Docetaxel Versus Cabazitaxel Post Abiraterone or Enzalutamide

NCT03764540 | Terminated Phase 2

• 1 other identifier: MP-02-2018-7545
• Study Type: interventional
• Target: 57
• Locations: 1 country
• Sites: 1

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.

Conditions

Metastatic Prostate Cancer

Outcome Measures

Primary Outcomes (1)

• PSA response rate at 6 and 12 months

  Change from baseline PSA level of at least 50%, PSA partial response is defined as a ≥ 50% decline in PSA from cycle 1 day 1 (baseline) PSA value. This PSA change must be confirmed as sustained by a second PSA value obtained ≥ 3 weeks later.

  through study completion, an average of 1 year

Secondary Outcomes (7)

• Radiological progression-free survival (rPFS)

  through study completion, an average of 1 year

• Overall Survival

  through study completion, an average of 1 year

• Time to PSA progression (TTPP)

  through study completion, an average of 1 year

• Tumor response

  through study completion, an average of 1 year

• Duration of tumor response

  hrough study completion, an average of 1 year

Study Arms (2)

Cabazitaxel plus prednisone

EXPERIMENTAL

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

Drug: Cabazitaxel plus prednisone

Docetaxel plus prednisone

ACTIVE COMPARATOR

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

Drug: Docetaxel plus prednisone

Interventions

Cabazitaxel plus prednisone 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.

Also known as: Experimental

Cabazitaxel plus prednisone

Docetaxel plus prednisone 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.

Also known as: Active Comparator

Docetaxel plus prednisone

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• Related to methodology:
• 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.

Sponsors & Collaborators

• Centre hospitalier de l'Université de Montréal (CHUM): lead
• Genzyme, a Sanofi Company: collaborator

Study Sites (1)

Centre Hospitalier de l'Université de Montréal

Montreal, Quebec, H2X 3E4, Canada

Location

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

cabazitaxel; Prednisone; Docetaxel

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)

Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Study Officials

• fred Saad, MD

  CHUM

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 3, 2018
• First Posted: December 5, 2018
• Study Start: April 1, 2019
• Primary Completion: December 31, 2024
• Study Completion: December 31, 2024
• Last Updated: April 13, 2025

Record last verified: 2025-01

Locations

CA (1)