A Phase 1/2 interventional study of Cabazitaxel XRP6258 and Abiraterone acetate in Prostate Cancer, sponsored by Sanofi. Completed at 4 sites in 3 countries. Open to male participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2016-07-28.
Sponsored by Sanofi · Phase 1/2, Interventional, and Treatment
Primary Objectives:
Secondary Objectives:
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
6,370 studies on the registry are indexed under Prostatic Neoplasms; 1,400 are open to participants now.
This study's enrollment of 38 is below the median of 58 across 4,822 interventional studies indexed under Prostatic Neoplasms.
Browse Prostatic Neoplasms studies →Sanofi is the lead sponsor of 1,508 studies on the registry; 90 are open to participants now.
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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.
Exclusion criteria:
Previous treatment with mitoxantrone or cabazitaxel.
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.
The above information is not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.
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.
Drug: Cabazitaxel XRP6258 · Drug: Abiraterone acetate · Drug: Prednisone 5 mg
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.
Drug: Cabazitaxel XRP6258 · Drug: Abiraterone acetate · Drug: Prednisone 5 mg
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.
Drug: Cabazitaxel XRP6258 · Drug: Abiraterone acetate · Drug: Prednisone 5 mg
Pharmaceutical form:solution Route of administration: injection
Pharmaceutical form:tablets Route of administration: oral
Route of administration: oral
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.
Time frame: 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.
Time frame: Baseline, every 3 weeks up to PSA progression (maximum duration: 603 days)
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: 1) 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.
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
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.
Time frame: 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).
Time frame: 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.
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)
Area under the concentration-time curve calculated using the following equation: AUC = Plasma clearance (CL)/dose
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)
Area under the plasma concentration-time curve calculated using the trapezoidal method from time zero to 24 hours corresponding to abiraterone acetate dosing interval.
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
Participants were enrolled at 2 centers in phase 1 part and 3 centers in phase 2 part between March 2012 and April 2014.
| Milestone | 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 |
|---|---|---|---|
| Started | 3 | 7 | 0 |
| Completed | 3 | 6 | 0 |
| Not completed | 0 | 1 | 0 |
| Withdrew: Other | 0 | 1 | 0 |
| Milestone | 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 |
|---|---|---|---|
| Started | 0 | 0 | 27 |
| Completed | 0 | 0 | 18 |
| Not completed | 0 | 0 | 9 |
| Withdrew: Other | 0 | 0 | 9 |
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.
| mg/m^2 | Phase 1: Overall Population |
|---|---|
| Phase 1: Maximally Tolerated Dose (MTD) of Cabazitaxel in Combination With Abiraterone Acetate | 25 |
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.
| percentage of participants | Phase 2: Cabazitaxel 25 mg/m^2 + Abiraterone 1000 mg |
|---|---|
| Phase 2: Percentage of Participants With Prostate Specific Antigen (PSA) Response | 46.2 (26.6 to 66.6) |
Objective PFS was defined as the time interval between the date of enrollment and the first occurrence of any of the events: 1) 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.
| months | Phase 2: Cabazitaxel 25 mg/m^2 + Abiraterone 1000 mg |
|---|---|
| Phase 2: Objective Progression Free Survival (PFS) | NA (4.731 to NA) |
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.
| months | Phase 2: Cabazitaxel 25 mg/m^2 + Abiraterone 1000 mg |
|---|---|
| Phase 2: PSA Progression Free Survival | 6.93 (4.140 to 10.251) |
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).
| percentage of participants | Phase 2: Cabazitaxel 25 mg/m^2 + Abiraterone 1000 mg |
|---|---|
| Phase 2: Percentage of Participants With Objective Response | 21.4 (4.7 to 50.8) |
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.
| months | Phase 2: Cabazitaxel 25 mg/m^2 + Abiraterone 1000 mg |
|---|---|
| Phase 2: Overall Survival | NA (9.429 to NA) |
| ng/mL | Phase 2: Cabazitaxel 25 mg/m^2 + Abiraterone 1000 mg |
|---|---|
| Phase 2: Pharmacokinetic of Cabazitaxel : Maximum Plasma Concentration Observed (Cmax) | 330 ± 187 |
Area under the concentration-time curve calculated using the following equation: AUC = Plasma clearance (CL)/dose
| ng*h/mL | Phase 2: Cabazitaxel 25 mg/ m^2 + Abiraterone 1000 mg |
|---|---|
| Phase 2: Pharmacokinetic of Cabazitaxel : Area Under the Plasma Concentration Versus Time Curve (AUC) | 817 ± 117 |
| hour | Phase 2: Cabazitaxel 25 mg/ m^2 + Abiraterone 1000 mg |
|---|---|
| Phase 2: Pharmacokinetic of Cabazitaxel : Terminal Half-life (t 1/2z) | 91.6 ± 62.6 |
| L/h/m^2 | Phase 2: Cabazitaxel 25 mg/ m^2 + Abiraterone 1000 mg |
|---|---|
| Phase 2: Pharmacokinetic of Cabazitaxel : Total Plasma Clearance (CL) | 31.4 ± 4.67 |
| L/m^2 | Phase 2: Cabazitaxel 25 mg/ m^2 + Abiraterone 1000 mg |
|---|---|
| Phase 2: Pharmacokinetic of Cabazitaxel : Volume of Distribution at Steady State (Vss) | 2711 ± 2493 |
| ng/mL | Phase 2: Cabazitaxel 25 mg/ m^2 + Abiraterone 1000 mg |
|---|---|
| Phase 2: Pharmacokinetic of Abiraterone : Maximum Plasma Concentration Observed (Cmax) | 216 ± 152 |
| hour | Phase 2: Cabazitaxel 25 mg/ m^2 + Abiraterone 1000 mg |
|---|---|
| Phase 2: Pharmacokinetic of Abiraterone : First Time to Reach Cmax (Tmax) | 2.00 (1.00 to 6.00) |
Area under the plasma concentration-time curve calculated using the trapezoidal method from time zero to 24 hours corresponding to abiraterone acetate dosing interval.
