, after the front-line, platinum-based, non-docetaxel containing chemotherapy, have been treated with 1 line of nivolumab or other immune-checkpoint inhibitors but progressed on or after the therapy.
- For Phase 1b of the study: Participants who have experienced failure of multiple lines of prior chemotherapy are eligible.
- For Phase 2, has archived or fresh tumor biopsy samples (obtained during screening) sufficient for genotyping.
- Has adequate organ function, before the first dose of study drug.
- Has Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.
- Female participants who are postmenopausal for at least 1 year before the screening visit or are surgically sterile, or are of childbearing potential, agree to practice 1 highly effective method and 1 additional effective (barrier) method of contraception, at the same time, from the time of signing the informed consent through 30 days (or longer, as mandated by local labeling) after the last dose of study drug, or agree to practice true abstinence.
- Female participants must agree to not donate eggs (ova) during the course of this study and for 30 days after receiving their last dose of TAK-117 and, for docetaxel, for as long as is mandated by local labeling.
- Male participants agree to practice highly effective barrier contraception during the entire study treatment period and through 120 days after the last dose of TAK-117 and, for docetaxel, for as long as is mandated by local labeling, or agree to practice true abstinence.
- Male participants must agree to not donate sperm during the course of the study and for 120 days after receiving their last dose of TAK-117 and, for docetaxel, for as long as is mandated by local labeling.
- Has suitable venous access for the study-required blood sampling.
- Has recovered (ie, <= Grade 1 toxicity or eligibility per this protocol is met) from the reversible effects of prior anticancer therapy.
- In the opinion of the investigator, the participant or legal guardian is capable of understanding and complying with protocol requirements for the duration of the study.
Who cannot join
- Previous treatment with a PI3K or AKT inhibitor.
- Prior cancer therapy or other investigational therapy within 2 weeks before the first administration of study drug or failed to recover from the reversible effects of prior anticancer therapies. For prior therapies with a half-life longer than 3 days, the interval must be at least 28 days before the first administration of study drug, and the participant must have documented progressive disease.
- Has poorly controlled diabetes mellitus defined as HbA1c > 6.5%.
- Has taken strong inhibitors or strong inducers of CYP3A4 within 14 days before the first dose of study drug.
- Has taken histamine-H2 receptor antagonists and/or neutralizing antacids within 24 hours before the first administration of study drug.
- Has taken proton pump inhibitors within 7 days before the first administration of study drug.
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- Has a condition that requires the concomitant use of any of the protocol-excluded medications, supplements, or food products during the course of the study .
- Has any clinically significant co-morbidities.
- Has acute myocardial infarction within 6 months before starting study drug, current or history of New York Heart Association Class III or IV heart failure; evidence of current uncontrolled cardiovascular conditions including cardiac arrhythmias, angina, pulmonary hypertension, or electrocardiogram (ECG) evidence of acute ischemia or active conduction system abnormalities; Fridericia's corrected QT interval > 475 milliseconds (msec) (males) or > 450 msec (females) on a 12-lead ECG during the Screening period; or abnormalities on 12-lead ECG including, but not limited to, changes in rhythm and intervals that in the opinion of the investigator are considered to be clinically significant.
- Has known, previously diagnosed human immunodeficiency virus infection or active chronic hepatitis B or C.
- Has brain metastasis, unless has completed definitive therapy, is not on steroids, has a stable neurologic status for at least 2 weeks after completion of the definitive therapy and steroids, and does not have neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.
- Has active secondary malignancy that requires treatment.
- Has any serious medical or psychiatric illness, including drug or alcohol abuse.
- Male participants who intend to donate sperm during the course of this study or 120 days after receiving their last dose of TAK-117 and, for docetaxel, for as long as is mandated by local labeling.
- Female participants who are lactating and breastfeeding or have a positive serum pregnancy test during the Screening period or a positive urine pregnancy test on Day 1 before administration of the first dose of study drug.
- Is unwilling or unable to abide by the requirements of the study.
