A Phase I/II Study of TRC105 in Metastatic Castrate Resistant Prostate Cancer (CRPC)
- Currently, there is no curative therapy for metastatic castrate-resistant prostate cancer (CRPC), a leading cause of death in men. However, researchers are exploring new treatments that involve drugs that prevent angiogenesis (the process by which new blood vessels are formed) and can slow or prevent tumor growth.
- TRC105 is an experimental drug that blocks angiogenesis, and has been studied for possible use in treating different kinds of cancer. However, it has not been validated to treat prostate cancer in general or CRPC in particular.
- To determine the effects of TRC105 as a treatment for CRPC
- To determine the safety and effectiveness of TRC105 in treating CRPC
- Men at least 18 years of age who have been diagnosed with castrate-resistant prostate cancer for which existing treatments have not been effective.
- Eligible individuals will have a series of blood and other tests to determine their suitability for participating in the study.
- Participants will receive intravenous infusions of TRC105 in a 28-day treatment cycle. Infusions will be given on Day 1 and Day 14 of each cycle.
- Participants will receive different doses of TRC105 depending on when they enter the study, up to a maximum tolerated dose or optimum treatment dose.
- Frequent blood and urine tests will be performed during treatment, as well as other tests of cancer progression as directed by the study doctors. Participants will receive medicines to help prevent possible adverse side effects of TRC105, such as allergic reaction to the drug.
- Participants will continue treatment with TRC105 until they or the study team decides that the medication is not beneficial. No additional testing will be required unless participants discontinue the treatment because of side effects (which the study doctors will follow until the side effects are resolved).
Metastatic Castrate Resistant Prostate Cancer
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase I/II Study of TRC105 in Metastatic Castrate Resistant Prostate Cancer (CRPC)|
- Define the maximum tolerable dose (MTD) of TRC105 given every two weeks. Determine if single-agent TRC105, when administered at MTD to patients with CRPC, is associated with a 6-month progression-free survival probability of 30%. [ Time Frame: 6 month progression - free survival ] [ Designated as safety issue: Yes ]
- Define the dose-limiting toxicities and toxicity profile of TRC105 given every two weeks. Evaluate time to disease progression, overall response rate, and overall survival. [ Time Frame: Evaluate time to disease progression, overall response rate and overall survival ] [ Designated as safety issue: No ]
|Study Start Date:||February 2010|
|Estimated Study Completion Date:||March 2014|
|Estimated Primary Completion Date:||March 2014 (Final data collection date for primary outcome measure)|
Active Comparator: Arm 1
No prior chemotherapy or antiangiogenic therapy
Active Comparator: Arm 2
Evidence of disease progression despite prior docetaxel and bevacizumab. Any number of treatment lines is available.
- Inhibition of angiogenesis has demonstrable antitumor efficacy against castrate-resistant prostate cancer (CRPC). TRC105 is a human/murine chimeric IgG1 kappa monoclonal antibody that binds to human CD105 (endoglin), thus inhibiting angiogenesis and tumor growth. Data from an ongoing phase I clinical trial suggest that TRC105 is well tolerated with evidence of clinical efficacy in patients with metastatic CRPC.
- Define the maximum tolerable dose (MTD) of TRC105 given every one to two weeks.
- Determine if single-agent TRC105, when administered at 20 mg/kg IV every two weeks (the phase I MTD) to patients with CRPC, is associated with a 6-month progression-free survival probability of 30%
- Define the dose-limiting toxicities and toxicity profile of TRC105 given every one to two weeks
- Evaluate time to disease progression, overall response rate and overall survival.
- Describe the prostate specific antigen (PSA) response rate to therapy with TRC105
- Characterize the pharmacokinetics of TRC105
- Demonstrate a biologic effect of TRC105 in the patient and, when possible, on the tumor via laboratory evaluation of the molecular markers of angiogenesis before and after drug administration respectively
- Progressive, castrate-resistant, metastatic adenocarcinoma of the prostate
- ECOG less than or equal to 2
- An initial single-arm, phase I dose escalation study open to all patients with progressive metastatic CRPC. The study will evaluate patients in five cohorts of escalating dose levels. A maximum of 30 patients will be needed to complete the phase I evaluation.
Following completion of the phase I study will be a two-stage, phase II study that will be conducted separately in the following two arms:
- Chemotherapy-na(SqrRoot) ve for metastatic disease (no prior antiangiogenic therapy)
- Post-docetaxel disease progression
- In each arm, the primary objective will be to determine if a 6 month progression free survival probability of 30.0% can be identified.
- Initially, 12 patients will be enrolled in each stratum and evaluated for progression. If 2 or more are progression-free at 6 months, then enrollment will continue until a full 35 patients have been enrolled in that stratum. Enrollment may continue to the other stratum if one stratum has ended accrual.
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike|
|Bethesda, Maryland, United States, 20892|
|Principal Investigator:||William L Dahut, M.D.||National Cancer Institute (NCI)|