XL-184+Abiraterone in Post-Chemo CRPC

A Dose Finding Clinical Trial of Cabozantinib (XL 184) Administered in Combination With Abiraterone in Castration Resistant Prostate Cancer

This research study is a Phase I clinical trial. Phase I clinical trials test the safety of an investigational drug. Phase I studies also try to define the appropriate dose of the investigational drug to use for further studies. "Investigational" means that the drug is still being studied and that research doctors are trying to find out more about it. It also means that the FDA (U.S. Food and Drug Administration) may not have approved this drug for use in participants, including people with your type of cancer.

In this research study, we are testing the safety of XL184 at different dose levels. XL184 is a new study drug, which is taken by mouth. Laboratory studies have shown that XL184 may prevent tumor growth by stopping the formation of blood vessels inside the tumor and also shrink tumors.

This drug has been used in early-stage studies and is also currently being studied in other trials. Information from those other research studies suggests that XL184 may help to slow or stop tumor growth including prostate cancer. We will also be taking blood and urine tests to look at how your body processes the drug.

Study Overview

• Status: Completed
• Conditions: Prostate Cancer
• Intervention / Treatment: Drug: Cabozantinib; Drug: Abiraterone

Detailed Description

The following procedures will be performed during this study. On Day 1 for every cycle (28 days/4 weeks)-The following will be undertaken prior to initiating study therapy and on day 1 of every subsequent cycle: A medical history, physical exam, performance status, blood tests, urine test.

Since we are looking for the highest dose of the study drug that can be administered safely without severe or unmanageable side effects in participants, not everyone who participates in this research study will receive the same dose of the study drug. The dose you get will depend on the number of participants who have been enrolled in the study before you and how well they have tolerated their doses.

We will actively monitor your condition for up to 30 days after you come off the study. If you come off study for a side effect we will monitor your condition until the resolution or stabilization of the side effect

• Study Type: Interventional
• Enrollment (Actual): 27
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Dana-Farber Cancer Institute
    • Boston, Massachusetts, United States, 02115
      • Brigham and Women's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• CRPC with up to 2 prior chemotherapy regimens
• Progressive disease on CT, MRI or bone scan per mRECIST
• Has recovered to baseline/CTCAE less than or equal to Grade 1 from toxicities related to prior treatment (except alopecia)
• Agree to use accepted barrier method of contraception

Exclusion Criteria:

• Cytotoxic chemotherapy within 3 weeks
• Prior treatment with cabozantinib or other c-MET inhibitor
• Prior therapy with a lyase inhibitor
• Concurrent use of hormonal therapies other than LHRH analogue or orchiectomy
• Received radiation therapy to thoracic cavity or GI tract within 3 months, to bone or brain metastasis within 2 weeks or to any other site within 4 weeks of first dose of study drug
• Prior treatment with a small molecular kinase inhibitor within 2 weeks of study entry
• Received another investigational product within 28 days prior to study entry
• Active brain metastases or epidural disease
• Requires concomitant treatment in therapeutic doses with warfarin or warfarin-related agents
• No uncontrolled significant intercurrent or recent illness

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment Arm; Cabozantinib and abiraterone	Drug: Cabozantinib; 28 day cycle; Other Names: XL 184; Drug: Abiraterone; 28 day cycle; Other Names: Zytiga

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Tolerated Dose	To define the MTD of cabozantinib in combination with abiraterone	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Definition of a Dosing Regimen	To define a dosing regimen of abiraterone and cabozantinib suitable for further evaluation based on long term toxicity and efficacy data	2 years

Collaborators and Investigators

• Sponsor: Dana-Farber Cancer Institute
• Investigators: Principal Investigator: Christopher Sweeney, MBBS, Dana-Farber Cancer Institute

Study record dates

Study Major Dates

• Study Start (Actual): April 3, 2012
• Primary Completion (Actual): December 31, 2014
• Study Completion (Actual): July 1, 2021

Study Registration Dates

• First Submitted: April 8, 2012
• First Submitted That Met QC Criteria: April 8, 2012
• First Posted (Estimate): April 10, 2012

Study Record Updates

• Last Update Posted (Actual): August 6, 2021
• Last Update Submitted That Met QC Criteria: August 5, 2021
• Last Verified: August 1, 2021

More Information

Terms related to this study

• Keywords: Castration Resistant; Post Chemotherapy
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Prostatic Neoplasms
• Other Study ID Numbers: 11-441

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO