Prostate CancerPhase 1/2NCT01511536
Cabazitaxel and Abiraterone Acetate in Patients With Metastatic Castrate-Resistant Prostate Cancer
A Phase 1/2 study testing Cabazitaxel XRP6258, Abiraterone acetate and Prednisone 5 mg in people with Prostate Cancer, run by Sanofi at 4 sites in 3 countries.
Trial summary
Primary Objectives: To determine the maximum tolerated dose, and dose limiting toxicities of cabazitaxel administered as a 1-hour infusion every 3 weeks in combination with oral daily abiraterone acetate and prednisone in participants with metastatic Castrate-resistant prostate cancer (CRPC) To estimate the anti-tumor… Read more about this study
- Who is it for?
- Ages 18 years and older, men only
- Conditions the study is for
- Prostate Cancer
- What is being tested?
- Cabazitaxel XRP6258, Abiraterone acetate and Prednisone 5 mg
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 38 participants
- Where
- 4 sitesin 3 countries
- Study dates
- Mar 2012to Dec 2014
- 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
- Men only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Diagnosis of prostate adenocarcinoma proven histologically or cytologically, resistant to hormone therapy and previously treated with a docetaxel-containing regimen. In Phase 2 part, participants should have been treated with abiraterone acetate for at least 3 months and should continue treatment with abiraterone acetate before study entry
- Presence of metastatic prostate cancer.
- Participant must had progressive disease documented by rising PSA defined as 2 sequential increases above a previous lowest reference value (each PSA value must be obtained at least 1 week apart. A PSA value of at least 6 ng/mL was required at study entry). In Phase 1 part, in addition to rising PSA, progressive disease must be documented by:
- Increase in non-measureable or measurable disease, and/or
- Appearance of new lesions, including those on bone scan (≥2 new lesions on 2 consecutive bone scans if progressive disease diagnosed on bone scan only) consistent with progressive prostate cancer
- Effective castration (serum testosterone levels ≤0.50 ng/mL) by orchiectomy and/or luteinizing hormone-releasing hormone agonists /antagonist.
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- If the participant had been treated with luteinizing hormone-releasing hormone agonists/antagonist (i.e., without orchiectomy), then this therapy had been initiated at least 4 weeks prior to cycle 1 day 1 and should be continued throughout the study.
- Prior anti-androgen therapy should be stopped before enrollment
- Eastern Cooperative Oncology Group performance status: 0 - 1.
Who cannot join
- Previous treatment with mitoxantrone or cabazitaxel.
- Prior bone-seeking radio-isotope therapy (participants treated with Radium223 were not excluded from the study). Radiotherapy to ≥30% of bone marrow.
- Adverse events from any prior anticancer therapy of grade >1 at the time of enrollment.
- Prior surgery, radiation, chemotherapy, or other anti-cancer therapy within 4 weeks prior to enrollment in the study (except luteinizing hormone-releasing hormone agonist /antagonist and abiraterone acetate in the Phase 2 part of the study); small field single fraction palliative radiation within 1 week.
- Prior malignancy. Curatively treated basal cell or squamous cell skin or superficial (pTis, pTa, and pT1) bladder cancer were allowed, as well as any other cancer for which chemotherapy had been completed ≥ 3 years ago and from which the participant had been disease-free for ≥ 3 years.
- Participation in another clinical trial and any concurrent treatment with any investigational drug within 30 days prior to enrollment.
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- Known brain or leptomeningeal metastases.
- Any severe acute or chronic medical condition which could impair the ability of the participant to participate to the study or to comply with the study procedures or interfere with interpretation of study results.
- Other concurrent serious illness or medical conditions
- Absence of signed and dated participant informed consent form prior to enrollment into the study.
- History of hypersensitivity to docetaxel, polysorbate 80
- Known allergies, hypersensitivity or intolerance to prednisone or excipients of abiraterone acetate
- Known history of mineralocorticoid excess or deficiency
- Inadequate organ and bone marrow function
- Contraindications to the use of corticosteroid treatment.
