CARAVAN: Checkpoint-Radiation-Vaccine Neoadjuvant Trial for Metastatic Prostate Cancer
About CARAVAN: Checkpoint-Radiation-Vaccine Neoadjuvant Trial for Metastatic Prostate Cancer
- Radiation therapy (RT) or radical prostatectomy are the primary treatment strategies for men diagnosed with locally advanced prostate cancer. However, even with the addition of androgen deprivation (ADT) therapy, many patients experience recurrences and progress to lethal disease. Other therapeutic strategies are needed to extend the lives of these patients. .
- Drs. Dicker, Fong and team are investigating whether the addition of neoadjuvant immunotherapy regimens to RT will improve patient outcomes.
- A Phase I clinical trial (CARAVAN) will be initiated to test the addition of a combination of immunotherapies to RT prior to radical prostatectomy in prostate cancer patients with locally advanced disease. The immunotherapy combination consists of intratumoral injection of Pembrolizumab and Ipilimumab, and infusional administration of ADXS-PSA, a prostate cancer vaccine that activates immune responses against the PSA protein that is expressed by prostate cancer cells.
- Once the maximum tolerated immunotherapy combination with RT has been determined, a Phase II clinical trial will be initiated to test the efficacy of that regimen in men with oligometastatic prostate cancer (early metastatic prostate cancer where 5 or less metastatic lesions are present). Immune responses induced by this therapeutic combination will be assessed by comparing immune populations and the T cell repertoire present in blood and tumor specimens before vs. after treatment.
- Exosomes are microvesicles that are shed from various cell types including tumor and immune cells and contain proteins, DNA, and RNA. The molecular components of tumor and immune cell-secreted exosomes obtained from patient peripheral blood will be assessed to determine if they can serve as biomarkers of immune responses and/or clinical outcomes.
What this means for patients: Immunotherapy may hold the potential to cure men with locally advanced prostate cancer and may synergize with radiation therapy (RT). Drs. Dicker, Fong and team are testing whether the addition of a combination immunotherapy regimen to neoadjuvant RT prior to radical prostatectomy will improve patient outcomes. If successful, this project will lead to a new therapeutic strategy for treating prostate cancer as well as biomarkers to identify men who should receive this treatment.
Adam Dicker, MD, PhD (Thomas Jefferson University) & Lawrence Fong, MD (University of California – San Francisco)
James Hodge, PhD, MBA (National Cancer Institute), Leonard Gomella, MD (Thomas Jefferson University), Jonathan Mann, MD (Thomas Jefferson University), Jean Hoffman-Censits, MD (Thomas Jefferson University), Albert Chang, MD, PhD (University of California – San Francisco), W. Kevin Kelly, DO (Thomas Jefferson University), Benjamin Leiby, PhD (Thomas Jefferson University), Nicola Mason, DVM, PhD (University of Pennsylvania), Ulrich Rodeck, MD, PhD (Thomas Jefferson University), Ruth Birbe, MD (Thomas Jefferson University)