Docetaxel Versus Cabazitaxel Post Abiraterone or Enzalutamide

NCT ID: NCT03764540

Last Updated: 2025-04-13

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 57 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-04-01
• Study Completion Date: 2024-12-31

Brief Summary

Prostate cancer (PCa) is the most frequently diagnosed cancer in Canadian men. While the majority of PCa is slow growing and responds well to first line treatment, a proportion of cases (10%) progress to metastatic form resulting in more than 4 000 deaths annually in Canada and 250 000 worldwide. Currently, first line treatment for PCa includes surgery, radiation and androgen deprivation therapy (ADT). A rapid evolution in the understanding of disease biology, combined with approvals of new therapies including immunotherapy, novel chemotherapy, hormonal agents and a bone calcium matrix-targeted radionuclide, along with further drugs in development, have made treatment decisions for metastatic castration-resistant prostate cancer (mCRPC) increasingly complex and challenging.

This is a Phase II Study of Cabazitaxel plus prednisone in patients with metastatic castration-resistant prostate cancer (mCRPC). The current study is designed to determine if cabazitaxel will improve progression free survival (PFS) or overall survival (OS).

This study will enroll patients with mCRPC, who have been previously treated and progressed under docetaxel or abiraterone regimen.

Patients must meet the study eligibility criteria and must be competent to give informed consent.

Detailed Description

This is a prospective, multicenter, national, randomized, open label study, comparing the efficacy of cabazitaxel at 25 mg/m² plus prednisone (Arm A) over docetaxel at 75mg/m2 plus prednisone (Arm B) after enzalutamide at 160 mg once daily or abiraterone acetate at 1000 mg once daily plus prednisone in chemotherapy-naïve patients with mCRPC who have progressed on abiraterone acetate or enzalutamide.

Each patient will be treated until disease progression, unacceptable toxicity, or patient's refusal of further study treatment.

All eligible patients will be randomly assigned to either arm A or B in a 1:1 proportion.

Conditions

Metastatic Prostate Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Cabazitaxel plus prednisone

Cabazitaxel: Single-dose vial, containing a total of 60 mg of cabazitaxel expressed as anhydrous and solvent-free basis, per 1.5 mL of solution. Cabazitaxel will be administered by IV route Prednisone will be administered orally, 5 mg twice daily (10 mg per day total dose).

Prednisone will be administered by oral route

Group Type: EXPERIMENTAL

Cabazitaxel plus prednisone

Intervention Type: DRUG

Cabazitaxel 25 mg/m² intravenously on day 1 of each cycle, plus prednisone 10 mg orally given daily.

A cycle is defined as a 3-weeks period for a maximum of 10 cycles.

Docetaxel plus prednisone

Docetaxel is formulated in polysorbate 80 and commercially available as 80 mg/2.0 mL single-dose vials with accompanying diluent (13% ethanol in water for injection) for IV use.

Prednisone will be administered orally, 5 mg twice daily (10 mg per day total dose).

Prednisone will be administered by oral route

Group Type: ACTIVE_COMPARATOR

Docetaxel plus prednisone

Intervention Type: DRUG

Docetaxel 75 mg/m² intravenously on day 1 of each cycle, plus prednisone 10 mg orally given daily.

A cycle is defined as a 3-weeks period for a maximum of 10 cycles.

Interventions

Cabazitaxel plus prednisone

Cabazitaxel 25 mg/m² intravenously on day 1 of each cycle, plus prednisone 10 mg orally given daily.

A cycle is defined as a 3-weeks period for a maximum of 10 cycles.

Intervention Type: DRUG

Docetaxel plus prednisone

Docetaxel 75 mg/m² intravenously on day 1 of each cycle, plus prednisone 10 mg orally given daily.

A cycle is defined as a 3-weeks period for a maximum of 10 cycles.

