RPCI enrolls patients in clinical trials of immunotherapy approaches for treating genitourinary cancers

Researchers at the Roswell Park Cancer Institute (RPCI) Center for Immunotherapy are enrolling patients in three different clinical trials of novel immunotherapy approaches for treating genitourinary cancers. One of the studies will assess how patients' immune systems respond to targeted radiation treatments for metastatic kidney cancer. Another will evaluate how patients' immune systems respond to targeted radiation treatments for metastatic prostate cancer, in combination with immunotherapy, and a third will focus on a new type of immunotherapy for bladder cancer.

"The results of our work in the laboratory were so exciting that we have moved these studies into the clinic for treating patients," said Thomas Schwaab, MD, PhD, assistant professor in the departments of Urology and Immunology at RPCI, who is leading the two investigator-initiated clinical trials.

Study NCT01892930 — Radiation therapy/immunotherapy in kidney cancer

The first clinical trial, which will enroll 10 to 15 patients, is a phase I trial evaluating the safety of using stereotactic body radiation therapy (SBRT) to treat kidney tumors before removing them surgically. SBRT, which is FDA-approved for the treatment of other types of cancer, targets the tumor with great precision while avoiding damage to normal tissue nearby.

The study is believed to be the first clinical trial to assess the impact of enhancing the immune system with immunotherapy before standard treatment. Immunotherapy is the only treatment modality that has been shown to be curative against metastatic kidney cancer.

The trial is open to patients with metastatic kidney cancer who do not have any conditions that would make them ineligible for surgery. Patients will undergo SBRT on day 1, followed by either partial or total removal of the kidney (nephrectomy) on day 29.

"Unfortunately, patients with metastatic kidney cancer have very poor prospects for survival," Dr. Schwaab said. "This is the first study ever to use radiation to treat kidney cancer. We hope that delivering radiation to the tumor site will not only destroy the tumors directly but also 'wake up' the immune system so it will be able to fight the cancer wherever it has spread in the body."

More information about the study, titled "Immunologic Impact of Stereotactic Body Radiation Therapy in Patients with Metastatic Renal Cell Carcinoma," can be found at http://clinicaltrials.gov/show/NCT01892930.

Study NCT01833208 — Combination radiotherapy/immunotherapy in prostate cancer

Dr. Schwaab is also leading a phase I clinical trial to help determine whether radiation therapy can boost the immune-system response generated by sipuleucel-T (Provenge), the first FDA-approved therapeutic cancer vaccine, used for the treatment of metastatic prostate cancer.

"We will look at the effectiveness of combining radiation therapy and immunotherapy for treating prostate cancer," Dr. Schwaab said. "Sipuleucel-T has shown a modest benefit for patients with metastatic prostate cancer, extending survival by an average of four months. We hope radiation will provide an additional boost to the immune system for an even greater survival benefit for patients with metastatic prostate cancer."

The trial is open to patients from either RPCI or Western New York Urology Associates LLC whose prostate cancer has returned after anti-hormone therapy, whose disease has spread to the bone, and who have been prescribed sipuleucel-T but have not yet started treatment. Researchers plan to enroll 15 patients. Two days after the first sipuleucel-T treatment, patients will undergo a single dose of radiation therapy to at least one bone lesion.

More information about the study, titled "Pilot: Impact of High-Dose Single-Fraction Radiation on Immunogenicity of Sipuleucel-T in Metastatic Castration-Recurrent Prostate Cancer Patients," can be found at http://clinicaltrials.gov/ct2/show/NCT01833208.

Study NCT01353222 — Adjuvant immunotherapy in bladder cancer

The third study, sponsored by the biotechnology company Dendreon Corp., will enroll 180 patients treated at 58 different centers, including Roswell Park. It is a phase II study evaluating DN24-02 given in addition to another type of treatment. Used in treating high-risk, HER2-positive urothelial carcinoma, DN24-02 is an immunotherapy that uses the patient's own antigen-presenting immune cells — the same strategy associated with sipuleucel-T, an immunotherapy used to treat metastatic prostate cancer. Patients will be informed whether or not they are being given the treatment under study.

Patients who have had their bladder removed and those who have had their kidney and ureter removed and who are either not eligible for or decline chemotherapy ("standard of care") may be eligible to participate in this trial. Dr. Schwaab emphasized that patients should be enrolled in the trial soon after surgery. Patients will be randomly assigned to treatment with DN24-02 or best supportive care. Researchers will compare results of patients who receive best supportive care vs. those who receive DN24-02, and will evaluate the drug's safety, assess how the immune system reacts and determine whether the drug delays recurrence of urothelial cancer.

"The patients we are recruiting for this study are at high risk for cancer recurrence," Dr. Schwaab said. "This study gives them the option of being treated with an approach that has shown very promising results in prostate cancer."