Abiraterone Acetate and Antiandrogen Therapy With or Without Cabazitaxel and Prednisone in Treating Patients With Metastatic, Castration-Resistant Prostate Cancer Previously Treated With Docetaxel

Castration-Resistant Prostate Carcinoma Clinical Trial

Official title: Cabazitaxel With Abiraterone Versus Abiraterone Alone Randomized Trial for Extensive Disease Following Docetaxel: The CHAARTED2 Trial

Status Active, not recruiting

Clinical Trial Summary

This randomized phase II trial studies how well abiraterone acetate and antiandrogen therapy, with or without cabazitaxel and prednisone, work in treating patients with castration-resistant prostate cancer previously treated with docetaxel that has spread to other parts of the body. Androgens can cause the growth of prostate cancer cells. Hormone therapy using abiraterone acetate and antiandrogen therapy may fight prostate cancer by lowering and/or blocking the use of androgens by the tumor cells. Drugs used in chemotherapy, such as cabazitaxel and prednisone, 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. Giving abiraterone acetate and antiandrogen therapy with or without cabazitaxel and prednisone may help kill more tumor cells.

Clinical Trial Description

PRIMARY OBJECTIVES:

I. To assess whether the addition of 6 cycles of cabazitaxel to abiraterone acetate in patients with castration-resistant prostate cancer (CRPC) that have previously received docetaxel and androgen deprivation therapy (ADT) for hormone-sensitive prostate cancer (HSPC) can improve progression-free survival (PFS) compared to abiraterone acetate alone.

SECONDARY OBJECTIVES:

I. To assess whether the addition of 6 cycles of cabazitaxel to abiraterone acetate in patients with CRPC that have previously received docetaxel and ADT for HSPC can increase the percentage of change in prostate-specific antigen (PSA) from baseline to week 12 of treatment as well as the maximum decline in PSA that occurs at any point after treatment compared to abiraterone acetate alone.

II. To assess whether the addition of 6 cycles of cabazitaxel to abiraterone acetate in patients with CRPC that have previously received docetaxel for HSPC can prolong time to PSA progression compared to abiraterone acetate alone.

III. To assess whether the addition of 6 cycles of cabazitaxel to abiraterone acetate in patients with CRPC that have previously received docetaxel for HSPC can improve radiographic response (per Response Evaluation Criteria in Solid Tumors [RECIST] 1.1) compared to abiraterone acetate alone.

IV. To assess whether the addition of 6 cycles of cabazitaxel to abiraterone acetate in patients with CRPC that have previously received docetaxel and ADT for HSPC can prolong the overall survival (OS) compared to abiraterone acetate alone.

V. To assess safety and tolerability of the combination of 6 cycles of cabazitaxel and abiraterone acetate.

TERTIARY OBJECTIVES:

I. To examine whether patients with circulating tumor cells (CTCs) positive for AR-V7 at baseline have a longer radiographic or clinical PFS to the combination of cabazitaxel and abiraterone acetate vs. abiraterone acetate alone.

II. To examine whether the addition of cabazitaxel to abiraterone acetate can change the AR-V7 status of patients who are positive at study entry.

III. To examine whether the addition of cabazitaxel to abiraterone acetate has any impact on future development of AR-V7 positivity at the time of disease progression.

IV. To assess if the changes in total tumor burden from baseline to week 12 as assessed with sodium fluoride (NaF) positron emission tomography (PET)/computed tomography (CT) will differ between two arms.

V. To correlate total tumor burden at the baseline as assessed with NaF PET/CT with the PFS.

VI. To correlate heterogeneity of response from baseline to week 12 as assessed with NaF PET/CT with the PFS.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM A: Patients receive abiraterone acetate orally (PO) once daily (QD) on days 1-21, prednisone PO twice daily (BID) on days 1-21. Courses of abiraterone acetate and prednisone repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients receive cabazitaxel intravenously (IV) over 1 hour on day 1, and treatment with cabazitaxel repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients also receive standard of care antiandrogen therapy with either luteinizing hormone-releasing hormone (LHRH) agonist or antagonist, or surgical castration with bilateral orchiectomy.

ARM B: Patients receive abiraterone acetate and prednisone as in Arm A. Patients also receive standard of care antiandrogen therapy with either LHRH agonist or antagonist, or surgical castration with bilateral orchiectomy.

After completion of study treatment, patients are followed up every 3 or 6 months and then annually for up to 5 years. ;

Related Conditions & MeSH terms

• Carcinoma
• Castration Levels of Testosterone
• Castration-Resistant Prostate Carcinoma
• Metastatic Prostate Carcinoma in the Soft Tissue
• Prostate Carcinoma Metastatic in the Bone
• Prostatic Neoplasms
• Stage IV Prostate Adenocarcinoma AJCC v7

• NCT number: NCT03419234
• Study type: Interventional
• Source: Eastern Cooperative Oncology Group
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: April 26, 2018
• Completion date: April 1, 2026