Metastatic Prostate Cancer
Conditions
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.
Interventions
DRUGCabazitaxel 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.
DRUGDocetaxel 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.
Sponsors
Genzyme, a Sanofi Company
Centre hospitalier de l'Université de Montréal (CHUM)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
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. * Adverse events (excluding alopecia and those listed in the specific
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| PSA response rate at 6 and 12 months | through study completion, an average of 1 year | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival | through study completion, an average of 1 year | Time interval from the date of randomization to the date of death due to any cause |
| Time to PSA progression (TTPP) | through study completion, an average of 1 year | Time interval between the date of randomization and the date of first documented PSA progression. |
| Tumor response | through study completion, an average of 1 year | Measurable by RECIST 1.1 |
| Radiological progression-free survival (rPFS) | through study completion, an average of 1 year | Time interval between the date of randomization and the date of the first documentation of any of the following event. Radiological tumor progression by RECIST 1.1 and PCWG2, |
| Pain response: BPI-SF pain intensity item scores | through study completion, an average of 1 year | Decrease by \<30% from baseline in the average of BPI-SF pain intensity item scores (items 3, 4, 5, and 6) observed at 2 consecutive evaluations ≥3 weeks apart without increase in analgesic usage score. |
| Time to Pain progression | through study completion, an average of 1 year | Time interval between the date of randomization and the date of the first documented pain progression |
| Duration of tumor response | hrough study completion, an average of 1 year | Time between the first evaluation at which the tumor response criteria are met and the first documentation of tumor progression. |
Countries
Canada
Outcome results
None listed