- Symptomatic peripheral neuropathy grade > 1
- Concurrent treatment with strong inducers or strong inhibitors of cytochrome P450 (CYP450) 3A4
- Concurrent treatment with medications metabolized by cytochrome P2D6 (CYP2D6), particularly for those with a small therapeutic window
- History of cardiac arrhythmias requiring medical therapy such as atrial fibrillation requiring anticoagulation or digoxin/digitalis; uncontrolled angina pectoris. History of congestive heart failure or myocardial infarction within last 6 months was also not allowed.
- Uncontrolled hypertension (systolic BP ≥160 mmHg or diastolic BP ≥ 95 mmHg). Participants with a history of hypertension were allowed, provided that blood pressure was controlled to within these limits by anti-hypertensive treatment
- Clinically significant heart disease as evidenced by myocardial infarction, or arterial thrombotic events in the past 12 months, severe or unstable angina, or New York Heart Association Class III or IV heart disease or cardiac left ventricular ejection fraction measurement of <50% at baseline
- Participants with reproductive potential who did not agree to use accepted and effective method of contraception in conjunction with their partner(s) during the study treatment period.
- The above information is not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.
Trial locations and contacts
4 sites in 3 countries.
4 sites in 3 countries
United States2 sites
Investigational Site Number 840002
New Haven, Connecticut, 06510
Investigational Site Number 840001
San Francisco, California
United Kingdom1 site
Investigational Site Number 826001
Sutton, SM2 5PT
About this study
Official title: A Phase I/II Study of Cabazitaxel Combined With Abiraterone Acetate and Prednisone in Patients With Metastatic Castrate-Resistant Prostate Cancer (CRPC) Whose Disease Has Progressed After Docetaxel Chemotherapy
Primary Objectives:
- To determine the maximum tolerated dose, and dose limiting toxicities of cabazitaxel administered as a 1-hour infusion every 3 weeks in combination with oral daily abiraterone acetate and prednisone in participants with metastatic Castrate-resistant prostate cancer (CRPC)
- To estimate the anti-tumor activity of cabazitaxel in combination with abiraterone acetate and prednisone in terms of prostate-specific antigen (PSA) response rate.
Read more
Secondary Objectives:
- To characterize the safety profile of the combination
- To evaluate the pharmacokinetic profile of cabazitaxel and abiraterone in the proposed combination and dosing schedule
- To assess preliminary antitumor activity of the combination in terms of progression-free survival, PSA progression free survival and objective response rate, and overall survival
Read the detailed description
The study duration was to include a period for inclusion of up to 3 weeks and a 3-week treatment cycle(s). The participants might continue treatment until disease progression, unacceptable toxicity or willingness to stop followed by a minimum of 30-day follow-up
- Conditions
- Prostate Cancer
- Being tested
- Cabazitaxel XRP6258, Abiraterone acetate, Prednisone 5 mg
- Medical subject headings
- Prostatic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Cabazitaxel XRP6258Drug
Pharmaceutical form:solution Route of administration: injection
Abiraterone acetateDrug
Pharmaceutical form:tablets Route of administration: oral
Prednisone 5 mgDrug
Route of administration: oral
| Study group | Role | What they receive |
|---|---|---|
| Phase 1: Cabazitaxel 20 mg/m^2 + Abiraterone 1000 mg | Experimental | Cabazitaxel 20 mg/m^2 intravenous (IV) infusion on Day 1 of each 21-day cycle in combination with abiraterone acetate 1000 mg orally once daily and prednisone 5 mg orally twice daily until disease progression, unacceptable toxicity or consent withdrawal. Receives: Drug: Cabazitaxel XRP6258; Drug: Abiraterone acetate; Drug: Prednisone 5 mg |
| Phase 1: Cabazitaxel 25 mg/m^2 + Abiraterone 1000 mg | Experimental | Cabazitaxel 25 mg/m^2 IV infusion on Day 1 of each 21-day cycle in combination with abiraterone acetate 1000 mg orally once daily and prednisone 5 mg orally twice daily until disease progression, unacceptable toxicity or consent withdrawal. Receives: Drug: Cabazitaxel XRP6258; Drug: Abiraterone acetate; Drug: Prednisone 5 mg |
| Phase 2: Cabazitaxel 25 mg/m^2 + Abiraterone 1000 mg | Experimental | Cabazitaxel at maximum tolerated dose (MTD) as determined in phase 1 part (25 mg/m^2) IV infusion on Day 1 of each 21-day cycle in combination with abiraterone acetate 1000 mg orally once daily and prednisone 5 mg orally twice daily until disease progression, unacceptable toxicity or consent withdrawal. Receives: Drug: Cabazitaxel XRP6258; Drug: Abiraterone acetate; Drug: Prednisone 5 mg |
What is being measured
The primary outcome is the main question the study is designed to answer.
Phase 1: Maximally Tolerated Dose (MTD) of Cabazitaxel in Combination With Abiraterone Acetate
MTD was defined as highest dose level of cabazitaxel in combination with abiraterone acetate at which no more than 1 participant experienced dose limiting toxicities (DLT). DLT was defined as any of the following events related to study treatment: 1) Grade 3 or 4 non-hematological related adverse event with exception of Grade 3 fever without documented infection; Grade 3 nausea, vomiting, or diarrhea in the absence of effective maximal therapy; and Grade 3 hypersensitivity reaction in the absence of required premedication. 2) Hematological toxicity: Febrile neutropenia (fever of unknown origin ≥38.5°C with neutropenia Grade 3 or 4); Neutropenia Grade 4 lasting >7 days; Thrombocytopenia Grade 4 or Grade 3 complicated by hemorrhage. 3) Re-treatment delay of more than 2 weeks due to delayed recovery from a toxicity related to study treatment to baseline or ≤ Grade 1 (except for alopecia). Grades were based on National Cancer Institute CommonTerminology Criteria for Adverse Events v4.03.
Measured: Up to Cycle 2 of Phase 1 (up to 42 days)
Phase 2: Percentage of Participants With Prostate Specific Antigen (PSA) Response
Prostate specific antigen (PSA) response was defined as ≥50% decrease from baseline in serum PSA levels, confirmed at least 3 weeks later. Increases of any magnitude during the first 12 weeks were ignored in determining PSA response. PSA was to be measured at baseline, every 3 weeks, throughout study period, until progression. PSA progression was defined as: -An increase of 25% above the nadir (at least 2 ng/mL), confirmed by a second PSA value at least 3 weeks apart, in participants who have achieved a ≥50% decline of PSA. -An increase in PSA by 25 % above the baseline level (at least 2 ng/mL), confirmed by a second PSA value at least 3 weeks apart, in participants who have not achieved a ≥50% decline of PSA.
Measured: Baseline, every 3 weeks up to PSA progression (maximum duration: 603 days)
Secondary outcomes (13)
Phase 2: Objective Progression Free Survival (PFS)
Objective PFS was defined as the time interval between the date of enrollment and the first occurrence of any of the events:
- Radiological tumor progression (assessed using Response Evaluation Criteria in Solid Tumors [RECIST] version 1.1) was defined as at least a 20 percent increase in the sum of the longest diameter (LD) of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions and/or unequivocal progression of existing non target-lesions. in case of progressive disease (PD) diagnosed only on non target bone lesions on bone scan, PD was to be considered only in case of appearance of at least 2 new lesions on bone scan confirmed 6 weeks later by another bone scan, and at least the appearance of 2 new additional lesions. 2) Death due to any cause.
Analysis was performed by Kaplan-Meier method.