Trial locations and contacts
11 sites in 3 countries.
11 sites in 3 countries
United States6 sites
Study site
Atlanta, Georgia
Study site
Chattanooga, Tennessee
Study site
Farmington Hills, Michigan
Study site
Rochester, Minnesota
Study site
San Diego, California
Study site
St Louis, Missouri
Netherlands3 sites
Study site
Amsterdam
Study site
Hoofddorp
Study site
Maastricht
About this study
Official title: A Phase 1b/Adaptive Phase 2 Study of Docetaxel With or Without MLN1117 in Patients With Locally Advanced or Metastatic Non-small Cell Lung Cancer
The purpose of this study is to determine the recommended phase 2 dose (RP2D) of TAK-117 when administered in combination with docetaxel in participants with non-small cell lung cancer (NSCLC) and to evaluate efficacy, safety, and tolerability of TAK-117 administered alone and in combination with docetaxel at the RP2D in participants with locally advanced or metastatic non-small cell lung cancer.
Read the detailed description
The drug being evaluated in this study is called TAK-117. TAK-117 is tested in combination with docetaxel versus docetaxel alone for the treatment of non-small cell lung cancer (NSCLC).
This study consisted of 2 phases:
- Phase 1b - dose escalation phase
- Phase 2 - expansion phase.
The study enrolled 14 patients with NSCLC who have been treated with multiple prior lines of therapies will be enrolled for Phase 1b. The participants will receive docetaxel (36 mg/m^2) intravenous (IV) and TAK-117 tablets, orally administered, once daily in 21-day dosing cycles. The TAK-117 dose will be escalated until recommended Phase 2 dose (RP2D) is determined.
Each part of the adaptive Phase 2 portion of the study is designed as a stand-alone, randomized study evaluating PFS as the primary efficacy measure in a total of 60 participants between the 2 treatment arms: TAK-117 plus docetaxel versus docetaxel alone. An event-driven analysis of PFS will be performed after each part of Phase 2. On the basis of the PFS analysis of the preceding part of the study, the study may be stopped for efficacy or futility, or proceed to the next part. However, Phase 2 of the study was cancelled.
Study drug will be administered in 21-day dosing cycles. During each phase of the study, participants will be treated with a maximum of 9 cycles of either docetaxel alone or docetaxel plus TAK-117. Subsequently, participants treated with docetaxel plus TAK-117 may continue to receive TAK-117 monotherapy until progression of disease, occurrence of unacceptable toxicities or death.
The maximum duration of treatment for participants will be 12 months unless it is determined that a participant would derive benefit from continued treatment beyond 12 months. Participants will continue to be followed after discontinuation of study drug to collect PFS and OS data. Participants may withdraw from therapy at any time.
This multicenter trial will be conducted in North America. The overall time to participate in this study is up to 24 months.
