E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10060862 |
E.1.2 | Term | Prostate cancer |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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
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E.2.2 | Secondary objectives of the trial |
To characterize the safety profile of the combination
To evaluate the pharmacokinetic profile of cabazitaxel and abiraterone acetate in the proposed combination and dosing schedule
To assess preliminary antitumor activity of the combination in terms of progression-free survival, time to PSA progression free survival and and objective response rate, and overall survival
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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 ABIa for at least 3 months and should continue treatment with ABIa 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:
a) Increase in non-measureable disease or measurable disease, and/or
b) 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 cancerEffective castration (serum testosterone levels ≤0.50 ng/mL) by orchiectomy and/or luteinizing hormone releasing hormone agonists /antagonist.
a) 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.
b) Prior anti-androgen therapy should be stopped before enrollment Eastern Cooperative Oncology Group performance status: 0 – 1
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E.4 | Principal exclusion criteria |
Previous treatment with mitoxantrone or CBZ.
Prior bone-seeking radio-isotope therapy (patients treated with Radium223 are not excluded from the study). Radiotherapy to ≥30% of bone marrow.
Adverse events (excluding alopecia and those listed in the specific exclusion criteria) from any prior anticancer therapy of grade >1(National Cancer Institute Common Terminology Criteria v4.03) 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 ABIa 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 to the study
Other concurrent serious illness or medical conditions
Absence of signed and dated Institutional Review Board -approved 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 and biochemical indices as evidenced by:
a) Hemoglobin <10.0 g/dL
b) Absolute neutrophil count <1.5 x 10^9/L
c) History of primary G-CSF prophylactics required for prior chemotherapy
d) Platelet count < 100 x 10^9/L
e) Potassium <3.5 mmol/L
f) AST/SGOT and/or ALT/SGPT > 2.5 x the institutions upper limit of normal
g) Total bilirubin > 1.0 x the institutions upper limit of normal
h) Serum albumin < 3.0 g/dL
i) Child-Pugh class B&C
j) Serum Creatinine > 1.5 x the institutions upper limit of normal. If creatinine 1.0 - 1.5 x the institutions upper limit of normal, creatinine clearance will be calculated; Creatinine clearance < 60 mL/min/1.73m2 will exclude the patient
Contraindications to the use of corticosteroid treatment.
Symptomatic peripheral neuropathy grade > 1
Concurrent treatment with strong inducers or strong inhibitors of cytochrome P450 3A4, or patients planning to receive these treatments
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, in the Investigator's medical opinion, who do not agree to use accepted and effective method of contraception in conjunction with their partner(s) during the study treatment period. The definition of "effective method of contraception" will be based on country-specific regulatory requirements, and documented in the Informed Consent Form. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Maximum tolerated dose of cabazitaxel in combination with abiraterone acetate
PSA Response Rate |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
up to 8 months
up to 3 years |
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E.5.2 | Secondary end point(s) |
- Overall safety profile of the combination in terms of Treatment-emergent adverse events and laboratory abnormalities
- Pharmacokinetics of cabazitaxel and abiraterone in the proposed combination and dosing schedule
- Objective PFS
- PSA progression free survival
- Objective response rate
- Overall survival |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
up to 3 years
up to 1 month
up to 3 years
up to 3 years
up to 3 years
Up to 3 years |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Yes |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 2 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
France |
United Kingdom |
United States |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | 30 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 30 |