Title
A Phase III Study of Cabazitaxel with or without Carboplatin in Patients with Metastatic Castrate Resistant Prostate Cancer (MCRPC), Stratified by Aggressive Variant Signature

Description
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.

Objective
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.

Treatment 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.

Key Eligibility For full study eligibility, please see this study's clinicaltrials.gov record.

Applicable Disease Sites
Prostate

Participating Institutions
UW Health Eastpark Medical Center; UW Health University Hospital