- Conditions
- Non-small Cell Lung Cancer
- Being tested
- Docetaxel, TAK-117
- Keywords
- Drug therapy
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DocetaxelDrug
Docetaxel intravenous infusion
TAK-117Drug
Also called MLN1117
TAK-117 Tablets
| Study group | Role | What they receive |
|---|---|---|
| TAK-117 200 mg + Docetaxel (36 mg/m^2) | Experimental | TAK-117 200 mg, tablets, orally on Days 2, 3, 4, 9, 10, 11, 16, 17, and 18 of the 21-day cycle and docetaxel 36 mg/m^2, intravenous (IV) infusion, on Days 1 and 8 of the 21-day cycle up ro Cycle 9 (approximately 189 days). Receives: Drug: Docetaxel; Drug: TAK-117 |
| TAK-117 300 mg + Docetaxel 36 mg/m^2 | Experimental | TAK-117 200 mg, tablets, orally on Days 2, 3, 4, 9, 10, 11, 16, 17, and 18 of the 21-day cycle and docetaxel 36 mg/m^2, IV infusion, on Days 1 and 8 of the 21-day cycle up to 6 cycles (approximately 126 days). Receives: Drug: Docetaxel; Drug: TAK-117 |
| Phase 2 - TAK-117 + Docetaxel 36 mg/m^2 | Experimental | TAK-117 tablets, at the dose determined in the dose escalation phase, on Days 2, 3, 4, 9, 10, 11, 16, 17, and 18 of a 21-day cycle plus Docetaxel 36 mg/m^2 IV infusion on Days 1 and 8 of a 21-day cycle. Receives: Drug: Docetaxel; Drug: TAK-117 |
| Phase 2 - Docetaxel 75 mg/m^2 | Experimental | Docetaxel 75 mg/m^2, IV infusion once every 3 weeks (per approved prescribing information) with dosing on Day 1 of each 21-day cycle. Receives: Drug: Docetaxel; Drug: TAK-117 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Dose-Limiting Toxicity (DLT) in Phase 1b
DLT was evaluated according to National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03 and was defined as any of the following events: 1. Grade 4 neutropenia or thrombocytopenia lasting ≥7 consecutive days; 2. Grade 4 neutropenia with fever and/or infection; 3. Platelet count <10,000/mm^3; 4. ≥Grade 3 thrombocytopenia with bleeding; 5. Any other ≥Grade 4 hematologic toxicity; 6. Any other ≥Grade 3 nonhematologic toxicity, with following exceptions: ≥Grade 3 arthralgia/myalgia, ≥Grade 3 nausea/emesis, ≥Grade 3 diarrhoea, Grade 3 fatigue, Grade 3 Rash, Grade 3 nonhematological toxicity that could be controlled to ≤Grade 1 with appropriate treatment; 7. Inability to administer at least 75% of planned doses; 8. Clinically significant occurrence per investigator that is a safety risk.
Measured: Cycle 1 (Up to Day 21)
Maximum Tolerated Dose (MTD) of TAK-117 in Combination With Docetaxel 36 mg/m^2 in Phase 1b
The MTD is defined as the dose of TAK-117 in combination with docetaxel 36 mg/m^2 at which 1 of 6 evaluable participants experience DLT. DLT was evaluated according to NCI CTCAE version 4.03 and was defined as any of the following events: 1. Grade 4 neutropenia or thrombocytopenia lasting ≥7 consecutive days; 2. Grade 4 neutropenia with fever and/or infection; 3. Platelet count <10,000/mm^3; 4. ≥Grade 3 thrombocytopenia with bleeding; 5. Any other ≥Grade 4 hematologic toxicity; 6. Any other ≥Grade 3 nonhematologic toxicity, with following exceptions: ≥Grade 3 arthralgia/myalgia, ≥Grade 3 nausea/emesis, ≥Grade 3 diarrhoea, Grade 3 fatigue, Grade 3 Rash, Grade 3 nonhematological toxicity that could be controlled to ≤Grade 1 with appropriate treatment; 7. Inability to administer at least 75% of planned doses; 8. Clinically significant occurrence per investigator that is a safety risk.
Measured: Cycle 1 (Up to Day 21)
Recommended Phase 2 Dose of TAK-117 in Phase 1b
The recommended phase 2 dose was determined in Phase 1b based on participant dose-limiting toxicities and the maximum tolerated dose.
Measured: Cycle 1 (Up to Day 21)
Progression-Free Survival (PFS) in Phase 2
PFS is defined as the time from the date randomization to the date of first documented progressive disease (PD) or death as assessed by the investigator using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 criteria. PD is defined as 20% increase in the sum of the longest diameter of target lesions for measurable neoplastic disease.
Measured: Approximately 12 months in Phase 2
Secondary outcomes (23)
Number of Participants With Significant Change in Vital Signs Reported as Adverse Events in Phase 1b
Clinically significant change from baseline in vital sign measures will be assessed. Vital sign measurements included measurements of diastolic and systolic blood pressure, heart rate, and temperature.
