Cabazitaxel and Abiraterone Acetate in Patients With Metastatic Castrate-Resistant Prostate Cancer
This study is currently recruiting participants.
Verified November 2013 by Sanofi
Information provided by (Responsible Party):
First received: January 4, 2012
Last updated: November 7, 2013
Last verified: November 2013
- 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 patients with metastatic CRPC
- To estimate the anti-tumor activity of cabazitaxel in combination with abiraterone acetate and prednisone in terms of PSA response rate.
- 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
Drug: Cabazitaxel XRP6258
Drug: Abiraterone acetate
||Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
||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 Outcome Measures:
- Maximally tolerated dose of cabazitaxel in combination with abiraterone acetate [ Time Frame: up to 8 months ] [ Designated as safety issue: No ]
- PSA Response Rate [ Time Frame: up to 3 years ] [ Designated as safety issue: No ]
Secondary Outcome Measures:
- Overall safety profile of the combination in terms of Treatment-emergent adverse events and laboratory abnormalities [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
- Objective PFS [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
- PSA progression free survival [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
- Objective response rate [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
- Overall survival [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
- Cabazitaxel : Maximum plasma concentration observed [ Time Frame: Up to 1 month ] [ Designated as safety issue: No ]
- Cabazitaxel : Area under the plasma concentration versus time curve [ Time Frame: Up to 1 month ] [ Designated as safety issue: No ]
- Cabazitaxel : extrapolated to infinity [ Time Frame: Up to 1 month ] [ Designated as safety issue: No ]
- Cabazitaxel : Terminal half-life associated with the terminal slope (λz) [ Time Frame: Up to 1 month ] [ Designated as safety issue: No ]
- Cabazitaxel : Apparent Total Body Clearance from the plasma [ Time Frame: Up to 1 month ] [ Designated as safety issue: No ]
- Cabazitaxel : Volume of distribution at steady state [ Time Frame: Up to 1 month ] [ Designated as safety issue: No ]
- Abiraterone : Maximum plasma concentration observed [ Time Frame: Up to 1 month ] [ Designated as safety issue: No ]
- Abiraterone : First time to reach Cmax [ Time Frame: Up to 1 month ] [ Designated as safety issue: No ]
- Abiraterone : Area under the plasma concentration versus time curve calculated using the trapezoidal method from 0 to 24 hours post dosing [ Time Frame: Up to 1 month ] [ Designated as safety issue: No ]
- Abiraterone : Concentration observed just before treatment administration during repeated dosing at steady state [ Time Frame: Up to 1 month ] [ Designated as safety issue: No ]
| Estimated Enrollment:
| Study Start Date:
| Estimated Study Completion Date:
| Estimated Primary Completion Date:
||January 2014 (Final data collection date for primary outcome measure)
Experimental: Dose escalation and expansion
Cabaxitaxel administered once every 3 weeks + abiraterone acetate 1000 mg/day + prednisone 10 mg/day
Drug: Cabazitaxel XRP6258
Pharmaceutical form:solution Route of administration: injection
Drug: Abiraterone acetate
Pharmaceutical form:tablets Route of administration: oral
The study duration will include a period for inclusion of up to 3 weeks and a 3-week treatment cycle(s). The patients may continue treatment until disease progression, unacceptable toxicity or willingness to stop followed by a minimum of 30-day follow-up
|Ages Eligible for Study:
||18 Years and older
|Genders Eligible for Study:
|Accepts Healthy Volunteers:
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, patients 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.
Patient must have 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 is 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 patient has been treated with luteinizing hormone-releasing hormone agonists/antagonist (i.e., without orchiectomy), then this therapy must have 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.
Previous treatment with mitoxantrone or cabazitaxel.
- Prior bone-seeking radio-isotope therapy (patients treated with Radium223 are 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 hormoneagonist /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 are allowed, as well as any other cancer for which chemotherapy has been completed ≥ 3 years ago and from which the patient has 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 patient 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 patient 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 CYP450 3A4
- Concurrent treatment with medications metabolized by 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 is also not allowed.
- Uncontrolled hypertension (systolic BP ≥160 mmHg or diastolic BP ≥ 95 mmHg). Patients with a history of hypertension are allowed, provided that blood pressure is 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
- Patients with reproductive potential who do 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 patient's potential participation in a clinical trial.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01511536
|Investigational Site Number 840001
|San Francisco, California, United States |
|Investigational Site Number 840002
|New Haven, Connecticut, United States, 06510 |
|Investigational Site Number 250001
|Villejuif, France, 94805 |
|Investigational Site Number 826001
|Sutton, United Kingdom, SM2 5PT |
||Clinical Sciences & Operations
No publications provided by Sanofi
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
History of Changes
|Other Study ID Numbers:
||TCD12128, 2011-001506-96, U1111-1121-6324
|Study First Received:
||January 4, 2012
||November 7, 2013
||United States: Food and Drug Administration
Additional relevant MeSH terms:
ClinicalTrials.gov processed this record on December 05, 2013
Genital Neoplasms, Male
Neoplasms by Site
Genital Diseases, Male