Intervention Type: DRUG

Other Intervention Names

Experimental; Active Comparator

Eligibility Criteria

Inclusion Criteria

• Diagnosis of histologically or cytologically confirmed prostate adenocarcinoma.
• Metastatic disease.
• Progressive disease (PD) while receiving AR targeted therapy with abiraterone acetate or enzalutamide by at least one of the following:
• Progression in measurable disease (RECIST 1.1 criteria). Patient with measurable disease must have at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded). Each lesion must be at least 10 mm when measured by computed tomography (CT) [CT scan thickness no greater than 5 mm] or magnetic resonance imaging (MRI). Lymph nodes should be ≥ 15 mm in short axis. As defined by PCWG2, if lymph node metastasis is the only evidence of metastasis, it must be ≥ 20 mm in diameter when measured by spiral CT or MRI. Previously irradiated lesions, primary prostate lesion and bone lesions will be considered non-measurable disease, and/or
• Appearance of 2 or more new bone lesions. They must be confirmed by other imaging modalities (CT; MRI) if ambiguous results (PCWG2), and/or
• Rising PSA defined (PCWG2) as at least two consecutive rises in PSA to be documented over a reference value (measure 1) taken at least one week apart. The first rising PSA (measure 2) should be taken at least 7 days after the reference value. A third confirmatory PSA measure is required (2nd beyond the reference level) to be greater than the second measure and it must be obtained at least 7 days after the 2nd measure. If this is not the case, a fourth PSA measure is required to be taken and be greater than the 2nd measure. The third (or the fourth) confirmatory PSA should be taken within 4 weeks prior to randomization.
• A PSA value of at least 2 ng/mL is required at study entry.
• Effective castration (serum testosterone levels ≤0.5 ng/mL).
• Prior AR targeted therapy (abiraterone acetate or enzalutamide) must be stopped at least 2 weeks before study treatment.
• Signed written informed consent.

Exclusion Criteria

Related to methodology:

• Prior chemotherapy for prostate cancer, except estramustine and except adjuvant/neoadjuvant treatment completed >3 years ago. Prior treatment with sipuleucel T immunotherapy is allowed at the condition patient did not received prior chemotherapy. No further anti-cancer therapy after the previous AR targeted therapy and before inclusion.
• Less than 28 days elapsed from prior treatment with radiotherapy or surgery to the time of randomization.
• Prior isotope therapy, whole bony pelvic radiotherapy, or radiotherapy to >30% of bone marrow.
• Less than 18 years (or country's legal age of majority if the legal age is >18 years).
• Eastern Cooperative Oncology Group (ECOG) performance status >1.
• History of brain metastases, uncontrolled spinal cord compression, or carcinomatous meningitis or new evidence of brain or leptomeningeal disease.
• Prior malignancy. Adequately 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 treatment has been completed ≥5 years ago and from which the patient has been disease-free for ≥5 years.
• Participation in another clinical trial and any concurrent treatment with any investigational drug within 30 days prior to randomization.
• Any of the following within 3 months prior to randomization: treatment resistant peptic ulcer disease, erosive esophagitis or gastritis, infectious or inflammatory bowel disease, diverticulitis, pulmonary embolism, or other uncontrolled thromboembolic event.
• Acquired immunodeficiency syndrome (AIDS-related illnesses) or known HIV disease requiring antiretroviral treatment.
• Any severe acute or chronic medical condition which could impair the ability of the patient to participate to the study or interfere with interpretation of study results, or patient unable to comply with the study procedures.
• Patients with reproductive potential who do not agree to use accepted and effective method of contraception during the study treatment period and up to 6 months after the last administered dose. The definition of "effective method of contraception" will be based on the investigator's judgment.

Related to study treatment

• Known allergies, hypersensitivity or intolerance to prednisone. History of hypersensitivity to docetaxel or polysorbate 80.
• Known history of mineralocorticoid excess or deficiency.
• Unable to swallow a whole tablet or capsule
• Inadequate organ and bone marrow function as evidenced by:

1. Hemoglobin <10.0 g/dL

2. Absolute neutrophil count <1.5 x 109/L

3. Platelet count <100 x 109/L

4. AST/SGOT and/or ALT/SGPT >1.5 x ULN;

5. Total bilirubin >1.0 x ULN

6. Potassium <3.5 mmol/L

7. Serum albumin <3.0 g/dL

8. Child-Pugh Class B and C

9. Serum Creatinine ≤ 1.5 x ULN,

• Contraindications to the use of corticosteroid treatment.
• Symptomatic peripheral neuropathy grade >2 (National Cancer Institute Common Terminology Criteria for Adverse Events [NCI CTCAE] v.4.0).
• 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 (NYHA) Class III or IV heart disease or cardiac left ventricular ejection fraction (LVEF) measurement of <50% at baseline.

• Minimum Eligible Age: 18 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

Genzyme, a Sanofi Company

INDUSTRY

Sponsor Role: collaborator

Centre hospitalier de l'Université de Montréal (CHUM)

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

fred Saad, MD

Role: PRINCIPAL_INVESTIGATOR

CHUM

Locations

Centre Hospitalier de l'Université de Montréal

Montreal, Quebec, Canada

Countries

Canada

Other Identifiers

MP-02-2018-7545

Identifier Type: -

Identifier Source: org_study_id