Measured: First dose of study drug through 30 days after the last dose of study drug (Up to Day 223)
Number of Participants With Significant Change in Physical Examination Reported as Adverse Events in Phase 1b
Physical examination consists of examinations of the following body systems: (1) eyes; (2) ears, nose, throat; (3) cardiovascular system; (4) respiratory system; (5) gastrointestinal system; (6) dermatologic system; (7) extremities; (8) musculoskeletal system; (9) nervous system; (10) lymph nodes; and (11) physical examinations other than body systems described in (1) to (10).
Measured: First dose of study drug through 30 days after the last dose of study drug (Up to Day 223)
Number of Participants With Electrocardiogram (ECG) Findings Reported as Adverse Events in Phase 1b
A standard 12-lead ECG was performed.
Measured: First dose of study drug through 30 days after the last dose of study drug (Up to Day 223)
Number of Participants With Clinically Significant Change in Clinical Laboratory Tests Reported as Adverse Events in Phase 1b
The number of participants with any markedly abnormal standard safety laboratory values (Chemistry, Hematology and Urinalysis) collected throughout study.
Measured: First dose of study drug through 30 days after the last dose of study drug (Up to Day 223)
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) in Phase 1b
An Adverse Event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. A treatment-emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug. A serious adverse event (SAE) is any untoward medical occurrence or effect that at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability / incapacity, is a congenital anomaly / birth defect or is medically important due to other reasons than the above mentioned criteria. A treatment-emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug.
Measured: From first dose of study drug to 30 days after last dose of study drug (Up to Day 223)
Number of Participants With Significant Change in Vital Signs Reported as Adverse Events in Phase 2
Vital signs (blood pressure, pulse rate, and oral temperature) measurements were collected throughout the study.
Measured: Approximately 12 months in Phase 2
Number of Participants With Significant Change in Physical Examination Reported as Adverse Events in Phase 2
Physical examination consists of examinations of the following body systems: (1) eyes; (2) ears, nose, throat; (3) cardiovascular system; (4) respiratory system; (5) gastrointestinal system; (6) dermatologic system; (7) extremities; (8) musculoskeletal system; (9) nervous system; (10) lymph nodes; and (11) physical examinations other than body systems described in (1) to (10).
Measured: Approximately 12 months in Phase 2
Number of Participants With Electrocardiogram (ECG) Findings Reported as Adverse Events in Phase 2
Clinically significant changes from baseline in ECGs will be tabulated by time point including any unscheduled measurements.
Measured: Approximately 12 months in Phase 2
Number of Participants With Clinically Significant Change in Clinical Laboratory Tests Reported as Adverse Events in Phase 2
The number of participants with any markedly abnormal standard safety laboratory values (Chemistry, Hematology and Urinalysis) collected throughout study.
Measured: Approximately 12 months in Phase 2
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) in Phase 2
An Adverse Event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. A treatment-emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug. A serious adverse event (SAE) is any untoward medical occurrence or effect that at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability / incapacity, is a congenital anomaly / birth defect or is medically important due to other reasons than the above mentioned criteria. A treatment-emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug.
Measured: Approximately 12 months in Phase 2
Response Rate in Phase 2
Response rate is defined as the percentage of participants with Complete Response (CR) + Partial Response (PR) as assessed by the investigator according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria 1.1. According to RECIST: CR is defined as disappearance of all target lesions and PR is defined as 30% decrease in the sum of the longest diameter of target lesions.
Measured: Approximately 12 months in Phase 2
Disease Control Rate in Phase 2
Disease control rate is defined as percentage of participants with CR + PR + stable disease (SD). According to RECIST: CR is defined as disappearance of all target lesions, PR is defined as 30% decrease in the sum of the longest diameter of target lesions and SD is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum longest diameter (LD) since the treatment started.
