Vaccine Therapy in Treating Patients With Metastatic Prostate Cancer

Duke University

Status and phase: Terminated; Phase 1

Conditions: Prostate Cancer

Treatments: Biological: therapeutic autologous dendritic cells

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT00010127

NCI-G00-1910

DUMC-000759-00-4R1

0759

CDR0000068447 (Other Identifier)

DUMC-DORIS-99043

Details and patient eligibility

About

RATIONALE: Vaccines made from a person's cancer cells may make the body build an immune response to kill prostate tumor cells.

PURPOSE: Phase I trial to study the effectiveness of vaccine therapy in treating patients who have metastatic prostate cancer.

Full description

OBJECTIVES:

• Determine the safety and feasibility of autologous dendritic cells transfected with autologous total tumor RNA in patients with metastatic prostate cancer.
• Determine the presence, frequency, and activation status of tumor specific and prostate specific antigen (PSA) specific cellular immune responses in patients treated with this regimen.
• Determine delayed-type hypersensitivity reactions to PSA protein and other recall antigens in patients before and after being treated with this regimen.
• Determine clinical responses based on clinical and biochemical (PSA) response criteria in patients treated with this regimen.
• Determine a platform for immunological treatment using dendritic-cell based tumor vaccines in these patients.

OUTLINE: This is a dose escalation study.

Tumor tissue and peripheral blood stem cells are collected from patients and cultured in vitro with sargramostim (GM-CSF) and interleukin-4 for 7 days to produce dendritic cells (DC). Patients receive autologous DC transfected with autologous prostate carcinoma RNA intradermally once weekly on weeks 0-3 for a total of 4 doses.

Cohorts of 3-6 patients receive escalating doses of DC 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.

Patients are followed at weeks 6, 8, 10, and 12; every 3 months for 9 months; and then annually for 2 years.

PROJECTED ACCRUAL: A total of 18 patients will be accrued for this study within 20 months.

Enrollment: 3 patients

Sex: Male

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed metastatic adenocarcinoma of the prostate

  • Stage D1-3
  • Regional lymph node, bone, visceral, or soft tissue metastases
  • No transitional cell or small cell carcinoma

• Testosterone less than 50 mg/L if prior treatment with luteinizing hormone releasing hormone (LHRH) analogues or estrogens

• Evidence of androgen refractory disease after surgical castration and discontinuation of LHRH analogue therapy

• No previously irradiated or new CNS metastases

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Performance status:

• Karnofsky 70-100%

Life expectancy:

• More than 6 months

Hematopoietic:

• WBC at least 3,000/mm^3
• Hemoglobin at least 9 g/dL
• Platelet count at least 100,000/mm^3

Hepatic:

• Bilirubin less than 2.0 mg/dL
• PT at least 11.3 seconds but no greater than 13.3 seconds
• PTT at least 20.1 seconds but no greater than 32.9 seconds
• No hepatic disease
• No viral hepatitis

Renal:

• Creatinine less than 2.5 mg/dL

Cardiovascular:

• No New York Heart Association class III or IV heart disease

Pulmonary:

• No asthma
• No chronic obstructive pulmonary disease
• No severe lung disease

Other:

• No other medical illness or psychological impediment that would preclude study
• No other concurrent malignancy except nonmelanoma skin cancer or controlled superficial bladder cancer
• No active acute or chronic infection including symptomatic urinary tract infection
• No autoimmune disease (e.g., inflammatory bowel disease, systemic lupus erythematosus, rheumatoid arthritis, ankylosing spondylitis, scleroderma, or multiple sclerosis)
• HIV negative
• Adequate peripheral vein access

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Prior biologic therapy allowed
• No other concurrent immunotherapy

Chemotherapy:

• Prior chemotherapy allowed
• No concurrent chemotherapy

Endocrine therapy:

• See Disease Characteristics
• At least 4 weeks since prior non-steroidal hormonal therapy if increase in PSA while receiving non-steroidal hormonal therapy
• At least 6 weeks since prior steroids
• Concurrent LHRH analogues for gonadal androgen suppression allowed
• No concurrent steroid therapy
• No concurrent corticosteroids

Radiotherapy:

• See Disease Characteristics
• Prior palliative radiotherapy for bone metastases allowed
• Prior prostatic radiotherapy allowed
• At least 4 weeks since prior radiotherapy
• At least 12 weeks since prior strontium chloride Sr 89
• No concurrent radiotherapy

Surgery:

• See Disease Characteristics

Other:

• Recovered from prior therapy
• No concurrent immunosuppressive agents (e.g., azathioprine or cyclosporine)