Prostvac in Patients With Biochemically Recurrent Prostate Cancer

BACKGROUND

- Androgen deprivation therapy (ADT) and surveillance are treatment options for prostate
cancer patients with biochemical progression after localized therapy (biochemically
recurrent prostate cancer). The primary goal in these patients is to prevent morbidity
from their cancer and to do so with limited toxicity.

- Prostvac (Prostvac ; 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, Prostvac therapy was associated with a prolongation
of survival in men with metastatic castrate-resistant prostate cancer. A phase III trial
recently completed accrual of patients in this same population.

- There is also rationale to use therapeutic cancer vaccines such as Prostvac in earlier
stage prostate cancer patients to maximize the potential therapeutic effect of immune
stimulating therapy.

- Analysis of previous trials using therapeutic cancer vaccines alone suggests that such
therapies may alter tumor growth rate.

OBJECTIVE

Primary Objective:

-Determine if the therapeutic cancer vaccine prostvac can decrease tumor growth rate as
measured by PSA rise after 6 months compared to a group getting surveillance alone.

KEY ELIGIBILITY CRITERIA

- Histologically confirmed adenocarcinoma of the prostate

- Patients with negative CT Scan and Tc-99m Bone Scan

- Patients with a PSA over 0.8 ng/ml for patients following radical prostatectomy or for
patients following definitive radiation therapy: a rise in PSA of greater than or equal
to 2 ng/mL above the nadir

- Patients with a PSA doubling time of 5-15 months

- No history of active autoimmune disease or history of organ compromising autoimmune
disease

- ECOG 0-1

DESIGN

- Randomized study

- Accrual goal is 36 evaluable patients per arm; randomized 1:1 to:

- Arm A: Prostvac for 6 months with an additional optional year of maintenance for
eligible patients OR

- Arm B: Surveillance for 6 months, then Prostvac for 6 months with an additional
year of maintenance for eligible patients

- INCLUSION CRITERIA:

- Histopathological documentation of prostate cancer confirmed in either the Laboratory
of Pathology at the National Institutes of Health (NIH) Clinical Center, Walter Reed
National Military Medical Center, MSKCC, DFCI or BIDMC prior to enrollment. If no
pathologic specimen is available, patients may enroll with a pathologist s report
showing a histologic diagnosis of prostate cancer and a clinical course consistent
with the disease.

- Biochemical progression after definitive radiation or surgery defined as follows:

- For patients following definitive therapy: a rise in PSA of greater than or equal
to 2ng/mL above the nadir (per RTOG-ASTRO consensus criteria).

- For patients following radical prostatectomy: rising PSA after surgical
procedure. (Patients must have a PSA greater than or equal to 0.8 ng/ml)

- ECOG performance status of 0 1 (Karnofsky greater than or equal to 80%).

- Patients must have a PSA doubling time of 5-15 months.

- Patients must have a rising PSA as confirmed by 3 values done at least 1 week apart
and over no less than 1 month.

- Recovery from acute toxicity related to prior therapy, including surgery and
radiation, or no toxicity greater than or equal to grade 2.

- Negative CT scan/MRI and bone scan for metastatic prostate cancer.

- Hematological eligibility parameters (within 16 days before starting therapy)

- Granulocyte count greater than or equal to 1000/mm3

- Platelet count greater than or equal to 100 000/mm3

- Hgb greater than or equal to 10g/dL

- Biochemical eligibility parameters (within 16 days before starting therapy):

--Hepatic function: bilirubin less than or equal to 1.5mg/dL (OR in patients with
Gilbert s syndrome normal.

- No other active malignancies within the past 36 months (with the exception of
nonmelanoma skin cancers or carcinoma in situ of the bladder) or life-threatening
illnesses, in the opinion of the investigator

- Willing to travel to the NIH, MSKCC, DFCI, BIDMC for follow-up visits.

- 18 years of age or older.

- Able to understand and sign informed consent.

- Baseline testosterone greater than or equal to 100 ng/dl

- PSA less than or equal to 30 ng/mL.

- The effects PROSTVAC on the developing human fetus are unknown. For this reason, men
must agree to use adequate contraception (hormonal or barrier method of birth control;
abstinence) prior to study entry, for the duration of study therapy and at least one
month post therapy. Should a woman become pregnant or suspect she is pregnant while
her partner is participating in this study, she should inform her treating physician
immediately.

EXCLUSION CRITERIA:

- Immunocompromised status due to:

- Human immunodeficiency virus (HIV) positivity.

- Active autoimmune diseases such as Addison's disease, Hashimoto's thyroiditis,
systemic lupus erythematosus, Sjogren syndrome, scleroderma, myasthenia gravis,
Goodpasture syndrome or active Grave's disease. Patients with a history of
autoimmunity that has not required systemic immunosuppressive therapy or does not
threaten vital organ function including CNS, heart, lungs, kidneys, skin, and GI
tract will be allowed.

- Other immunodeficiency diseases

- Splenectomy

- Chronic administration (defined as daily or every other day for continued use > 14
days) of corticosteroids deemed systemic by investigator within 28 days before the
first planned dose of PROSTVAC. Use of inhaled steroids, nasal sprays, intra-articular

injections and topical creams for small body areas is allowed.

- Serious intercurrent medical illness that, in the judgment of the investigator, would
interfere with patient s ability to carry out the treatment program.

- Other medications used for urinary symptoms including 5-alpha reductase inhibitors
(finasteride and dutasteride) and alternative medications known to alter PSA (eg
phytoestrogens and saw palmetto)

- History of prior chemotherapy

- History of prior immunotherapy within the last 3 years

- Major surgery within 4 weeks prior to enrollment (Day 1 visit).

- History of allergic reactions attributed to compounds of similar chemical or biologic
composition to poxviral vaccines (e.g., vaccinia vaccine)

- Known allergy to eggs, egg products, aminoglycoside antibiotics (for example,
gentamicin or tobramycin).

- History of atopic dermatitis or active skin condition (acute, chronic, exfoliative)
that disrupts the epidermis

- Previous serious adverse reactions to smallpox vaccination

- Unable to avoid close contact or household contact with the following high-risk
individuals for three weeks after the Day 1 vaccination: Day 1 vaccination: (a)
children less than or equal to 3 years of age, (b) pregnant or nursing women, (c)
individuals with current or extensive eczema or other eczemoid skin disorders, or (d)
immunocompromised individuals, such as those with HIV.

- Receipt of an investigational agent within 28 days (or 56 days for an antibody-based
therapy) before the first planned dose of study drugs.

- Patients who test positive for HBV or HCV

- Uncontrolled hypertension (SBP>170/ DBP>105)

- Recruitment Strategies

This study will be listed on available websites (www.clinicaltrials.gov,

https://ccr.cancer.gov/clinical-trials-search-start) and participants will be recruited
from the

current patient population at NIH.