This phase III trial compares the effect of adding carboplatin to the standard of care chemotherapy drug cabazitaxel versus cabazitaxel alone in treating prostate cancer that keeps growing even when the amount of testosterone in the body is reduced to very low levels (castrate-resistant) and that has spread from where it first started (primary site) to other places in the body (metastatic). Carboplatin is in a class of medications known as platinum-containing compounds. Carboplatin works by killing, stopping or slowing the growth of tumor cells. Chemotherapy drugs, such as cabazitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Prednisone is often given together with chemotherapy drugs. Prednisone is in a class of medications called corticosteroids. It is used to reduce inflammation and lower the body's immune response to help lessen the side effects of chemotherapy drugs and to help the chemotherapy work. Giving carboplatin with the standard of care chemotherapy drug cabazitaxel may be better at treating metastatic castrate-resistant prostate cancer.
PRIMARY OBJECTIVES: I. To compare radiographic progression free survival (rPFS) between the two treatment arms in the subset of aggressive variant prostate cancer - molecular-pathologic signature (AVPC-MS)-positive participants. II. If the AVPC-MS positive test is statistically significant, test in AVPC-MS negative participants whether the combination of carboplatin and cabazitaxel improves rPFS. SECONDARY OBJECTIVES: I. To compare overall survival (OS) between the two treatment arms, stratified by AVPC-MS positive versus (vs.) negative. II. To compare response rates for prostate specific antigen (PSA), total alkaline phosphatase, and Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 between the two treatment arms, stratified by AVPC-MS positive vs. negative. III. To compare rPFS between the two treatment arms for the full trial. IV. To compare rPFS between the two treatment arms for the AVPC-MS negative group in the absence of a positive treatment effect in the AVPC-MS positive group. V. To compare progression free survival (PFS) between the two treatment arms, stratified by AVPC-MS positive vs. negative. VI. To compare toxicities between the two arms in participants who receive any treatment on study. BANKING OBJECTIVES: I. To bank specimens for future correlative studies. OUTLINE: Patients are randomized to 1 of 2 arms. ARM 1: Patients receive cabazitaxel intravenously (IV) over 60 minutes on day 1 of each cycle and prednisone orally (PO) twice daily (BID) on days 1-21 of each cycle. Cycles repeat every 21 days for up to 10 cycles in the absence of disease progression or unacceptable toxicity. ARM 2: Patients receive cabazitaxel and carboplatin IV over 60 minutes on day 1 of each cycle and prednisone PO BID on days 1-21 of each cycle. Cycles repeat every 21 days for up to 10 cycles in the absence of disease progression or unacceptable toxicity. All patients undergo blood sample collection, bone scan, computed tomography (CT), positron emission tomography (PET), or magnetic resonance imaging (MRI) throughout the trial and chest radiography (x-ray) before randomization. After completion of study treatment, patients are followed every 12 weeks for 1 year after randomization, and then every 26 weeks for up to 4 years after randomization or until death, whichever occurs first.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
528
Undergo blood sample collection
Undergo bone scan
Given IV
Given IV
Undergo chest x-ray
Undergo CT or PET/CT
Undergo MRI
Undergo PET/CT
Given PO
Highlands Oncology Group - Fayetteville
Fayetteville, Arkansas, United States
RECRUITINGHighlands Oncology Group - Rogers
Rogers, Arkansas, United States
RECRUITINGHighlands Oncology Group
Springdale, Arkansas, United States
RECRUITINGTibor Rubin VA Medical Center
Long Beach, California, United States
Radiographic progression-free survival (rPFS)
Will be assessed using response evaluation criteria in solid tumors (RECIST 1.1), progression of bone lesions using Prostate Cancer Working Group 2 (PCWG2) criteria, or occurrence of death due to any cause. RECIST 1.1 progression requires at least a 20% increase in the sum of diameters of target lesions and/or unequivocal progression of existing non-target lesions. PCWG2 bone lesion progression requires appearance of two or more new lesions seen on bone scan compared with bone scan at randomization.
Time frame: From date of randomization to the first documentation of rPFS event, assessed up to 5 years
Prostate specific antigen (PSA) response
Percentage of the subset of participants with a randomization PSA level of at least 5.0 ng/ml with a greater than 50% decrease in measurable values of PSA during treatment from the value measured at randomization.
Time frame: From study entry to first occurrence of rPFS or clinical progression, assessed up to 5 years
Alkaline phosphatase response
Percentage of participants with a greater than 50% decrease in measurable values of alkaline phosphatase during treatment from their value at randomization.
Time frame: From study entry to first occurrence of rPFS or clinical progression, assessed up to 5 years
RECIST response
Percentage of the subset of participants with measurable disease with an overall objective tumor response defined as a partial response (PR) or complete response (CR) according to RECIST version 1.1.
Time frame: From study entry to first occurrence of rPFS or clinical progression, assessed up to 5 years
Progression-free survival
Will be descriptively characterized between the two treatment arms. Survival curves will be estimated by the Kaplan-Meier method and a log-rank test will be used to compare both overall survival (OS) and PFS between the treatment arms, stratified by aggressive variant prostate cancer - molecular-pathologic signature (AVPC-MS) status.
Time frame: From study entry to first occurrence of rPFS or clinical progression, assessed up to 5 years
OS
Participants known to be alive are censored at date of last contact. Will be descriptively characterized between the two treatment arms. Survival curves will be estimated by the Kaplan-Meier method and a log-rank test will be used to compare both OS and PFS between the treatment arms, stratified by AVPC-MS status.
Time frame: From date of randomization to date of death due to any cause, assessed up to 5 years
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Beebe Medical Center
Lewes, Delaware, United States
RECRUITINGBeebe South Coastal Health Campus
Millville, Delaware, United States
RECRUITINGHelen F Graham Cancer Center
Newark, Delaware, United States
RECRUITINGMedical Oncology Hematology Consultants PA
Newark, Delaware, United States
RECRUITINGChristiana Care Health System-Christiana Hospital
Newark, Delaware, United States
RECRUITINGBeebe Health Campus
Rehoboth Beach, Delaware, United States
RECRUITING...and 164 more locations