Measured: From baseline until radiological tumor or disease progression or death due to any cause, assessed up to Month 5
Phase 2: PSA Progression Free Survival
Prostate-specific antigen progression-free survival was defined as the time interval between the date of treatment start and the date of either first documented PSA progression or death due to any cause, whichever was earlier. PSA was to be measured at baseline, every 3 weeks, throughout study period, until progression. PSA progression was defined as: -An increase of 25% above the nadir (at least 2 ng/mL), confirmed by a second PSA value at least 3 weeks apart, in participants who have achieved a ≥50% decline of PSA. -An increase in PSA by 25 % above the baseline level (at least 2 ng/mL), confirmed by a second PSA value at least 3 weeks apart, in participants who have not achieved a ≥50% decline of PSA.
Analysis was performed by Kaplan Meire method.
Measured: Baseline, every 3 weeks up to PSA progression (maximum duration: 603 days)
Phase 2: Percentage of Participants With Objective Response
Objective response was defined as having complete response (CR) or Partial Response (PR) assessed by RECIST 1.1. CR was defined as disappearance of all target, non-target lesions; normalization of tumor marker level and all lymph nodes size was <10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions (taking as reference the baseline sum diameters).
Measured: Baseline, every 12 weeks there after until disease progression (maximum duration: 603 days)
Phase 2: Overall Survival
Overall survival was defined as the time interval from the date of treatment start to the date of death due to any cause. In absence of confirmation of death, survival time was censored at the earlier of the last date the participant was known to be alive and the study cut-off date. Analysis was performed by Kaplan-Meier method.
Measured: From baseline up to death or study cut-off (maximum duration: 603 days)
Phase 2: Pharmacokinetic of Cabazitaxel : Maximum Plasma Concentration Observed (Cmax)
Measured: 5 minutes before cabazitaxel infusion; at end of cabazitaxel infusion; 0.25 hours post-cabazitaxel infusion; any time between 1 to 4 hours, between 6 to 24 hours, between 48 to 96 hours post cabazitaxel infusion on Day 1-Cycle 1
Phase 2: Pharmacokinetic of Cabazitaxel : Area Under the Plasma Concentration Versus Time Curve (AUC)
Area under the concentration-time curve calculated using the following equation: AUC = Plasma clearance (CL)/dose
Measured: 5 minutes before cabazitaxel infusion; at end of cabazitaxel infusion; 0.25 hours post-cabazitaxel infusion; any time between 1 to 4 hours, between 6 to 24 hours, between 48 to 96 hours post cabazitaxel infusion on Day 1-Cycle 1
Phase 2: Pharmacokinetic of Cabazitaxel : Terminal Half-life (t 1/2z)
Measured: 5 minutes before cabazitaxel infusion; at end of cabazitaxel infusion; 0.25 hours post-cabazitaxel infusion; any time between 1 to 4 hours, between 6 to 24 hours, between 48 to 96 hours post cabazitaxel infusion on Day 1-Cycle 1
Phase 2: Pharmacokinetic of Cabazitaxel : Total Plasma Clearance (CL)
Measured: 5 minutes before cabazitaxel infusion; at end of cabazitaxel infusion; 0.25 hours post-cabazitaxel infusion; any time between 1 to 4 hours, between 6 to 24 hours, between 48 to 96 hours post cabazitaxel infusion on Day 1-Cycle 1
Phase 2: Pharmacokinetic of Cabazitaxel : Volume of Distribution at Steady State (Vss)
Measured: 5 minutes before cabazitaxel infusion; at end of cabazitaxel infusion; 0.25 hours post-cabazitaxel infusion; any time between 1 to 4 hours, between 6 to 24 hours, between 48 to 96 hours post cabazitaxel infusion on Day 1-Cycle 1
Phase 2: Pharmacokinetic of Abiraterone : Maximum Plasma Concentration Observed (Cmax)
Measured: 0 hour (before abiraterone administration); 1, 2, 4, 6, 8, 12, 24 hours post abiraterone administration on Day 1-Cycle 1
Phase 2: Pharmacokinetic of Abiraterone : First Time to Reach Cmax (Tmax)
Measured: 0 hour (before abiraterone administration); 1, 2, 4, 6, 8, 12, 24 hours post abiraterone administration on Day 1-Cycle 1
Phase 2: Pharmacokinetic of Abiraterone : Area Under the Plasma Concentration Versus Time Curve From Time 0 to 24 Hours (AUC 0-24)
Area under the plasma concentration-time curve calculated using the trapezoidal method from time zero to 24 hours corresponding to abiraterone acetate dosing interval.