Measured: Approximately 12 months in Phase 2
Duration of Response in Phase 2
The duration of response is defined as the time from the date of first documentation of a response to the date of first documentation of progression of disease. As per RECIST 1.1, PD is defined as 20% increase in the sum of the longest diameter of target lesions for measurable neoplastic disease.
Measured: Approximately 12 months in Phase 2
Time to Progression in Phase 2
Time to progression is defined as the time from the date of randomization to the date of first documentation of progression of disease. As per RECIST 1.1, PD is defined as 20% increase in the sum of the longest diameter of target lesions for measurable neoplastic disease.
Measured: Approximately 12 months in Phase 2
Overall Survival (OS) in Phase 2
Overall survival is defined as the time from the date of randomization to the date of death.
Measured: Approximately 12 months in Phase 2
TAK-117 Plasma Concentration in Phase 1b
Measured: Cycle 1 Day 1 pre-dose and 0.5, 1, 2, 4, 6, 8 and 24 hours post-dose
Cmax: Maximum Observed Plasma Concentration for TAK-117
Measured: Cycle 1 Day 1 pre-dose and 0.5, 1, 2, 4, 6, 8 and 24 hours post-dose
Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-117
Measured: Cycle 1 Day 1 pre-dose and up to 24 hours post-dose
AUCtau: Area Under the Concentration Time Curve From Time 0 to the Next Dose in Phase 1b for TAK-117
Measured: Cycle 1 Day 1 pre-dose and up to 24 hours post-dose
AUC(Last): Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration in Phase 1b for TAK-117
Measured: Cycle 1 Day 1 pre-dose and up to 24 hours post-dose
CL/F: Oral Clearance for TAK-117
Measured: Cycle 1 Day 1 pre-dose and up to 24 hours post-dose
T1/2: Terminal Phase Elimination Half-life (T1/2) for TAK-117
Measured: Cycle 1 Day 1 pre-dose and up to 24 hours post-dose
TAK-117 Plasma Concentrations When Administered 1 Day After Docetaxel in Phase 2
Measured: 1 day post docetaxel dose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Mar 2015 (estimated)
- Study start3 Jun 2015
- Primary completion12 Jan 2017
- Study completion20 Jan 2017
Why it stopped: Lack of efficacy in combination.
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.
- Other trials for Non-small Cell Lung CancerStudies of the same condition, open and under way.
- 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 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 14 participants (actual)
Sponsor and investigators
- Lead sponsor
- Millennium Pharmaceuticals, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Director Clinical Science, Study director, Millennium Pharmaceuticals, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02393209
- Sponsor's protocol ID
- MLN1117-1501
- Other IDs
- 2014-004281-25, U1111-1160-1736, 2014
- Status last verified
- Jan 2018
- First submitted
- 15 Mar 2015
- Last updated
- 7 Feb 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 7 Feb 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1b/Adaptive Phase 2 Study of Docetaxel With or Without MLN1117 in Patients With Locally Advanced or Metastatic Non-small Cell Lung Cancer
- ClinicalTrials.gov ID
- NCT02393209
- Acronym / sponsor ID
- MLN1117-1501
- Conditions
- Non-small Cell Lung Cancer
- Keywords
- Drug therapy
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Lack of efficacy in combination.
- Enrolment
- 14 participants (actual)
- Lead sponsor
- Millennium Pharmaceuticals, Inc.Industry (pharma, biotech, devices)
- Study start
- 3 Jun 2015 (actual)
- Primary completion
- 12 Jan 2017 (actual)
- Study completion
- 20 Jan 2017 (actual)
- First posted
- 19 Mar 2015 (estimated)
- Results
- Posted 7 Feb 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to determine the recommended phase 2 dose (RP2D) of TAK-117 when administered in combination with docetaxel in participants with non-small cell lung cancer (NSCLC) and to evaluate efficacy, safety, and tolerability of TAK-117 administered alone and in combination with docetaxel at the RP2D in participants with locally advanced or metastatic non-small cell lung cancer.
