Cabozantinib Plus Docetaxel and Prednisone for Advanced Prostate Cancer

Prostatic Neoplasms Clinical Trial

Official title: A Phase I and Randomized Phase II Multicenter Study of Cabozantinib (XL184) Plus Docetaxel and Prednisone in Metastatic Castrate Resistant Prostate Cancer

Status Completed

Clinical Trial Summary

Background:

• Cabozantinib is a drug that slows the growth of blood vessels that feed tumors. It is approved for medullary thyroid cancer. However, studies have shown that prostate tumors respond to it. Docetaxel and prednisone are standard treatments for advanced prostate cancer. Researchers want to see if adding cabozantinib to these two drugs can be a safe and effective treatment for this type of cancer.

Objectives:

• To test the safety and effectiveness of cabozantinib with standard treatments for advanced prostate cancer.

Eligibility:

• Individuals at least 18 years of age who have advanced prostate cancer that has not responded to standard treatments.

Design:

• Participants will be screened with a physical exam and medical history. Blood and urine samples will be collected. Imaging studies will also be performed.

• Participants will receive the cancer drugs over 21-day cycles of treatment. They will take docetaxel and cabozantinib on day 1 of each cycle. Each docetaxel infusion will take about 1 hour. They will also take prednisone by mouth twice each day.

• Treatment will be monitored with frequent blood tests and imaging studies.

• Participants will continue to take the study drugs for as long as their cancer does not worsen and side effects are not too severe.

Clinical Trial Description

Background:

• Docetaxel is established as first-line chemotherapy in patients with metastatic castrate resistant prostate cancer (CRPC). However; it is increasingly recognized that combining docetaxel with other agents of clinical activities without overlapping toxicities could simultaneously target different cellular signaling pathways vital for tumor survival, producing either additive or synergistic activities.

• Inhibition of angiogenesis, either as a stand-alone approach or in combination with chemotherapy, has demonstrable antitumor efficacy against CRPC and there are several antiangiogenic agents that are now in clinical trials in this population of patients.

• Cabozantinib (XL184) was developed as an inhibitor of both angiogenesis and of its resistance mechanism. It is an inhibitor of multiple receptor tyrosine kinases including tyrosine-protein kinase Met (c-Met), vascular endothelial growth factor receptor 2 (VEGFR2) and rearranged during transfection (RET).

• In single agent clinical studies, cabozantinib demonstrated, broad anti-tumor activities across many solid tumor types.

Objectives:

• To determine the safety profile of cabozantinib in combination with docetaxel and prednisone, and to determine the maximal tolerated dose (MTD) as recommended phase II dose in combination with docetaxel

• To determine the relative efficacy (in terms of progression free survival (PFS)) of docetaxel and cabozantinib compared to docetaxel alone

Eligibility:

• Patients must have progressive metastatic CRPC. There must be radiographic evidence of disease after primary treatment with surgery or radiotherapy. If patients had been on flutamide, they must have disease progression at least 4 weeks after withdrawal. Patients on bicalutamide or nilutamide must have progression at least 6 weeks after withdrawal. Withdrawal criteria apply only to patients on the above anti-androgens for at least the prior 6 months.

• Patients must be at least 18 years of age and able to give informed consent.

• Patients in the Phase II portion of the study must have progressed on abiraterone or enzalutamide

Design:

• The initial phase I portion of this study will test fixed dose docetaxel and prednisone in combination with cabozantinib at three escalating doses. Using a standard 3 + 3 design, three patients will initially be treated at each dose level until MTD has been defined.

• An expansion cohort will then be enrolled at the MTD to further characterize safety, toxicity and pharmacokinetic data and to obtain preliminary information on the efficacy of the combination treatment.

• In Phase II, patients will be enrolled to a randomized two-arm cohort comparing docetaxel in combination with cabozantinib to docetaxel alone with a primary endpoint of PFS.

• The accrual ceiling for the study, including the Phase I dose escalation and the expansion phases as well as the Phase II randomized phase, is set at 81. ;

Related Conditions & MeSH terms

• Prostatic Neoplasms

• NCT number: NCT01683994
• Study type: Interventional
• Source: National Institutes of Health Clinical Center (CC)
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: September 7, 2012
• Completion date: January 16, 2019