A Phase II Trial of Enzalutamide in Combination With PSA-TRICOM in Patients With Non-Metastatic Castration Sensitive Prostate Cancer
- Androgen deprivation therapy (ADT) and surveillance are standard therapy options for
prostate cancer patients with biochemical progression after localized therapy (or
nonmetastatic castration sensitive prostate cancer; nmCSPC also known as D0 Prostate
Cancer). These patients cannot be cured of prostate cancer and the primary therapeutic
goal is to contain the disease with anti-androgen therapy.
- ADT can be administered intermittently consisting of multiple short courses or
continuously with similar long-term clinical outcomes.
- Previous studies with high dose bicalutamide (androgen receptor antagonist, ARA) have
shown significant biochemical control in nmCSPC.
- Enzalutamide is a modern ARA with greater androgen receptor affinity than bicalutamide
and further impairs downstream effects of androgen receptor activation. This agent is
FDA approved for the treatment of chemotherapy refractory metastatic castration
resistant prostate cancer.
- Given its favorable side effect profile, there is strong interest in using enzalutamide
to treat patients with earlier stages of prostate cancer including nmCSPC.
- PSA-TRICOM (Prostvac(Trademark); developed by the National Cancer Institute [NCI] and
licensed to BN Immunotherapeutics, Mountain View, CA) is a novel candidate prostate
cancer immunotherapy for the treatment of prostate cancer. It is a viral vector based
therapeutic cancer vaccine that is administered via subcutaneous injections. In a
randomized controlled Phase 2 trial, PSA-TRICOM therapy was associated with a
prolongation of survival in men with metastatic castrate-resistant prostate cancer. A
phase III trial is currently enrolling patients in this same population.
- There is also rationale to use therapeutic cancer vaccines such as PSA-TRICOM in
earlier stage prostate cancer patients to maximize the potential therapeutic effect of
immune stimulating therapy.
- An ongoing NCI clinical trial that combined PSA-TRICOM with flutamide (an older FDA
approved ARA) in nonmetastatic castration resistant prostate cancer has demonstrated
safety and suggested the potential to improve time to progression.
- Analysis of previous trials using therapeutic cancer vaccines alone and in combination
suggests that such therapies may alter tumor growth rate. If this hypothesis is
correct, a therapeutic cancer vaccine may alter tumor regrowth rate/recovery after a
cytoreductive therapy such as enzalutamide is discontinued.
- If PSA-TRICOM with enzalutamide can result in a reduced tumor regrowth rate as measured
by PSA after a short course of enzalutamide therapy, it would provide an important
proof of concept and potentially define it more clear role for therapeutic cancer
vaccines in prostate cancer and potentially other cancers.
- To prospectively evaluate this hypothesis, all patients will be treated with
enzalutamidein a manner similar to how short course ADT is used in common clinical
practice. Half the patients will also be given PSA-TRICOM and PSA recovery after
enzalutamide therapy will be compared between patients who received vaccine and those
who did not.
-Determine if PSA-TRICOM combined with the novel androgen receptor antagonist enzalutamide
will result in a decrease in PSA growth kinestics (tumor re-growth rate) after enzalutamide
discontinuation in patients with non-metastatic, castration sensitive prostate cancer (i.e.
patients with normal testosterone).
- Patients with nonmetastatic castration sensitive prostate cancer and a PSA over 2.0
- Patients with normal testosterone levels.
- Histologically confirmed adenocarcinoma.
- Patients with a PSA doubling time of 12 months or less.
- ECOG 0-1.
- Randomized pilot study
- Thirty-four patients to be enrolled and randomized 1:1 to
- Arm A: Enzalutamide for 3 months.
- Arm B: Enzalutamide 3 months + PSA-TRICOM on weeks 1, 3,5,9,13,17 and 21.
-Patient Population: Biochemical Recurrence or Rising PSA after surgery or RT with normal
testosterone (nmCSPC). RANDOMIZE:
- Arm A: Enzalutamide (n=17)
- Arm B: Enzalutamide + PSA-TRICOM (n=17)
Enzalutamide will be given at the standard dose of 160 mg daily for 3 months. PSA-TRICOM
(Prostvac-V/F) will consist of a single subcutaneous (sc) immunization of Prostvac-V or
placebo in Week 1, followed by 6 Prostvac-F immunizations administered in Weeks 3, 5, 9,13,
17, and 21. Patients will be followed for PSA recovery after enzalutamide has been
discontinued. Patients who do not develop a 25% decline in PSA after 3 months will not be
evaluated for tumor re-growth and additional patients will be enrolled to evaluate for that
endpoint. Patients will be stratified based a doubling time of greater than or less than 6
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Decrease in tumor re-growth rate
Ravi A Madan, M.D.
National Cancer Institute (NCI)
United States: Federal Government
|National Institutes of Health Clinical Center, 9000 Rockville Pike||Bethesda, Maryland 20892|