Measured: 0 hour (before abiraterone administration); 1, 2, 4, 6, 8, 12, 24 hours post abiraterone administration on Day 1-Cycle 1
Phase 2: Pharmacokinetic of Abiraterone : Concentration Observed Just Before Treatment Administration During Repeated Dosing at Steady State (Ctrough ss)
Measured: Pre abiraterone dose on Day 1 of Cycle 1
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Jan 2012 (estimated)
- Study startMar 2012
- Primary completionJul 2014
- Study completionDec 2014
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 (2)Papers the sponsor has linked to this study.
- Other trials for Prostate CancerStudies of the same condition, open and under way.
- More trials run by SanofiThe 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 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 38 participants (actual)
Sponsor and investigators
- Lead sponsor
- Sanofi
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Clinical Sciences & Operations, Study director, Sanofi
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01511536
- Sponsor's protocol ID
- TCD12128
- Other IDs
- 2011-001506-96, U1111-1121-6324
- Status last verified
- Jun 2016
- First submitted
- 4 Jan 2012
- Last updated
- 28 Jul 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Massard C, Mateo J, Loriot Y, Pezaro C, Albiges L, Mehra N, Varga A, Bianchini D, Ryan CJ, Petrylak DP, Attard G, Shen L, Fizazi K, de Bono J. Phase I/II trial of cabazitaxel plus abiraterone in patients with metastatic castration-resistant prostate cancer (mCRPC) progressing after docetaxel and abiraterone. Ann Oncol. 2017 Jan 1;28(1):90-95. doi: 10.1093/annonc/mdw441.
PubMed 28039155Huang X, Chau CH, Figg WD. Challenges to improved therapeutics for metastatic castrate resistant prostate cancer: from recent successes and failures. J Hematol Oncol. 2012 Jul 2;5:35. doi: 10.1186/1756-8722-5-35.
PubMed 22747660
Study at a glance
From the registry record, last updated by the sponsor on 28 Jul 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I/II Study of Cabazitaxel Combined With Abiraterone Acetate and Prednisone in Patients With Metastatic Castrate-Resistant Prostate Cancer (CRPC) Whose Disease Has Progressed After Docetaxel Chemotherapy
- ClinicalTrials.gov ID
- NCT01511536
- Acronym / sponsor ID
- TCD12128
- Conditions
- Prostate Cancer
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 38 participants (actual)
- Lead sponsor
- SanofiIndustry (pharma, biotech, devices)
- Study start
- Mar 2012
- Primary completion
- Jul 2014 (actual)
- Study completion
- Dec 2014 (actual)
- First posted
- 18 Jan 2012 (estimated)
- Results
- Posted 4 Nov 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Primary Objectives:
- To determine the maximum tolerated dose, and dose limiting toxicities of cabazitaxel administered as a 1-hour infusion every 3 weeks in combination with oral daily abiraterone acetate and prednisone in participants with metastatic Castrate-resistant prostate cancer (CRPC)
- To estimate the anti-tumor activity of cabazitaxel in combination with abiraterone acetate and prednisone in terms of prostate-specific antigen (PSA) response rate.
