A Randomized Phase II Trial Combining Vaccine Therapy With PROSTVAC/TRICOM and Flutamide vs. Flutamide Alone in Men With Androgen Insensitive, Non-Metastatic (D0.5) Prostate Cancer
Protocol # 07-C-0107, NCT00450463
- Why is this trial important?
- Who is eligible for this trial?
- What types of drugs or therapies are being used?
- What is the study outline?
- What is the frequency and duration of the visits?
- What are the costs?
- Who is the Principal Investigator?
- Where is this trial taking place?
- Who are the contacts for this trial?
- Where can additional information be found?
Adenocarcinoma of the prostate is the most common cancer diagnosis in American men and the second leading cause of cancer death. Many men receiving hormonal therapy for prostate cancer develop a rising PSA but have no evidence of disease on bone scan or CT scan. Currently, there is no standard of care for these patients. In a prior clinical study, we showed preliminary clinical data that combining hormone therapy with a vaccine targeting PSA may benefit patients with this stage prostate cancer. In our current trial, patients will be randomized to receive either flutamide alone (an FDA-approved pill that is active in prostate cancer) or in combination with a prostate cancer vaccine to determine if the addition of the vaccine can improve the outcome (prolong disease progression) compared with flutamide alone. The study will also seek to understand the immunologic effects of these treatments.
Who is eligible for this trial? (PDQ)
- Histopathological documentation of prostate cancer confirmed in the NIH Laboratory of Pathology
- Must have non-metastatic castration-resistant prostate cancer:
- Rising PSA with castrate levels of testosterone and no evidence of metastatic disease on CT scan or bone scan (rising PSA is defined as two consecutively rising PSA levels, separated by ≥ 1 month apart, with the last measurement > 1 ng/mL)
- Patients must recover from prior therapy and show evidence of rising PSA
- No history of a rising PSA on flutamide
- Patients who have received prior flutamide therapy for > 1 month (prior to enrolling on study) are not eligible
- Life expectancy ≥ 6 months
- ECOG performance status of 0–1
- Granulocyte count ≥ 1,500/mm3; platelet count ≥ 100,000/mm3; hemoglobin ≥ 9 g/dL; lymphocyte count ≥ 500/mm3; bilirubin < 1.5 mg/dl; AST and ALT < 2.5 x upper limit of normal (ULN)
- Patients must have < grade 2 proteinuria (unless the cause is determined not to be renal)
- Creatinine clearance ≥ 60 mL/min with 24-hour urine collection
- HIV negative, hepatitis B and C negative
- No other active malignancies within the past 3 years (with the exception of non-melanoma skin cancers or carcinoma in situ of the bladder) or life-threatening illnesses
- Recovered from all prior therapy
- No autoimmune diseases
- No serious intercurrent medical illness that would preclude study participation
- No history of heart disease; no history of pulmonary disease
- No CNS involvement or history of seizures, encephalitis, or multiple sclerosis
- Patients with prior splenectomy are not eligible
- No hypersensitivity to egg products
- Flutamide is an FDA-approved anti-androgen pill that blocks the effects of testosterone on the androgen receptor of the prostate cancer cell and may slow the progression of prostate cancer
- PROSTVAC-TRICOM vaccines consist of two types, both containing PSA protein and other proteins that help increase the vaccines stimulation of the immune response to PSA found on prostate cancer cells
- PROSTVAC_V/TRICOM is a modified vaccinia virus. Vaccinia is the same virus that has been used for many years to vaccinate against smallpox. This is the “priming” vaccine and is only given once
- PROSTVAC-F/TRICOM, the second vaccine, is a virus similar to the vaccinia virus and is called fowlpox virus. This is a booster vaccine given 4 weeks after the priming vaccine
- GMCSF, also called sargramostim, is a commercially approved drug used to stimulate the immune system
What is the study outline? (PDQ)
Patients will be randomized on a 1:1 basis to Arm I (flutamide alone) or Arm II (flutamide + vaccine).
- Patients receive flutamide 250 mg orally 3 x daily (TID) beginning on Day 1
- Flutamide 250 mg orally TID beginning on Day 1
- PROSTVAC-V/TRICOM (vaccinia) subcutaneously on Day 1 of the first cycle only
- Followed by monthly (every 4 weeks) boosting vaccinations with PROSTVAC-F/TRICOM (fowlpox) subcutaneously on Day 1 of each cycle
- Sargramostim 100 mcg subcutaneously will be given at the vaccine site for 4 consecutive days starting on Day 1 of each vaccine cycle
- Treatment repeats every 28 days
After 3 months of therapy, patients receiving the flutamide alone (Arm I) may cross over to receive vaccine if they develop a rising PSA and scans are without metastatic disease.
At the initial screening visit, participants may need to stay in Bethesda for up to 2 days for eligibility and medical evaluation. After start of study, participants will return every 4 weeks for medical evaluation (outpatient visit).
There is no charge for medical care received at the National Institutes of Health (NIH) Clinical Center. Patients will be responsible for travel costs for their initial screening visits. In most cases, once patients are enrolled in a trial, the National Cancer Institute (NCI) will pay the transportation costs for all subsequent trial-related visits for patients who do not live in the local area. In addition, these patients will receive a small per diem to help offset the costs of meals and lodging if they are being treated as outpatients.
It will be important to maintain your current insurance plan to cover all medical care that is provided away from the NIH Clinical Center.
No U.S. citizen or permanent U.S. resident residing in the U.S. who otherwise meets the eligibility requirements will be denied enrollment in clinical research protocols because of their inability to pay the costs of travel and subsistence.
Dr. Madan is an assistant clinical investigator at the National Cancer Institute (NCI), conducting clinical research in therapeutic cancer vaccines and genitourinary malignancies. Dr. Madan received his M.D., from the UMDNJ–New Jersey Medical School in 2001 and completed his internal medicine residency at UMDNJ–University Hospital in June 2004. He joined the NCI Medical Oncology Branch as an oncology/ hematology fellow in 2005. He currently holds a joint appointment in the Medical Oncology Branch and the Laboratory of Tumor Immunology and Biology. His research interests are focused on immune stimulating therapeutic cancer vaccines and novel therapies in the treatment of prostate cancer.
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