The USC Norris Comprehensive Cancer Center has recently begun recruiting female participants for three new clinical trials studying breast, ovarian and cervical cancer immunotherapies. It is scheduled to open recruitment for a second ovarian cancer study over the summer. No other facility in California provides patients with access to all four of the trials.
“Research on cancer immunotherapy has proliferated over the years, but we are just beginning to see that research move into the clinic — these clinical trials are all new patient treatments that are targeted to boost the immune system,” said oncologist Agustin Garcia, M.D., associate professor of clinical medicine at the Keck School of Medicine of USC and principal investigator on two of the studies.
The first is a multi-center, phase three trial for newly diagnosed breast cancer, which means the treatment has been deemed safe and effective in previous studies but must be observed in a larger group to confirm the findings. About 25 percent of people with lymph node-positive breast cancer who receive the most effective available treatments available will still have a recurrence within three years after achieving remission. In the “PRESENT” trial, sponsored by Galena Biopharma, Inc., Garcia is testing the efficacy of the nelipepimut-S vaccine to prevent or delay breast cancer recurrence after receiving conventional chemotherapy. The drug, marketed as NeuVax, stimulates the body’s immune response to recognize, neutralize and destroy cancer cells that express the HER2 protein, a common target for breast tumor medicine.
Patients who express high levels of the HER2 protein are typically treated with trastuzumab, also known as Herceptin. However, about 20 percent of women with breast cancer express lower levels of HER2 and are not eligible to take trastuzumab. If NeuVax works, the vaccine could help those women.
“The traditional concept was that the immune system could not recognize tumors,” Garcia said. “Now, we see that the immune system just doesn’t react enough. That’s why vaccines like NeuVax are trying to make the immune system stronger.”
Similarly, the “CANVAS” trial is a phase three study of whether the Cvac vaccine can help prevent epithelial ovarian cancer from recurring. While most patients achieve complete remission after surgery and chemotherapy, many will relapse and need chemotherapy again.)
Adding Cvac to the front-line treatment regimen for ovarian cancer patients could potentially delay or prevent ovarian cancer from relapsing and potentially lengthen overall survival. It is created from special cells taken from the ovarian cancer patient’s blood and “trained” in the lab to destroy certain tumor cells when re-introduced into the body. CANVAS is a global multi-center study sponsored by Prima BioMed Ltd., for newly diagnosed patients with ovarian cancer. The trial’s principal investigator at USC is Huyen Pham, M.D., assistant professor of clinical obstetrics and gynecology at the Keck School of Medicine of USC. It is slated to begin recruiting USC patients this summer.
Garcia is leading another study of ovarian cancer patients, a multi-center phase two trial studying whether the drug INCB024360 can help patients whose ovarian cancer comes back after successful first-line treatment. In some women, the only evidence of recurrence is an abnormal blood test (a tumor marker known as CA-125), meaning that they show no symptoms and their physical exam and imaging studies are all normal. The patient must decide whether to undergo chemotherapy and its side effects when she is feeling otherwise healthy or wait until other symptoms appear and the cancer has advanced. INCB024360 is being studied as a less toxic alternative to chemotherapy.
Experimental drugs in phase two clinical trials have been shown to be generally safe with minimal side effects and are being studied for effectiveness. INCB024360 inhibits tryptophan, an enzyme that dampens the body’s immune response against cancer cells. Preclinical studies have shown that inhibition of tryptophan increases the immune system’s tumor-killing activity as well as the effectiveness of various chemotherapy drugs. The trial, supported by Incyte Corp., is randomized, which means that some participants will receive INCB024360 and others will receive tamoxifen, a hormone-based treatment that is effective for some women with recurrent ovarian cancer.
The fourth trial, led by Yvonne Lin, M.D., assistant professor of obstetrics and gynecology at the Keck School of Medicine, is a multi-center phase one cervical cancer study developed at USC and sponsored by the National Cancer Institute’s Gynecologic Oncology Group and the USC Norris Auxiliary. Chemoradiation usually cures locally advanced cervical cancer except for a critical subset of high-risk patients with tumors that may have spread to the lymph nodes. Lin’s trial is focused on finding a new treatment option for those women.
Since most cervical cancers are caused by the human papillomavirus (HPV) infecting cervical cells, Lin and her colleagues believe the body’s own immune system can eliminate those HPV-infected cells with the help of a new drug called ipilimumab. The immune system normally works by starting and stopping like a car controlled by gas and brake pedals. Marketed as Yervoy and approved by the Food and Drug Administration in 2011 to treat melanoma, ipilimumab essentially works by temporarily taking off the brakes so that the immune system can continue running — and killing off HPV-infected tumor cells.
Because it is a phase one study, the trial’s main goals are to identify side effects and select the best dose of the drug to give to these high-risk patients after chemoradiation.
“This type of immune modulatory treatment is very new,” said Lin. “No one really knows the kinetics of the immune system — how long it takes to rev up and rev down. So, an important part of our trial will actually try to answer that question by taking three snapshots of the patient’s immune landscape: at diagnosis, after chemoradiation and over the course of treatment with ipilimumab.”
Patients interested in learning more about the clinical trials at the USC Norris Comprehensive Cancer Center can contact the Clinical Investigation Support Office at (323) 865-0541 or firstname.lastname@example.org, or visit http://uscnorriscancer.usc.edu/ClTrials/.
• Efficacy and Safety Study of NeuVax (Nelipepimut-S or E75) Vaccine to Prevent Breast Cancer Recurrence (PRESENT). Sponsored by Galena Biopharma, Inc. ClinicalTrials.gov Identifier, NCT01479244.
• Cvac as Maintenance Treatment in Patients With EOC in Complete Remission Following First-Line Chemotherapy (CANVAS). Sponsored by Prima BioMed Ltd. ClinicalTrials.gov Identifier, NCT01521143.
• A Phase 2 Study of the IDO Inhibitor INCB024360 Versus Tamoxifen for Subjects With Biochemical-recurrent-only EOC, PPC or FTC Following Complete Remission With First-line Chemotherapy. Sponsored by Incyte Corp. ClinicalTrials.gov Identifier, NCT01685255.
• Chemoradiation Therapy and Ipilimumab in Treating Patients With Locally Advanced Cervical Cancer. Sponsored by National Cancer Institute (GOG9929) and USC Norris Auxiliary. ClinicalTrials.gov Identifier, NCT01711515.
ABOUT USC NORRIS COMPREHENSIVE CANCER CENTER
USC Norris Comprehensive Cancer Center has been leading the fight to make cancer a disease of the past. As one of the eight original comprehensive cancer centers in the United States, our mission is to treat and prevent cancer by advancing and integrating education, research, and personalized patient care. For 40 years, we have been revolutionizing cancer research with innovative surgical techniques and novel cancer treatments. Our breakthroughs and discoveries in the field of epigenetics have led the way to a greater understanding of the underlying causes of cancer and new methods of prevention, detection, and treatment. With a multidisciplinary team of over 250 dedicated scientists and physicians, we offer patients hope in the battle against cancer.
Contact: Alison Trinidad at (323) 442-3941
Interviews available in Spanish by request.