A Phase I/II Study of TRC105 in Metastatic Castrate Resistant Prostate Cancer (CRPC)
- Conditions
- Metastatic Castrate Resistant Prostate CancerProstate Cancer
- Interventions
- Registration Number
- NCT01090765
- Lead Sponsor
- National Cancer Institute (NCI)
- Brief Summary
Background:
* 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.
Objectives:
* To determine the effects of TRC105 as a treatment for CRPC
* To determine the safety and effectiveness of TRC105 in treating CRPC
Eligibility:
- Men at least 18 years of age who have been diagnosed with castrate-resistant prostate cancer for which existing treatments have not been effective.
Design:
* 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. Participants will receive i.v. (intravenous) infusions of TRC105 every two weeks on days 1 and 15 of each 28-day cycle (cohorts 1, 2, 3, 5, and 6) and every week on days 1, 8, 15, and 22 of each 28 day cycle (cohort 4).
* 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).
- Detailed Description
Background:
- Inhibition of angiogenesis has demonstrable antitumor efficacy against castrate-resistant prostate cancer (CRPC). TRC105 is a human/murine chimeric immunoglobulin heavy constant gamma 1 (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.
Primary Objectives:
- Define the maximum tolerable dose (MTD) of TRC105 given every one to two weeks.
Secondary Objectives:
* 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
Eligibility:
* Progressive, castrate-resistant, metastatic adenocarcinoma of the prostate
* Eastern Cooperative Oncology Group (ECOG) less than or equal to 2
Design:
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Male
- Target Recruitment
- 21
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description TRC105 10 mg/kg every 2 weeks TRC105 Intravenous infusion at 10 mg/kg every 2 weeks TRC105 20 mg/kg every 2 weeks TRC105 Intravenous infusion at 20 mg/kg every 2 weeks TRC105 1 mg/kg every 2 weeks TRC105 Intravenous infusion at 1 mg/kg every 2 weeks TRC105 15 mg/kg every 2 weeks TRC105 Intravenous infusion at 15 mg/kg every 2 weeks TRC105 3 mg/kg every 2 weeks TRC105 Intravenous infusion at 3 mg/kg every 2 weeks TRC105 10 mg/kg weekly TRC105 Intravenous infusion at 10 mg/kg weekly
- Primary Outcome Measures
Name Time Method Phase I: Maximum Tolerated Dose (MTD) of TRC105 Given Every Two Weeks. 6 months The MTD, to be administered in the phase II portion, is defined as the highest dose studied for which the incidence of dose limiting toxicity (DLT) was less than 33%. TRC105 was administered at 20 mg/kg intravenous every two weeks until MTD was achieved.
- Secondary Outcome Measures
Name Time Method Number of Participants With Adverse Events Date treatment consent signed to date off study, approximately 43 months, 5 days Here is the number of participants with adverse events. For a detailed list of adverse events, see the adverse event module.
Dose Limiting Toxicity (DLT) First 28 days on study Dose limiting toxicity is defined as any grade 3 or higher hematologic (excluding anemia) or non-hematologic toxicity considered to be possibly related to TRC105.
Prostatic-Specific Antigen (PSA) Decline 1- week intervals up to 6 months PSA decline (i.e., PSA greater than 4.0 ng/mL) is defined as two consecutively rising PSA values at a minimum of 1-week intervals (2.0 ng/mL is the minimum starting values for PSA). Normal PSA is 4.0 ng/mL or lower.
Clinical Response 56 days (one cycle = 28 days, restaging post cycle 2) Clinical response was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST). Complete response (CR) is disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. Partial response (PR) is at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. Progressive disease (PD) is at least a 20% decrease in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). Stable disease (SD) is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.
Trial Locations
- Locations (1)
National Institutes of Health Clinical Center, 9000 Rockville Pike
🇺🇸Bethesda, Maryland, United States