Cabazitaxel and Abiraterone Acetate in Patients With Meta... | NCT01511536

NCT01511536

Protocol Section

Identification Module

Results Section

Participant Flow Module

Annotation Section

No data available

No data is available for this block.

Document Section

No data available

No data is available for this block.

Derived Section

Miscellaneous Info Module

ID	Type	Description	Link
2011-001506-96	EudraCT Number
U1111-1121-6324	Other Identifier	UTN

Status Module

Description Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
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.	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.	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.	Drug: Cabazitaxel XRP6258 Drug: Abiraterone acetate Drug: Prednisone 5 mg

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Cabazitaxel XRP6258	Drug	Pharmaceutical form:solution Route of administration: injection	Phase 1: Cabazitaxel 20 mg/m^2 + Abiraterone 1000 mg Phase 1: Cabazitaxel 25 mg/m^2 + Abiraterone 1000 mg

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
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.	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.	Baseline, every 3 weeks up to PSA progression (maximum duration: 603 days)

Secondary Outcomes

Measure	Description	Time Frame
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.

Eligibility Module

Eligibility Criteria

Inclusion criteria :

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:
1. Increase in non-measureable or measurable disease, and/or
2. 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.
1. 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.
2. Prior anti-androgen therapy should be stopped before enrollment
Eastern Cooperative Oncology Group performance status: 0 - 1.

Exclusion criteria:

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.
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.

Name	Affiliation	Role
Clinical Sciences & Operations	Sanofi	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Investigational Site Number 840001		San Francisco	California		United States
Investigational Site Number 840002

PubMed Identifier	Type	Citation	Retractions
28039155	Derived	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.
22747660

Arm/Group Information

ID	Title	Description
FG000	Phase 1: Cabazitaxel 20 mg/m^2 + Abiraterone 1000 mg	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.
FG001	Phase 1: Cabazitaxel 25 mg/m^2 + Abiraterone 1000 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.
FG002	Phase 2: Cabazitaxel 25 mg/m^2 + Abiraterone 1000 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.

ID	Title	Description
BG000	Phase 1: Cabazitaxel 20 mg/m^2 + Abiraterone 1000 mg	Cabazitaxel 20 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.
BG001

Units	Counts
Participants	BG000

Title	Description	Population Description	Parameter Type	Dispersion Type	Unit of Measure	Calculate Percentage	Denominator Units Selected	Denominators	Classes
Age, Continuous			Mean

Outcome Measures Module

Outcome Measures

Type	Title	Description	Population Description	Reporting Status	Anticipated Posting Date	Parameter Type	Dispersion Type	Unit of Measure	Calculate Percentage	Time Frame	Units Analyzed	Denominator Units Selected	Arm/Group Information	Denominators	Classes	Analyses
Primary	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.	Analysis was performed on DLT evaluable population defined as all participants who received the first 2 cycles, unless they discontinued the study drug during the first 2 cycles for a DLT.	Posted		Number		mg/m^2		Up to Cycle 2 of Phase 1 (up to 42 days)

Adverse Events Module

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Phase 1: Cabazitaxel 20 mg/m^2 + Abiraterone 1000 mg	Cabazitaxel 20 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.

ID	Term
D005834	Genital Neoplasms, Male
D014565	Urogenital Neoplasms
D009371	Neoplasms by Site
D009369	Neoplasms

ID	Term
D000736	Androstenes
D000731	Androstanes
D013256	Steroids
D000072473	Fused-Ring Compounds