Secondary Objectives:
- To characterize the safety profile of the combination
- To evaluate the pharmacokinetic profile of cabazitaxel and abiraterone in the proposed combination and dosing schedule
- To assess preliminary antitumor activity of the combination in terms of progression-free survival, PSA progression free survival and objective response rate, and overall survival
Detailed description
The study duration was to include a period for inclusion of up to 3 weeks and a 3-week treatment cycle(s). The participants might continue treatment until disease progression, unacceptable toxicity or willingness to stop followed by a minimum of 30-day follow-up
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Phase 1: Cabazitaxel 20 mg/m^2 + Abiraterone 1000 mg | Experimental | Drug: Cabazitaxel XRP6258, Drug: Abiraterone acetate, Drug: Prednisone 5 mgCabazitaxel 20 mg/m^2 intravenous (IV) infusion on Day 1 of each 21-day cycle in combination with abiraterone acetate 1000 mg orally once daily and prednisone 5 mg orally twice daily until disease progression, unacceptable toxicity or consent withdrawal. |
| Phase 1: Cabazitaxel 25 mg/m^2 + Abiraterone 1000 mg | Experimental | Drug: Cabazitaxel XRP6258, Drug: Abiraterone acetate, Drug: Prednisone 5 mgCabazitaxel 25 mg/m^2 IV infusion on Day 1 of each 21-day cycle in combination with abiraterone acetate 1000 mg orally once daily and prednisone 5 mg orally twice daily until disease progression, unacceptable toxicity or consent withdrawal. |
| Phase 2: Cabazitaxel 25 mg/m^2 + Abiraterone 1000 mg | Experimental | Drug: Cabazitaxel XRP6258, Drug: Abiraterone acetate, Drug: Prednisone 5 mgCabazitaxel at maximum tolerated dose (MTD) as determined in phase 1 part (25 mg/m^2) IV infusion on Day 1 of each 21-day cycle in combination with abiraterone acetate 1000 mg orally once daily and prednisone 5 mg orally twice daily until disease progression, unacceptable toxicity or consent withdrawal. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Diagnosis of prostate adenocarcinoma proven histologically or cytologically, resistant to hormone therapy and previously treated with a docetaxel-containing regimen. In Phase 2 part, participants should have been treated with abiraterone acetate for at least 3 months and should continue treatment with abiraterone acetate before study entry
- Presence of metastatic prostate cancer.
- Participant must had progressive disease documented by rising PSA defined as 2 sequential increases above a previous lowest reference value (each PSA value must be obtained at least 1 week apart. A PSA value of at least 6 ng/mL was required at study entry). In Phase 1 part, in addition to rising PSA, progressive disease must be documented by:
- Effective castration (serum testosterone levels ≤0.50 ng/mL) by orchiectomy and/or luteinizing hormone-releasing hormone agonists /antagonist.
- Eastern Cooperative Oncology Group performance status: 0 - 1.
Key exclusion criteria (23 listed)
- Previous treatment with mitoxantrone or cabazitaxel.
- Prior bone-seeking radio-isotope therapy (participants treated with Radium223 were not excluded from the study). Radiotherapy to ≥30% of bone marrow.
- Adverse events from any prior anticancer therapy of grade >1 at the time of enrollment.
- Prior surgery, radiation, chemotherapy, or other anti-cancer therapy within 4 weeks prior to enrollment in the study (except luteinizing hormone-releasing hormone agonist /antagonist and abiraterone acetate in the Phase 2 part of the study); small field single fraction palliative radiation within 1 week.
- Prior malignancy. Curatively treated basal cell or squamous cell skin or superficial (pTis, pTa, and pT1) bladder cancer were allowed, as well as any other cancer for which chemotherapy had been completed ≥ 3 years ago and from which the participant had been disease-free for ≥ 3 years.
