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A Randomized Phase II Study of Either Immunotherapy With a Regimen of Recombinant Pox Viruses That Express PSA/B7.1 Plus Adjuvant GM-CSF and IL2 or Hormone Therapy With Nilutamide in Patients With Hormone Refractory Prostate Cancer and No Radiographic Evidence of Disease


Phase 2
18 Years
N/A
Not Enrolling
Male
Prostate Cancer

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Trial Information

A Randomized Phase II Study of Either Immunotherapy With a Regimen of Recombinant Pox Viruses That Express PSA/B7.1 Plus Adjuvant GM-CSF and IL2 or Hormone Therapy With Nilutamide in Patients With Hormone Refractory Prostate Cancer and No Radiographic Evidence of Disease


OBJECTIVES:

- Compare the difference in time to radiographic evidence of disease progression at 6
months in patients with hormone-refractory prostate cancer when treated with vaccine
containing recombinant vaccinia-prostate-specific antigen (PSA) admixed with rV-B7.1
plus recombinant fowlpox-PSA vaccine, sargramostim (GM-CSF), and interleukin-2 vs
nilutamide alone.

- Evaluate the vaccination therapy in relation to the change in T-cell precursor
frequency and to the rise of serum PSA in this patient population.

OUTLINE: This is a randomized study. Patients are stratified according to HLA-A2 typing
(positive vs negative). Patients are randomized to one of two treatment arms.

- Arm I: Patients receive vaccine containing recombinant vaccinia-prostate-specific
antigen (PSA) and rV-B7.1 subcutaneously (SC) on day 2 only. Beginning on day 30,
patients receive recombinant fowlpox-PSA vaccine SC every 4 weeks for 12 vaccinations
and then every 12 weeks thereafter. Patients also receive sargramostim (GM-CSF) SC
daily on days 1-4 and interleukin-2 SC daily on days 8-12 with each vaccination.

Patients without disease progression after 12 courses receive the vaccine regimen every 12
weeks.

- Arm II: Patients receive oral nilutamide daily. Treatment continues in both arms for at
least 6 months in the absence of disease progression or unacceptable toxicity.

After 6 months of therapy, patients with a rising PSA and no radiographic evidence of
disease progression may receive therapy in the other arm in addition to the therapy to which
they were randomized.

Patients are followed monthly for 6 months and then every 2 months thereafter.

PROJECTED ACCRUAL: A total of 56-78 patients (28-39 per treatment arm) will be accrued for
this study within 1.5-2 years.

Inclusion Criteria


DISEASE CHARACTERISTICS:

- Histologically confirmed hormone-refractory adenocarcinoma of the prostate

- Rising PSA after orchiectomy and/or while receiving at least 1 regimen of
luteinizing hormone-releasing hormone (LHRH)

- PSA must have risen at least 0.5 ng/mL from baseline on 2 successive
measurements during and/or after hormonal therapy

- PSA greater than 1.0 ng/mL

- If on antiandrogen therapy, must undergo antiandrogen withdrawal for at least 6
weeks and still have evidence of rising PSA

- After prior bicalutamide, must undergo withdrawal for at least 6 weeks and still
have evidence of rising PSA

- Testosterone no greater than 50 ng/mL if no prior orchiectomy

- No metastatic disease by bone scan and CT scan or MRI of the abdomen and pelvis and
by CT scan or x-ray of the chest

- No active or prior CNS metastases

PATIENT CHARACTERISTICS:

Age:

- 18 and over

Performance status:

- Zubrod 0-2 OR

- ECOG 0-2

Life expectancy:

- Not specified

Hematopoietic:

- Absolute lymphocyte count at least 600/mm^3

- Platelet count at least 100,000/mm^3

- Hemoglobin at least 8.0 g/dL

Hepatic:

- Bilirubin no greater than 1.6 mg/dL

- AST and ALT no greater than 4 times normal

Renal:

- Creatinine no greater than 1.5 mg/dL OR

- Creatinine clearance greater than 60 mL/min

- Urinalysis normal OR

- Proteinuria no greater than 1 g/24-hour urine collection

- No hematuria or abnormal sediment unless underlying cause is nonrenal

Immunologic:

- HIV negative

- No altered immune function

- No autoimmune disease, including the following:

- Autoimmune neutropenia, thrombocytopenia, or hemolytic anemia

- Systemic lupus erythematosus, Sjogren's syndrome, or scleroderma

- Myasthenia gravis

- Goodpasture syndrome

- Addison's disease, Hashimoto's thyroiditis, or active Graves' disease

- No known allergy or untoward reaction to prior vaccination with vaccinia virus

- No known allergy to eggs

- No active or prior eczema or other eczematoid skin disorders

- No other acute, chronic, or exfoliative skin conditions (e.g., atopic dermatitis,
impetigo, varicella zoster, burns, severe acne, or other open rashes or wounds)

Other:

- No other serious concurrent illness

- No active infections within the past 3 days

- No history of seizures, encephalitis, or multiple sclerosis

- No close or household contact for at least 2 weeks after each vaccinia virus
inoculation with the following high-risk individuals:

- Children under 5 years of age

- Pregnant or nursing women

- Individuals with active or prior eczema or other eczematoid skin disorders,
atopic dermatitis, impetigo, varicella zoster, burns, severe acne, or other open
rashes or wounds

- Immunosuppressed or immunodeficient (by disease or therapy) individuals,
including those with HIV infection

- No other malignancy within the past 3 years except squamous cell or basal cell skin
cancer or other curatively treated malignancy

PRIOR CONCURRENT THERAPY:

Biologic therapy:

- Must have prior vaccinia for smallpox immunization

- No other concurrent biologic therapy

Chemotherapy:

- No prior chemotherapy for prostate cancer

- No concurrent chemotherapy

Endocrine therapy:

- See Disease Characteristics

- At least 4 weeks since prior hormonal therapy (6 weeks for bicalutamide) and
recovered

- If disease progression on LHRH antagonist, must continue to receive that LHRH agent
or undergo surgical castration

- No concurrent steroids unless topical or inhaled

- No other concurrent hormonal therapy

Radiotherapy:

- At least 4 weeks since prior radiotherapy and recovered

- No prior radiotherapy to more than 50% of nodal groups

- No concurrent radiotherapy

Surgery:

- See Disease Characteristics

- See Endocrine therapy

- At least 4 weeks since prior surgery and recovered

- No prior splenectomy

Other:

- No concurrent homeopathic therapy with PC-SPES or genistein

Type of Study:

Interventional

Study Design:

Allocation: Randomized, Primary Purpose: Treatment

Principal Investigator

Philip M. Arlen, MD

Investigator Role:

Study Chair

Investigator Affiliation:

National Cancer Institute (NCI)

Authority:

United States: Federal Government

Study ID:

CDR0000068106

NCT ID:

NCT00020254

Start Date:

June 2000

Completion Date:

Related Keywords:

  • Prostate Cancer
  • adenocarcinoma of the prostate
  • recurrent prostate cancer
  • Prostatic Neoplasms

Name

Location

Warren Grant Magnuson Clinical Center - NCI Clinical Studies SupportBethesda, Maryland  20892-1182