Sirolimus, Docetaxel, and Carboplatin in Treating Patients With Metastatic Castration-Resistant Prostate Cancer

Metastatic Prostate Carcinoma Clinical Trial

Official title: A Phase 1-2 Study of Sirolimus, Docetaxel and Carboplatin for Treatment of Patients With Metastatic, Castration Resistant Prostate Cancer: (Rapamycin Inhibition of DDSP [RID])

Status Terminated

Clinical Trial Summary

This partially randomized phase I/II trial studies the side effects and how well sirolimus works when given together with docetaxel and carboplatin in treating patients with castration-resistant prostate cancer that has spread to other places in the body (metastatic). Biological therapies, such as sirolimus, use substances made from living organisms that may stimulate or suppress the immune system in different ways and stop tumor cells from growing. Drugs used in chemotherapy, such as docetaxel and carboplatin, 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 sirolimus together with docetaxel and carboplatin may kill more tumor cells.

Clinical Trial Description

PRIMARY OBJECTIVES:

I. To define the recommended phase 2 dose (RP2D) of sirolimus combined with docetaxel and carboplatin in the treatment of metastatic castration resistant prostate cancer (CRPC). (Phase I)

II. To assess the effectiveness of sirolimus in suppressing the induction of the deoxyribonucleic acid (DNA) damage secretory component WNT16B in tumor stroma following docetaxel and carboplatin. (Phase II)

EXPLORATORY OBJECTIVES:

I. To assess maximal prostate-specific antigen (PSA) response to sirolimus combined with docetaxel and carboplatin. (Phase I)

II. To assess PSA response duration to sirolimus combined with docetaxel and carboplatin. (Phase I)

III. To assess response of measurable disease. (Phase I)

IV. To assess time to progression of bone lesions or measurable disease (Response Evaluation Criteria in Solid Tumors [RECIST] 1.1). (Phase I)

V. To assess effect of sirolimus with docetaxel and carboplatin on DNA damage surrogates in cancer associated stroma compared to untreated and docetaxel and carboplatin treated stroma. (Phase I)

VI. To assess maximal PSA response to sirolimus combined with docetaxel and carboplatin. (Phase II)

VII. To assess PSA response duration to sirolimus combined with docetaxel and carboplatin. (Phase II)

VIII. To assess response of measurable disease (RECIST 1.1). (Phase II)

IX. To assess time to progression of bone lesions or measurable disease (RECIST 1.1). (Phase II)

X. To assess toxicity of the RP2D dose of sirolimus with docetaxel and carboplatin. (Phase II)

XI. To determine the effect of docetaxel and carboplatin therapy on the DNA damage secretory program (DDSP) in serum. (Phase II)

XII. To determine response to sirolimus, docetaxel and carboplatin in tumors with mutation of DNA repair pathway genes (breast cancer gene 2 [BRCA2], ataxia telangiectasia mutated [ATM] and other Fanconi anemia complementation groups [FANC] pathway members). (Phase II)

XIII. To correlate the presence of DNA repair pathway mutations in circulating tumor cells (CTC) and circulating tumor DNA (ctDNA) with tumor biopsy and correlate changes in CTC number and ctDNA mutation levels with clinical responses. (Phase II)

OUTLINE: This is a phase I, dose de-escalation study of sirolimus followed by a phase II study.

PHASE I: Patients receive sirolimus orally (PO) on day -2*. Patients also receive docetaxel intravenously (IV) over 30-60 minutes and carboplatin IV over 30-60 minutes on day 1. Treatment repeats every 21 days for 10 cycles in the absence of disease progression or unacceptable toxicity.

PHASE II: Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive docetaxel IV over 30-60 minutes and carboplatin IV over 30 minutes on day 1. Beginning in cycle 2 and continuing in subsequent cycles, patients also receive sirolimus PO on day -2. Treatment repeats every 21 days for 10 cycles in the absence of disease progression or unacceptable toxicity.

ARM II: Patients receive sirolimus PO on day -2. Patients also receive docetaxel IV over 30-60 minutes and carboplatin IV over 30-60 minutes on day 1. Treatment repeats every 21 days for 10 cycles in the absence of disease progression or unacceptable toxicity.

• NOTE: Patients receive sirolimus 2 days prior to chemotherapy day 1 (there is no day 0). ;

Related Conditions & MeSH terms

• Carcinoma
• Castration-Resistant Prostate Carcinoma
• Metastatic Malignant Neoplasm in the Bone
• Metastatic Prostate Carcinoma
• Neoplasms
• Prostatic Neoplasms
• Stage IV Prostate Cancer AJCC v7

• NCT number: NCT02565901
• Study type: Interventional
• Source: University of Washington
• Status: Terminated
• Phase: Phase 1/Phase 2
• Start date: February 29, 2016
• Completion date: June 16, 2020