Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Trial Contact Information
Registry Information

Alternate Title

Vaccine Therapy in Treating Patients With Advanced Adenocarcinoma of the Prostate (Prostate Cancer)

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase II Treatment Completed 18 and over NCI DFCI-98262 NCI-T98-0004, NCT00005039, T98-0004

Objectives

1. Determine the toxicity and maximum tolerated dose of recombinant fowlpox prostate-specific antigen (PSA) vaccine in patients with advanced adenocarcinoma of the prostate.
2. Determine whether vaccination with recombinant fowlpox-PSA vaccine is associated with antitumor activity in these patients.
3. Determine the efficacy of prime and boost regimens using recombinant fowlpox-PSA vaccine and recombinant vaccinia-PSA vaccine in these patients.
4. Compare the PSA-specific T-cell response in patients treated with recombinant fowlpox-PSA vaccine followed by recombinant vaccinia-PSA vaccine vs the same vaccines but in reverse order.

Entry Criteria

Disease Characteristics:

• Histologically proven adenocarcinoma of the prostate with evidence of metastatic disease including any of the following:
  • Lymph node positive and prostate-specific antigen (PSA) at least 10 ng/mL
  • Bone scan positive and PSA at least 10 ng/mL
  • Prior radical prostatectomy with rising PSA and PSA at least 2 ng/mL
  • Prior radiotherapy and PSA at least 10 ng/mL
  • Prior cryosurgery and PSA at least 10 ng/mL
    • PSA criteria does not apply to patients who are assigned to group B of this study and were previously treated on vaccine trial DFCI-96079



• No symptomatic metastatic disease (no bony pain)



• Complete HLA typing required

Prior/Concurrent Therapy:

Biologic therapy:

• See Disease Characteristics
• See Endocrine therapy
• Prior vaccinia (smallpox) immunization required
• No other concurrent biologic therapy (e.g., interferon or interleukin) for cancer

Chemotherapy:

• No prior chemotherapy for metastatic disease
• No concurrent anticancer chemotherapy

Endocrine therapy:

• No prior hormonal therapy for metastatic disease
• Prior neoadjuvant hormonal therapy followed by prostatectomy or radiotherapy allowed
• Patients previously treated with recombinant vaccinia-PSA vaccine may have hormonal therapy since discontinuing that treatment (Group B)
• No concurrent hormonal therapy or steroids

Radiotherapy:

• See Disease Characteristics
• See Endocrine therapy
• No concurrent radiotherapy

Surgery:

• See Disease Characteristics
• See Endocrine therapy
• No prior splenectomy

Other:

• At least 3 days since prior antibiotics
• No concurrent immunosuppressive treatment (e.g., after organ transplantation)

Patient Characteristics:

Age:

• 18 and over

Performance status:

• ECOG 0 or 1

Life expectancy:

• Not specified

Hematopoietic:

• WBC greater than 2,000/mm³
• Platelet count greater than 100,000/mm³

Hepatic:

• Bilirubin less than 2.0 mg/dL
• SGPT less than 4 times upper limit of normal

Renal:

• Creatinine less than 4.0 mg/dL

Immunologic:

• No altered immune function such as eczema
• No autoimmune diseases such as the following:
  • Autoimmune neutropenia, thrombocytopenia, or hemolytic anemia
  • Systemic lupus erythematosus, Sjögren's syndrome, or scleroderma
  • Myasthenia gravis
  • Goodpasture's syndrome
  • Addison's disease, Hashimoto's thyroiditis, or active Graves' disease
• HIV negative
• No allergy or untoward reaction to prior vaccinia (smallpox) vaccination
• No hypersensitivity to eggs

Other:

• No prior or concurrent extensive eczema or skin disorders (e.g., extensive psoriasis, burns, impetigo, or disseminated zoster)
• No other concurrent serious illness
• No active infection requiring antibiotics until infection has cleared and antibiotics have been stopped for at least 3 days
• Fertile patients must use effective contraception
• No close contact or household contact with the following high-risk individuals for at least 2 weeks after each vaccination:
  • Children under age 5
  • Pregnant or nursing women
  • Individuals with prior or concurrent extensive eczema or other eczematoid skin disorders
  • Individuals with other acute, chronic, or exfoliative skin conditions (e.g., atopic dermatitis, burns, impetigo, varicella zoster, severe acne, or other open rashes or wounds)
  • Immunodeficient or immunosuppressed individuals (by disease or therapy) such as those with HIV infection

Expected Enrollment

Approximately 6-86 patients (6 in the safety cohort, 15-20 per arm in group A, and approximately 10 in group B) will be accrued for this study within 1 year.

Outline

This is a randomized, open-label, multicenter, dose-escalation study of recombinant fowlpox prostate-specific antigen (PSA) vaccine.

• Safety cohort: The first cohort of 3 patients receives vaccination with recombinant fowlpox-PSA vaccine intramuscularly (IM). Treatment repeats every 4 weeks for 3 courses. In the absence of unacceptable toxicity in the first cohort, the second cohort of 3 patients receives the same vaccine at the dose level immediately higher than the first cohort dose level. In the presence of unacceptable toxicity in the first cohort, the second cohort of 3 patients receives the same vaccine at a dose level lower than the first cohort dose level. The maximum tolerated dose (MTD) is the dose preceding that at which 1 of 6 patients experiences grade 3 or worse dose-limiting toxicity.

Subsequent patients are assigned to one of two vaccination groups based on prior treatment with recombinant vaccinia-PSA vaccine:

• Group A (no prior recombinant vaccinia-PSA vaccine): Patients are randomized to one of two vaccination arms:
  • Arm I: Patients receive recombinant fowlpox-PSA vaccine IM at the MTD from the safety cohort every 4 weeks for 3 courses. Patients then receive recombinant vaccinia-PSA vaccine intradermally every 4 weeks for 2 courses.
  
  
  
  • Arm II: Patients receive the same vaccines as in arm I but in reverse order.
  
  
  



• Group B (prior recombinant vaccinia-PSA vaccine): Patients receive treatment as in arm I, group A.



• Groups A and B: Patients with stable or responding disease at 6 months after completion of vaccination therapy may continue treatment on the group and arm to which they were originally assigned. Treatment repeats every 6-9 months in the absence of disease progression.

Patients are followed monthly for 6 months and then every 3 months thereafter.

Trial Contact Information

Trial Lead Organizations

Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute

Joseph Paul Eder, MD, Protocol chair		Ph: 617-632-5588; 866-790-4500 Email: joseph_eder@dfci.harvard.edu

Registry Information
Official Title		A Phase II Randomized Trial of Recombinant Fowlpox and Recombinant Vaccinia Virus Expressing PSA in Patients with Adenocarcinoma of the Prostate
Trial Start Date		2000-01-04
Registered in ClinicalTrials.gov		NCT00005039
Date Submitted to PDQ		2000-02-04
Information Last Verified		2003-11-23
NCI Grant/Contract Number		CA06516, CA62490