Inhibiting Tumor Angiogenesis in Metastatic Hormone-Refractory Prostate Cancer
Name of the Trial
Phase I/II Study of TRC105 in Metastatic Castrate Resistant Prostate Cancer (NCI-10-C-0062). See the protocol summary.
Dr. William Dahut, NCI Center for Cancer Research
Why This Trial Is Important
Prostate cancer is the most frequently diagnosed non-skin malignancy and second leading cause of cancer death among American men. Most prostate tumors initially depend on androgens, which are male sex hormones, to continue growing. To combat these growth-promoting effects, antiandrogen therapies, which lower the concentrations of male hormones in the blood to “castrate” levels, are administered after surgery or radiation therapy. Even in the presence of reduced hormone levels, though, some tumors will eventually start to grow again and are referred to as hormone refractory or castration resistant. Few treatments are available for castration-resistant prostate cancer (CRPC). However, the current standard of care for metastatic CRPC is a combination of the chemotherapy drug docetaxel and the steroid prednisone.
All solid tumors require an adequate blood supply for continued growth. Inhibiting the formation of new blood vessels, or angiogenesis, is a cancer treatment method that has shown promise in many types of advanced cancer and is under investigation as a treatment for prostate cancer. A previous clinical trial demonstrated that combining docetaxel with the antiangiogenic agent bevacizumab (Avastin), which targets a blood vessel growth factor, was well-tolerated and resulted in a substantial decrease in levels of prostate specific antigen (PSA), a marker for tumor progression, in the majority of patients. However, this regimen did not improve survival; thus researchers continue to search for new drugs that target tumor-associated blood vessels more specifically.
In this study, which is being conducted at the NIH Clinical Center, researchers will test whether treatment with a novel monoclonal antibody, TRC105, that targets a protein highly expressed on the surface of tumor blood vessels improves the outcome of men with metastatic CRPC. Men who are at least 18 years of age and have been diagnosed with progressive, castration-resistant adenocarcinoma of the prostate are eligible to enroll. The first phase of the trial will involve a dose escalation (increase) study to establish the maximum tolerated dose. The second phase will examine progression-free survival in patients with disease progression after treatment with docetaxel and no prior antiangiogenic therapy.
“Currently, there is no curative therapy for metastatic castration-resistant prostate cancer,” said Dr. Dahut. “TRC105 is an experimental drug that has been demonstrated to block angiogenesis and has a very different target than previously studied antiangiogenic anticancer agents. However, it has not been validated to treat prostate cancer in general or castration-resistant prostate cancer in particular.
“If the regimen proves safe and effective, we hope that it will offer a clinically important option for men with metastatic castration-resistant prostate cancer,” he added.