Detailed description
The drug being evaluated in this study is called TAK-117. TAK-117 is tested in combination with docetaxel versus docetaxel alone for the treatment of non-small cell lung cancer (NSCLC).
This study consisted of 2 phases:
- Phase 1b - dose escalation phase
- Phase 2 - expansion phase.
The study enrolled 14 patients with NSCLC who have been treated with multiple prior lines of therapies will be enrolled for Phase 1b. The participants will receive docetaxel (36 mg/m^2) intravenous (IV) and TAK-117 tablets, orally administered, once daily in 21-day dosing cycles. The TAK-117 dose will be escalated until recommended Phase 2 dose (RP2D) is determined.
Each part of the adaptive Phase 2 portion of the study is designed as a stand-alone, randomized study evaluating PFS as the primary efficacy measure in a total of 60 participants between the 2 treatment arms: TAK-117 plus docetaxel versus docetaxel alone. An event-driven analysis of PFS will be performed after each part of Phase 2. On the basis of the PFS analysis of the preceding part of the study, the study may be stopped for efficacy or futility, or proceed to the next part. However, Phase 2 of the study was cancelled.
Study drug will be administered in 21-day dosing cycles. During each phase of the study, participants will be treated with a maximum of 9 cycles of either docetaxel alone or docetaxel plus TAK-117. Subsequently, participants treated with docetaxel plus TAK-117 may continue to receive TAK-117 monotherapy until progression of disease, occurrence of unacceptable toxicities or death.
The maximum duration of treatment for participants will be 12 months unless it is determined that a participant would derive benefit from continued treatment beyond 12 months. Participants will continue to be followed after discontinuation of study drug to collect PFS and OS data. Participants may withdraw from therapy at any time.
This multicenter trial will be conducted in North America. The overall time to participate in this study is up to 24 months.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| TAK-117 200 mg + Docetaxel (36 mg/m^2) | Experimental | Drug: Docetaxel, Drug: TAK-117TAK-117 200 mg, tablets, orally on Days 2, 3, 4, 9, 10, 11, 16, 17, and 18 of the 21-day cycle and docetaxel 36 mg/m^2, intravenous (IV) infusion, on Days 1 and 8 of the 21-day cycle up ro Cycle 9 (approximately 189 days). |
| TAK-117 300 mg + Docetaxel 36 mg/m^2 | Experimental | Drug: Docetaxel, Drug: TAK-117TAK-117 200 mg, tablets, orally on Days 2, 3, 4, 9, 10, 11, 16, 17, and 18 of the 21-day cycle and docetaxel 36 mg/m^2, IV infusion, on Days 1 and 8 of the 21-day cycle up to 6 cycles (approximately 126 days). |
| Phase 2 - TAK-117 + Docetaxel 36 mg/m^2 | Experimental | Drug: Docetaxel, Drug: TAK-117TAK-117 tablets, at the dose determined in the dose escalation phase, on Days 2, 3, 4, 9, 10, 11, 16, 17, and 18 of a 21-day cycle plus Docetaxel 36 mg/m^2 IV infusion on Days 1 and 8 of a 21-day cycle. |
| Phase 2 - Docetaxel 75 mg/m^2 | Experimental | Drug: Docetaxel, Drug: TAK-117Docetaxel 75 mg/m^2, IV infusion once every 3 weeks (per approved prescribing information) with dosing on Day 1 of each 21-day cycle. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (20 listed)
- Has a histologically and/or cytologically confirmed diagnosis of NSCLC (squamous or nonsquamous).
- Has locally advanced or metastatic disease (Stage IIIb or Stage IV) with radiographically or clinically evaluable lesions.
- Has experienced failure of at least 1 prior chemotherapy regimen:
- Has adequate organ function, before the first dose of study drug.
- Has Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.
Key exclusion criteria (16 listed)
- Previous treatment with a PI3K or AKT inhibitor.
- Prior cancer therapy or other investigational therapy within 2 weeks before the first administration of study drug or failed to recover from the reversible effects of prior anticancer therapies. For prior therapies with a half-life longer than 3 days, the interval must be at least 28 days before the first administration of study drug, and the participant must have documented progressive disease.