| ng*h/mL | Phase 2: Cabazitaxel 25 mg/ m^2 + Abiraterone 1000 mg |
|---|---|
| Phase 2: Pharmacokinetic of Abiraterone : Area Under the Plasma Concentration Versus Time Curve From Time 0 to 24 Hours (AUC 0-24) | 928 ± 466 |
| ng/mL | Phase 2: Cabazitaxel 25 mg/ m^2 + Abiraterone 1000 mg |
|---|---|
| Phase 2: Pharmacokinetic of Abiraterone : Concentration Observed Just Before Treatment Administration During Repeated Dosing at Steady State (Ctrough ss) | 9.99 ± 13.0 |
Collected over All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (603 days) regardless of seriousness or relationship to investigational product. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Phase 1: Cabazitaxel 20 mg/m^2 + Abiraterone 1000 mg | — | 3/3 (100%) | 3/3 (100%) |
| Phase 1: Cabazitaxel 25 mg/m^2 + Abiraterone 1000 mg | — | 4/7 (57.1%) | 7/7 (100%) |
| Phase 2: Cabazitaxel 25 mg/m^2 + Abiraterone 1000 mg | — | 21/27 (77.8%) | 27/27 (100%) |
| Event | 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 |
|---|---|---|---|
| Small cell lung cancerNeoplasms benign, malignant and unspecified (incl cysts and polyps) | 1/3 | 0/7 | 0/27 |
| Cardiac failureCardiac disorders | 1/3 | 0/7 | 0/27 |
| Myocardial ischaemiaCardiac disorders | 1/3 | 0/7 | 0/27 |
| ProstatitisReproductive system and breast disorders | 1/3 | 0/7 | 0/27 |
| FatigueGeneral disorders | 1/3 | 1/7 | 0/27 |
| Urinary tract infectionInfections and infestations | 0/3 | 0/7 | 4/27 |
| HydronephrosisRenal and urinary disorders | 0/3 | 0/7 | 4/27 |
| Parasitic gastroenteritisInfections and infestations | 0/3 | 1/7 | 0/27 |
| DyspnoeaRespiratory, thoracic and mediastinal disorders | 0/3 | 1/7 | 1/27 |
| Abdominal painGastrointestinal disorders | 0/3 | 1/7 | 0/27 |
| Event | 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 |
|---|---|---|---|
| NauseaGastrointestinal disorders | 1/3 | 5/7 | 14/27 |
| InsomniaPsychiatric disorders | 2/3 | 0/7 | 0/27 |
| Abdominal pain upperGastrointestinal disorders | 2/3 | 1/7 | 0/27 |
| ConstipationGastrointestinal disorders | 2/3 | 2/7 | 6/27 |
| DiarrhoeaGastrointestinal disorders | 2/3 | 3/7 | 15/27 |
| AstheniaGeneral disorders | 2/3 | 3/7 | 16/27 |
| PyrexiaGeneral disorders | 2/3 | 0/7 | 3/27 |
| Decreased appetiteMetabolism and nutrition disorders | 1/3 | 1/7 | 13/27 |
| Weight decreasedInvestigations | 0/3 | 2/7 | 13/27 |
| DyspnoeaRespiratory, thoracic and mediastinal disorders | 0/3 | 2/7 | 11/27 |
All treated/safety population defined as all registered participants exposed to both investigational medicinal product (IMP) components, regardless of the amount of treatment administered.
| Age, Continuous(years) | 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 | Total |
|---|---|---|---|---|
| Mean | 71.0 ± 7.0 | 60.0 ± 10.0 | 67.1 ± 5.4 | 66.1 ± 7.1 |
| Sex: Female, Male(Participants) | 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 | Total |
|---|---|---|---|---|
| Female | 0 | 0 | 0 | 0 |
| Male | 3 | 7 | 27 | 37 |
This study is completed, as verified in Jun 2016. You cannot join it, but the record below documents what was studied.
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