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

Alternate Title

Vaccine Therapy in Treating Patients With Progressive or Locally Recurrent Prostate Cancer

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase I	Treatment	Closed	18 and over	NCI	NCI-05-C-0017 NCI-6066, 6066, NCT00098449

Special Category: NCI Web site featured trial

Objectives

Primary

1. Determine the clinical safety and feasibility of vaccine therapy comprising priming vaccinations of vaccinia-PSA-TRICOM and recombinant fowlpox-GM-CSF (rF-GM-CSF) followed by boosting vaccinations of fowlpox-PSA-TRICOM with or without rF-GM-CSF in patients with progressive or locally recurrent prostate cancer.

Secondary

1. Determine changes in prostate-specific antigen-specific T-cell response in HLA-A2-positive patients treated with this regimen.

Entry Criteria

Disease Characteristics:

• Histologically confirmed* adenocarcinoma of the prostate, meeting 1 of the following criteria:
  • Locally recurrent disease after prior local radiotherapy or cryotherapy, defined as 3 consecutive rising prostate-specific antigen levels AND confirmed by biopsy performed ≥ 18 months after completion of radiotherapy
  • Not a candidate for or refused local definitive therapy (surgery or radiation therapy) AND had clinically progressive disease during androgen deprivation therapy, defined as 3 increases in PSA over nadir, separated by ≥ 1 week

   [Note: *Patients without a pathological specimen available are eligible provided there is histologic diagnosis of prostate cancer and a clinical course consistent with prostate disease]




• Minimal extraprostatic disease allowed



• No clinically active brain metastases

Prior/Concurrent Therapy:

Biologic therapy

• No prior vaccinia unless immune to vaccinia
• No other concurrent immunotherapy

Chemotherapy

• No concurrent anticancer chemotherapy

Endocrine therapy

• See Disease Characteristics
• No steroid eye drops for at least 2 weeks before, during, and for at least 4 weeks after study treatment
• Concurrent hormonal therapy allowed
• No concurrent systemic steroids, including glucocorticoids, except for physiologic doses for systemic steroid replacement or local (i.e., topical, nasal, or inhaled) steroid use

Radiotherapy

• See Disease Characteristics
• At least 4 weeks since prior radiotherapy
• No concurrent radiotherapy

Surgery

• See Disease Characteristics
• At least 4 weeks since prior surgery
• No prior splenectomy
• No concurrent major surgery

Other

• Recovered from all prior therapy

Patient Characteristics:

Age

• 18 and over

Performance status

• ECOG 0-2

Life expectancy

• At least 6 months

Hematopoietic

• Granulocyte count ≥ 1,500/mm³
• Platelet count ≥ 100,000/mm³
• Lymphocyte count ≥ 500/mm³
• Hemoglobin ≥ 10 g/dL

Hepatic

• Bilirubin < 1.5 mg/dL (≤ 3.0 mg/dL for patients with Gilbert's syndrome)
• AST and ALT < 2.5 times upper limit of normal
• Hepatitis B and C negative

Renal

• Creatinine < 2.0 mg/dL OR creatinine clearance > 60 mL/min
• No proteinuria, defined as ≥ 1,000 mg of protein on 24-hour urine collection
• No abnormal urine sediment or hematuria unless the underlying cause is determined to be non-renal

Cardiovascular

• No New York Heart Association class II-IV heart disease
• No objective evidence of congestive heart failure by physical exam or imaging

Pulmonary

• No pulmonary disease that causes fatigue or dyspnea during ordinary physical activity

Neurologic

• No history of seizures
• No history of encephalitis
• No history of multiple sclerosis

Gastrointestinal

• No inflammatory bowel disease
• No Crohn's disease
• No ulcerative colitis
• No active diverticulitis

Immunologic

• HIV negative
• History of autoimmunity not requiring systemic immunosuppressive therapy and not threatening vital organ function (e.g., CNS, heart, lungs, kidneys, skin, or gastrointestinal tract) allowed
• No active autoimmune disease, including any of the following:
  • Addison's disease
  • Hashimoto's thyroiditis
  • Systemic lupus erythematosus
  • Sjögren's syndrome
  • Scleroderma
  • Myasthenia gravis
  • Goodpasture's syndrome
  • Graves' disease
• No other altered immune function, including any of the following conditions:
  • History of or active eczema or other eczematoid skin disorders
  • Atopic dermatitis
  • Other skin diseases
  • Open wounds
• No history of allergy or untoward reaction to prior vaccination with vaccinia virus or any component of study treatment
• No serious hypersensitivity to egg products

Other

• Fertile patients must use effective contraception during and for at least 4 months after study treatment
• Able to avoid close household contact with any of the following for at least 3 weeks after each study vaccination:
  • Individuals with a history of or active eczema or other eczematoid skin disorders
  • Individuals with acute, chronic, or exfoliative skin conditions (e.g., atopic dermatitis, burns, impetigo, varicella zoster, severe acne, or other open rashes or wounds) until the condition resolves
  • Pregnant or nursing women
  • Children age 3 and under
  • Immunodeficient or immunosuppressed (by disease or therapy) individuals, including HIV-positive individuals
• No other malignancy within the past year except nonmelanoma skin cancer or carcinoma in situ of the bladder
• No other life-threatening illness
• No other serious medical illness that would preclude study participation

Expected Enrollment

A total of 3-30 patients will be accrued for this study within 30 months.

Outcomes

Safety by CTCAE v 3.0 continuously

Compare immunologic response by ELISPOT at baseline and at day 113
Prostate-specific antigen (PSA) changes by monthly serum PSA

Outline

This is a dose-escalation study of booster vaccinations comprising vaccinia-PSA-TRICOM (rV-PSA-TRICOM) with or without recombinant fowlpox-GM-CSF (rF-GM-CSF). Patients are assigned to 1 of 5 groups.

• Groups 1 and 2: Patients receive priming vaccinations comprising rV-PSA-TRICOM subcutaneously (SC) and rF-GM-CSF SC on day 1. Patients also receive a booster vaccination comprising fowlpox-PSA-TRICOM (rF-PSA-TRICOM) by intraprostatic (IP) injection on days 29, 57, and 85.



• Groups 3 and 4: Patients receive priming and booster vaccinations as in groups 1 and 2. Patients also receive a booster vaccination comprising rF-GM-CSF IP on days 29, 57, and 85.



• Group 5: Patients receive priming and booster vaccinations as in groups 3 and 4. Patients also receive booster vaccinations comprising rF-PSA-TRICOM SC and rF-GM-CSF SC on days 29, 57, and 85.

Cohorts of 3-6 patients in each group receive escalating doses of booster vaccinations comprising rF-PSA-TRICOM with or without rF-GM-CSF until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

Treatment in all groups continues in the absence of unacceptable toxicity or disease progression.

Patients are followed annually for up to 15 years.

Trial Contact Information

Trial Lead Organizations

NCI - Center for Cancer Research

James Gulley, MD, PhD, Principal investigator		Ph: 301-435-2956 Email: gulleyj@mail.nih.gov

Related Information

Featured trial article
Web site for additional information

Registry Information
Official Title		A Phase I Feasibility Study of an Intraprostatic PSA-Based Vaccine in Men With Prostate Cancer and Local Failure Following Radiotherapy or Cryotherapy or Clinical Progression on Androgen Deprivation Therapy in the Absence of Local Definitive Therapy
Trial Start Date		2004-11-15
Trial Completion Date		2006-02-08 (estimated)
Registered in ClinicalTrials.gov		NCT00098449
Date Submitted to PDQ		2004-10-20
Information Last Verified		2008-04-04