- Has poorly controlled diabetes mellitus defined as HbA1c > 6.5%.
- Has taken strong inhibitors or strong inducers of CYP3A4 within 14 days before the first dose of study drug.
- Has taken histamine-H2 receptor antagonists and/or neutralizing antacids within 24 hours before the first administration of study drug.
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 |
|---|---|---|
| DocetaxelDocetaxel intravenous infusion | Drug | Phase 2 - Docetaxel 75 mg/m^2, Phase 2 - TAK-117 + Docetaxel 36 mg/m^2, TAK-117 200 mg + Docetaxel (36 mg/m^2), TAK-117 300 mg + Docetaxel 36 mg/m^2 |
| TAK-117Also: MLN1117TAK-117 Tablets | Drug | Phase 2 - Docetaxel 75 mg/m^2, Phase 2 - TAK-117 + Docetaxel 36 mg/m^2, TAK-117 200 mg + Docetaxel (36 mg/m^2), TAK-117 300 mg + Docetaxel 36 mg/m^2 |
Primary outcome
Number of Participants With Dose-Limiting Toxicity (DLT) in Phase 1b
Time frame: Cycle 1 (Up to Day 21)
DLT was evaluated according to National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03 and was defined as any of the following events: 1. Grade 4 neutropenia or thrombocytopenia lasting ≥7 consecutive days; 2. Grade 4 neutropenia with fever and/or infection; 3. Platelet count <10,000/mm^3; 4. ≥Grade 3 thrombocytopenia with bleeding; 5. Any other ≥Grade 4 hematologic toxicity; 6. Any other ≥Grade 3 nonhematologic toxicity, with following exceptions: ≥Grade 3 arthralgia/myalgia, ≥Grade 3 nausea/emesis, ≥Grade 3 diarrhoea, Grade 3 fatigue, Grade 3 Rash, Grade 3 nonhematological toxicity that could be controlled to ≤Grade 1 with appropriate treatment; 7. Inability to administer at least 75% of planned doses; 8. Clinically significant occurrence per investigator that is a safety risk.
Maximum Tolerated Dose (MTD) of TAK-117 in Combination With Docetaxel 36 mg/m^2 in Phase 1b
Time frame: Cycle 1 (Up to Day 21)
The MTD is defined as the dose of TAK-117 in combination with docetaxel 36 mg/m^2 at which 1 of 6 evaluable participants experience DLT. DLT was evaluated according to NCI CTCAE version 4.03 and was defined as any of the following events: 1. Grade 4 neutropenia or thrombocytopenia lasting ≥7 consecutive days; 2. Grade 4 neutropenia with fever and/or infection; 3. Platelet count <10,000/mm^3; 4. ≥Grade 3 thrombocytopenia with bleeding; 5. Any other ≥Grade 4 hematologic toxicity; 6. Any other ≥Grade 3 nonhematologic toxicity, with following exceptions: ≥Grade 3 arthralgia/myalgia, ≥Grade 3 nausea/emesis, ≥Grade 3 diarrhoea, Grade 3 fatigue, Grade 3 Rash, Grade 3 nonhematological toxicity that could be controlled to ≤Grade 1 with appropriate treatment; 7. Inability to administer at least 75% of planned doses; 8. Clinically significant occurrence per investigator that is a safety risk.
Recommended Phase 2 Dose of TAK-117 in Phase 1b
Time frame: Cycle 1 (Up to Day 21)
The recommended phase 2 dose was determined in Phase 1b based on participant dose-limiting toxicities and the maximum tolerated dose.
Progression-Free Survival (PFS) in Phase 2
Time frame: Approximately 12 months in Phase 2
PFS is defined as the time from the date randomization to the date of first documented progressive disease (PD) or death as assessed by the investigator using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 criteria. PD is defined as 20% increase in the sum of the longest diameter of target lesions for measurable neoplastic disease.
