Vaccine Therapy in Treating Patients With Metastatic Prostate Cancer

NCT ID: NCT00004029

Last Updated: 2013-02-11

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 46 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 1996-12-31

Brief Summary

Phase I trial to study the effectiveness of vaccine therapy in treating patients with metastatic prostate cancer. Vaccines may make the body build an immune response to kill tumor cells.

Detailed Description

OBJECTIVES:

I. Assess the toxicity associated with repeated vaccination with recombinant vaccinia virus expressing prostate-specific antigen (rV-PSA) in patients with metastatic adenocarcinoma of the prostate.

II. Determine the optimal dose of rV-PSA given at monthly intervals based on cellular and hormonal immunity.

III. Determine whether vaccination with rV-PSA is associated with anti-tumor activity.

IV. Determine whether granulocyte-macrophage colony-stimulating factor (GM-CSF) has an effect on cellular and humoral immunity different from rV-PSA, and whether the addition of GM-CSF has enhanced antitumor effect compared to rV-PSA alone.

OUTLINE: This is an open label, dose escalation study.

Patients in cohorts of 3-6 receive 3 vaccinations with rV-PSA at 4-week intervals (days 1, 29, 57, and 85) in the absence of disease progression or unacceptable toxicity. Response assessment is performed at eight weeks. Patients who discontinue therapy prior to eight weeks are considered unevaluable for response. If dose limiting toxicity is observed in 2 of 6 patients entered at a dose level, no further patients are entered at that level and the MTD is defined as the preceding dose level. Ten additional patients are treated at the MTD and receive granulocyte-macrophage colony-stimulating factor (GM-CSF) administered subcutaneously on day -1 through day 2 of each cycle. Patients who are HLA-A2 positive, have received all 3 rV-PSA vaccinations without unacceptable toxicity, and have been off study for at least 30 days due to disease progression may continue treatment with rV-PSA at the highest dose level and the addition of GM-CSF.

Patients are followed monthly for 6 months.

Conditions

Prostate Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm I

atients in cohorts of 3-6 receive 3 vaccinations with rV-PSA at 4-week intervals (days 1, 29, 57, and 85) in the absence of disease progression or unacceptable toxicity. Response assessment is performed at eight weeks. Patients who discontinue therapy prior to eight weeks are considered unevaluable for response. If dose limiting toxicity is observed in 2 of 6 patients entered at a dose level, no further patients are entered at that level and the MTD is defined as the preceding dose level. Ten additional patients are treated at the MTD and receive granulocyte-macrophage colony-stimulating factor (GM-CSF) administered subcutaneously on day -1 through day 2 of each cycle. Patients who are HLA-A2 positive, have received all 3 rV-PSA vaccinations without unacceptable toxicity, and have been off study for at least 30 days due to disease progression may continue treatment with rV-PSA at the highest dose level and the addition of GM-CSF.

Group Type: EXPERIMENTAL

recombinant viral vaccine therapy

Intervention Type: BIOLOGICAL

sargramostim

Intervention Type: BIOLOGICAL

Interventions

recombinant viral vaccine therapy

Intervention Type: BIOLOGICAL

sargramostim

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion Criteria

DISEASE CHARACTERISTICS:

• Histologically proven adenocarcinoma of the prostate with evidence of metastatic disease based on any of the following:

• Lymph node positive and PSA at least 10 ng/mL
• Bone scan positive and PSA at least 10 ng/mL
• PSA at least 2 ng/mL and rising following radical prostatectomy
• PSA at least 10 ng/mL following radiotherapy
• No symptomatic metastatic disease (bony pain)

PATIENT CHARACTERISTICS:

• Age: 18 and over
• Performance status: ECOG 0 or 1
• WBC greater than 2,000/mm3
• Platelet count greater than 100,000/mm3
• Bilirubin less than 2.0 mg/dL
• AST less than 4 times normal
• Creatinine less than 2.0 mg/dL
• Must be type HLA-A2 Prior vaccinia (smallpox) exposure required
• At least normal delayed type hypersensitivity to mumps and Candida
• At least normal CD4:CD8 ratio (greater than 1)
• At least normal lymphocyte proliferation testing (to Con A)
• At least normal immunoglobulin levels
• No evidence of altered immune responsiveness or autoimmune syndromes (e.g., scleroderma, systemic lupus erythematosus)
• No HIV antibody No prior splenectomy
• No known allergy to eggs
• No active extensive skin disorders (e.g, psoriasis, burns, impetigo, disseminated zoster)
• No other serious intercurrent illness
• No active infections unless cleared and at least 3 days since antibiotic therapy
• No close contact for 2 weeks after each vaccination with the following people:

• Children less than 3 years old
• Pregnant women
• Individuals with eczema or skin conditions listed above
• Immunosuppressed individuals

PRIOR CONCURRENT THERAPY:

• No concurrent biologic therapy
• No prior chemotherapy for metastatic disease
• No prior hormone therapy for metastatic disease
• Neoadjuvant hormone therapy prior to prostatectomy or radiotherapy allowed
• No concurrent steroids or hormonal medications
• Prior radiotherapy allowed
• Prior surgery allowed

• Minimum Eligible Age: 18 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Donald W. Kufe, MD

Role: STUDY_CHAIR

Dana-Farber Cancer Institute

Locations

Massachusetts General Hospital Cancer Center

Boston, Massachusetts, United States

Brigham and Women's Hospital

Boston, Massachusetts, United States

Dana-Farber Cancer Institute

Boston, Massachusetts, United States

Countries

United States

References

Eder JP Jr, Kantoff PW, Bubley GJ, et al.: A phase I trial of recombinant prostate specific antigen expressing vaccinia virus vaccine, PROSTVAC (rV-PSA) in advanced prostate cancer. [Abstract] Proceedings of the American Society of Clinical Oncology 18: A1692, 439, 1999.

Reference Type: RESULT

Eder JP Jr, Kantoff PW, Bubley GJ, et al.: A phase I trial of recombinant vaccinia virus, PROSTVAC that expresses prostate specific antigen (rV-PSA) as a vaccine in men with advanced prostate cancer. [Abstract] Proceedings of the American Society of Clinical Oncology 17: A1672, 434, 1998.

Reference Type: RESULT

Other Identifiers

DFCI-96079

Identifier Type: -

Identifier Source: secondary_id

NCI-T95-0086H

Identifier Type: -

Identifier Source: secondary_id

CDR0000065275

Identifier Type: -

Identifier Source: org_study_id