Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Published Results
Related Publications
Trial Contact Information
Registry Information

Alternate Title

Vaccine Therapy Plus Sargramostim and Interleukin-2 Compared With Nilutamide Alone in Treating Patients With Prostate Cancer

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase II Treatment Closed 18 and over NCI NCI-00-C-0137 MB-NAVY-99-04, NCI-T99-0097, T99-0097, NCT00020254

Objectives

1. 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.
2. 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.

Entry 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

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

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/mm³
• Platelet count at least 100,000/mm³
• 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

Expected Enrollment

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

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.

Arlen PM, Gulley JL, Todd N, et al.: Antiandrogen, vaccine and combination therapy in patients with nonmetastatic hormone refractory prostate cancer. J Urol 174 (2): 539-46, 2005.[PUBMED Abstract]

Arlen PM, Gulley JL, Novik L, et al.: A randomized phase II trial of either vaccine therapy (recombinant pox viruses expressing PSA and the B7.1 costimulatory molecule) versus hormone therapy (nilutamide) in patients with hormone refractory prostate cancer and no radiographic evidence of disease. [Abstract] J Urol 169 (4 Suppl): A-941, 243, 2003.

Arlen PM, Gulley J, Novik L, et al.: A randomized phase II trial of either vaccine therapy (recombinant pox viruses expressing PSA and the B7.1 costimulatory molecule) versus hormone therapy (nilutamide) in patients (pts) with hormone refractory prostate cancer and no radiographic evidence of disease. [Abstract] Proceedings of the American Society of Clinical Oncology 21: A-728, 2002.

Tsang KY, Zhu M, Even J, et al.: The infection of human dendritic cells with recombinant avipox vectors expressing a costimulatory molecule transgene (CD80) to enhance the activation of antigen-specific cytolytic T cells. Cancer Res 61 (20): 7568-76, 2001.[PUBMED Abstract]

Trial Contact Information

Trial Lead Organizations

NCI - Center for Cancer Research-Medical Oncology

Philip Arlen, MD, Protocol chair		Ph: 301-496-0629

Registry Information
Official Title		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
Trial Start Date		2000-06-29
Registered in ClinicalTrials.gov		NCT00020254
Date Submitted to PDQ		2000-06-28
Information Last Verified		2003-04-21