Cabazitaxel and Abiraterone Acetate in Patients With Metastatic Castrate-Resistant Prostate Cancer

NCT01511536 | Completed Phase 1 Results

• 3 other identifiers: TCD121282011-001506-96U1111-1121-6324
• Study Type: interventional
• Target: 38
• Locations: 3 countries
• Sites: 4

Brief 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 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

Conditions

Prostate Cancer

Outcome Measures

Primary Outcomes (2)

• 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 (13)

• Phase 2: Objective Progression Free Survival (PFS)

  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

  Baseline, every 3 weeks up to PSA progression (maximum duration: 603 days)

• Phase 2: Percentage of Participants With Objective Response

  Baseline, every 12 weeks there after until disease progression (maximum duration: 603 days)

• Phase 2: Overall Survival

  From baseline up to death or study cut-off (maximum duration: 603 days)

• Phase 2: Pharmacokinetic of Cabazitaxel : Maximum Plasma Concentration Observed (Cmax)

  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

Study Arms (3)

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

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; Phase 2: Cabazitaxel 25 mg/m^2 + Abiraterone 1000 mg

Abiraterone acetate DRUG

Pharmaceutical form:tablets Route of administration: oral

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 mg DRUG

Route of administration: oral

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

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Sanofi: lead

Study Sites (4)

Investigational Site Number 840001

San Francisco, California, United States

Location

Investigational Site Number 840002

New Haven, Connecticut, 06510, United States

Location

Investigational Site Number 250001

Villejuif, 94805, France

Location

Investigational Site Number 826001

Sutton, SM2 5PT, United Kingdom

Location

Related Publications (2)

• 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.

  PMID: 28039155 DERIVED

• Huang 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.

  PMID: 22747660 DERIVED

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

Abiraterone Acetate; Prednisone

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Androstenes; Androstanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Pregnadienediols; Pregnadienes; Pregnanes

Results Point of Contact

• Title: Trial Transparency Team
• Organization: Sanofi

Contact-US@sanofi.com

Study Officials

• Clinical Sciences & Operations

  Sanofi

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 4, 2012
• First Posted: January 18, 2012
• Study Start: March 1, 2012
• Primary Completion: July 1, 2014
• Study Completion: December 1, 2014
• Last Updated: July 28, 2016
• Results First Posted: November 4, 2015

Record last verified: 2016-06

Locations

US (2); GB (1); FR (1)