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 |
|---|---|---|
| Cabazitaxel XRP6258Pharmaceutical form:solution Route of administration: injection | Drug | Phase 1: Cabazitaxel 20 mg/m^2 + Abiraterone 1000 mg, Phase 1: Cabazitaxel 25 mg/m^2 + Abiraterone 1000 mg, Phase 2: Cabazitaxel 25 mg/m^2 + Abiraterone 1000 mg |
| Abiraterone acetatePharmaceutical form:tablets Route of administration: oral | Drug | Phase 1: Cabazitaxel 20 mg/m^2 + Abiraterone 1000 mg, Phase 1: Cabazitaxel 25 mg/m^2 + Abiraterone 1000 mg, Phase 2: Cabazitaxel 25 mg/m^2 + Abiraterone 1000 mg |
| Prednisone 5 mgRoute of administration: oral | Drug | Phase 1: Cabazitaxel 20 mg/m^2 + Abiraterone 1000 mg, Phase 1: Cabazitaxel 25 mg/m^2 + Abiraterone 1000 mg, Phase 2: Cabazitaxel 25 mg/m^2 + Abiraterone 1000 mg |
Primary outcome
Phase 1: Maximally Tolerated Dose (MTD) of Cabazitaxel in Combination With Abiraterone Acetate
Time frame: Up to Cycle 2 of Phase 1 (up to 42 days)
MTD was defined as highest dose level of cabazitaxel in combination with abiraterone acetate at which no more than 1 participant experienced dose limiting toxicities (DLT). DLT was defined as any of the following events related to study treatment: 1) Grade 3 or 4 non-hematological related adverse event with exception of Grade 3 fever without documented infection; Grade 3 nausea, vomiting, or diarrhea in the absence of effective maximal therapy; and Grade 3 hypersensitivity reaction in the absence of required premedication. 2) Hematological toxicity: Febrile neutropenia (fever of unknown origin ≥38.5°C with neutropenia Grade 3 or 4); Neutropenia Grade 4 lasting >7 days; Thrombocytopenia Grade 4 or Grade 3 complicated by hemorrhage. 3) Re-treatment delay of more than 2 weeks due to delayed recovery from a toxicity related to study treatment to baseline or ≤ Grade 1 (except for alopecia). Grades were based on National Cancer Institute CommonTerminology Criteria for Adverse Events v4.03.
Phase 2: Percentage of Participants With Prostate Specific Antigen (PSA) Response
Time frame: Baseline, every 3 weeks up to PSA progression (maximum duration: 603 days)
Prostate specific antigen (PSA) response was defined as ≥50% decrease from baseline in serum PSA levels, confirmed at least 3 weeks later. Increases of any magnitude during the first 12 weeks were ignored in determining PSA response. PSA was to be measured at baseline, every 3 weeks, throughout study period, until progression. PSA progression was defined as: -An increase of 25% above the nadir (at least 2 ng/mL), confirmed by a second PSA value at least 3 weeks apart, in participants who have achieved a ≥50% decline of PSA. -An increase in PSA by 25 % above the baseline level (at least 2 ng/mL), confirmed by a second PSA value at least 3 weeks apart, in participants who have not achieved a ≥50% decline of PSA.
13 secondary outcomes
Phase 2: Objective Progression Free Survival (PFS)
Time frame: From baseline until radiological tumor or disease progression or death due to any cause, assessed up to Month 5
Phase 2: PSA Progression Free Survival
Time frame: Baseline, every 3 weeks up to PSA progression (maximum duration: 603 days)
Phase 2: Percentage of Participants With Objective Response
Time frame: Baseline, every 12 weeks there after until disease progression (maximum duration: 603 days)
Phase 2: Overall Survival
Time frame: From baseline up to death or study cut-off (maximum duration: 603 days)
Phase 2: Pharmacokinetic of Cabazitaxel : Maximum Plasma Concentration Observed (Cmax)
Time frame: 5 minutes before cabazitaxel infusion; at end of cabazitaxel infusion; 0.25 hours post-cabazitaxel infusion; any time between 1 to 4 hours, between 6 to 24 hours, between 48 to 96 hours post cabazitaxel infusion on Day 1-Cycle 1
Phase 2: Pharmacokinetic of Cabazitaxel : Area Under the Plasma Concentration Versus Time Curve (AUC)