23 secondary outcomes
Number of Participants With Significant Change in Vital Signs Reported as Adverse Events in Phase 1b
Time frame: First dose of study drug through 30 days after the last dose of study drug (Up to Day 223)
Number of Participants With Significant Change in Physical Examination Reported as Adverse Events in Phase 1b
Time frame: First dose of study drug through 30 days after the last dose of study drug (Up to Day 223)
Number of Participants With Electrocardiogram (ECG) Findings Reported as Adverse Events in Phase 1b
Time frame: First dose of study drug through 30 days after the last dose of study drug (Up to Day 223)
Number of Participants With Clinically Significant Change in Clinical Laboratory Tests Reported as Adverse Events in Phase 1b
Time frame: First dose of study drug through 30 days after the last dose of study drug (Up to Day 223)
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) in Phase 1b
Time frame: From first dose of study drug to 30 days after last dose of study drug (Up to Day 223)
Number of Participants With Significant Change in Vital Signs Reported as Adverse Events in Phase 2
Time frame: Approximately 12 months in Phase 2
Number of Participants With Significant Change in Physical Examination Reported as Adverse Events in Phase 2
Time frame: Approximately 12 months in Phase 2
Number of Participants With Electrocardiogram (ECG) Findings Reported as Adverse Events in Phase 2
Time frame: Approximately 12 months in Phase 2
Number of Participants With Clinically Significant Change in Clinical Laboratory Tests Reported as Adverse Events in Phase 2
Time frame: Approximately 12 months in Phase 2
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) in Phase 2
Time frame: Approximately 12 months in Phase 2
Response Rate in Phase 2
Time frame: Approximately 12 months in Phase 2
Disease Control Rate in Phase 2
Time frame: Approximately 12 months in Phase 2
Duration of Response in Phase 2
Time frame: Approximately 12 months in Phase 2
Time to Progression in Phase 2
Time frame: Approximately 12 months in Phase 2
Overall Survival (OS) in Phase 2
Time frame: Approximately 12 months in Phase 2
TAK-117 Plasma Concentration in Phase 1b
Time frame: Cycle 1 Day 1 pre-dose and 0.5, 1, 2, 4, 6, 8 and 24 hours post-dose
Cmax: Maximum Observed Plasma Concentration for TAK-117
Time frame: Cycle 1 Day 1 pre-dose and 0.5, 1, 2, 4, 6, 8 and 24 hours post-dose
Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-117
Time frame: Cycle 1 Day 1 pre-dose and up to 24 hours post-dose
AUCtau: Area Under the Concentration Time Curve From Time 0 to the Next Dose in Phase 1b for TAK-117
Time frame: Cycle 1 Day 1 pre-dose and up to 24 hours post-dose
AUC(Last): Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration in Phase 1b for TAK-117
Time frame: Cycle 1 Day 1 pre-dose and up to 24 hours post-dose
CL/F: Oral Clearance for TAK-117
Time frame: Cycle 1 Day 1 pre-dose and up to 24 hours post-dose
T1/2: Terminal Phase Elimination Half-life (T1/2) for TAK-117
Time frame: Cycle 1 Day 1 pre-dose and up to 24 hours post-dose
TAK-117 Plasma Concentrations When Administered 1 Day After Docetaxel in Phase 2
Time frame: 1 day post docetaxel dose
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Feb 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Medical Director Clinical Science study director
Millennium Pharmaceuticals, Inc.
11 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Docetaxel and TAK-117 in people with Non-small Cell Lung Cancer, run by Millennium Pharmaceuticals, Inc. at 11 sites in 3 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 20 inclusion and 16 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: stopped early, as of the sponsor's last update on 7 Feb 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 11 sites in United States, Netherlands, Canada. 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 combined 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.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 Feb 2018). 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 Toxicity (DLT) in Phase 1b (time frame: Cycle 1 (Up to Day 21)). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 7 Feb 2018.