A Phase I/II Study of TRC105 in Metastatic Castrate Resistant Prostate Cancer (CRPC)
- 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
- 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
- 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:
1. Chemotherapy-na ve for metastatic disease (no prior antiangiogenic therapy)
2. 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.
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
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%.
6 month progression - free survival
William L Dahut, M.D.
National Cancer Institute (NCI)
United States: Federal Government
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