Time frame: 5 minutes before cabazitaxel infusion; at end of cabazitaxel infusion; 0.25 hours post-cabazitaxel infusion; any time between 1 to 4 hours, between 6 to 24 hours, between 48 to 96 hours post cabazitaxel infusion on Day 1-Cycle 1
Phase 2: Pharmacokinetic of Cabazitaxel : Terminal Half-life (t 1/2z)
Time frame: 5 minutes before cabazitaxel infusion; at end of cabazitaxel infusion; 0.25 hours post-cabazitaxel infusion; any time between 1 to 4 hours, between 6 to 24 hours, between 48 to 96 hours post cabazitaxel infusion on Day 1-Cycle 1
Phase 2: Pharmacokinetic of Cabazitaxel : Total Plasma Clearance (CL)
Time frame: 5 minutes before cabazitaxel infusion; at end of cabazitaxel infusion; 0.25 hours post-cabazitaxel infusion; any time between 1 to 4 hours, between 6 to 24 hours, between 48 to 96 hours post cabazitaxel infusion on Day 1-Cycle 1
Phase 2: Pharmacokinetic of Cabazitaxel : Volume of Distribution at Steady State (Vss)
Time frame: 5 minutes before cabazitaxel infusion; at end of cabazitaxel infusion; 0.25 hours post-cabazitaxel infusion; any time between 1 to 4 hours, between 6 to 24 hours, between 48 to 96 hours post cabazitaxel infusion on Day 1-Cycle 1
Phase 2: Pharmacokinetic of Abiraterone : Maximum Plasma Concentration Observed (Cmax)
Time frame: 0 hour (before abiraterone administration); 1, 2, 4, 6, 8, 12, 24 hours post abiraterone administration on Day 1-Cycle 1
Phase 2: Pharmacokinetic of Abiraterone : First Time to Reach Cmax (Tmax)
Time frame: 0 hour (before abiraterone administration); 1, 2, 4, 6, 8, 12, 24 hours post abiraterone administration on Day 1-Cycle 1
Phase 2: Pharmacokinetic of Abiraterone : Area Under the Plasma Concentration Versus Time Curve From Time 0 to 24 Hours (AUC 0-24)
Time frame: 0 hour (before abiraterone administration); 1, 2, 4, 6, 8, 12, 24 hours post abiraterone administration on Day 1-Cycle 1
Phase 2: Pharmacokinetic of Abiraterone : Concentration Observed Just Before Treatment Administration During Repeated Dosing at Steady State (Ctrough ss)
Time frame: Pre abiraterone dose on Day 1 of Cycle 1
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Jul 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 28039155Massard C, Mateo J, Loriot Y, Pezaro C, Albiges L, Mehra N, Varga A, Bianchini D, Ryan CJ, Petrylak DP, Attard G, Shen L, Fizazi K, de Bono J. Phase I/II trial of cabazitaxel plus abiraterone in patients with metastatic castration-resistant prostate cancer (mCRPC) progressing after docetaxel and abiraterone. Ann Oncol. 2017 Jan 1;28(1):90-95. doi: 10.1093/annonc/mdw441.
- Derived from this study: PubMed 22747660Huang X, Chau CH, Figg WD. Challenges to improved therapeutics for metastatic castrate resistant prostate cancer: from recent successes and failures. J Hematol Oncol. 2012 Jul 2;5:35. doi: 10.1186/1756-8722-5-35.
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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.
Clinical Sciences & Operations study director
Sanofi
4 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 Cabazitaxel XRP6258, Abiraterone acetate and Prednisone 5 mg in people with Prostate Cancer, run by Sanofi at 4 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 9 inclusion and 23 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 28 Jul 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in United States, France, 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 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 4 Nov 2015). 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?
Phase 1: Maximally Tolerated Dose (MTD) of Cabazitaxel in Combination With Abiraterone Acetate (time frame: Up to Cycle 2 of Phase 1 (up to 42 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 NCT01511536, which also lists 2 linked publications.
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 28 Jul 2016.