Phase 1 Trial of Ipilimumab and GVAX in Patients With Metastatic Castration-resistant Prostate Cancer

• Status: Terminated
• Trial end date: 2011-11-01
• Target enrollment: 0
• Participant gender: Male

Summary

Ipilimumab, an antibody that blocks cytotoxic T-lymphocyte antigen 4, and GVAX have demonstrated anti-tumor activity in prostate cancer. Pre-clinical studies with this combination have demonstrated potent synergy. The purpose of this study is to investigate, using a phase-I 3+3 dose escalation design followed by an expansion cohort, the safety and efficacy of combined treatment with GVAX and ipilimumab in castration-resistant metastatic prostate cancer (CRPC) patients.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: VU University Medical Center
• Collaborators: Cell Genesys; Medarex
• Treatments: Antibodies, Monoclonal; Ipilimumab

Criteria

Inclusion Criteria:

• Males age 18-80 years

• Histologic diagnosis of adenocarcinoma of the prostate

• Metastatic prostate cancer deemed to be unresponsive or refractory to hormone therapy

• Detectable metastases by bone scan, CT scan or MRI

• Two consecutive rising PSA values obtained at least two weeks apart and both obtained at least 4-6 weeks after discontinuation of hormone therapy. Second PSA value must be > 5.0 ng/mL. LHRH agonist should not be discontinued.

• Testosterone < 50 ng/dL. Must have had orchiectomy or is currently receiving an LHRH agonist.

• WBC > 3.0 x 109/L, ANC > 1.5 x 109/L, hemoglobin > 6.2 mmol/L, and platelets > 100 x 109/L

• Serum creatinine < 177 umol/L Bilirubin < 1.5 times the upper limit of normal AST < 3 times the upper limit of normal

• ECOG performance status 0-2

• Life expectancy of at least 6 months

• If sexually active, willing to use barrier contraception during the treatment phase of the protocol

• The ability to understand and willingness to sign a written informed consent

Exclusion Criteria:

• Transitional cell, small cell, neuroendocrine, or squamous cell prostate cancer

• Bone pain severe enough to require routine narcotic analgesia use

• Clinical evidence of brain metastases or history of brain metastases

• Seropositive for HIV, Hepatitis B antigen positive and/or Hepatitis C viremic

• Prior chemotherapy or immunotherapy for prostate cancer

• Radiation therapy within 4 weeks of the first treatment

• Surgery within 4 weeks of the first treatment. Must have recovered from all side effects.

• Flutamide within 4 weeks of the first treatment Megesterol acetate (Megace), finasteride (Proscar), bicalutamide (Casodex),nilutamide, aminoglutethimide, ketoconazole or diethylstilbestrol within 6 weeks of the first treatment.

• Systemic corticosteroid use within 4 weeks of the first treatment

• History of autoimmune disease

• History of another malignancy, except for the following: adequately treated basal cell or squamous cell skin cancer, superficial bladder cancer, adequately treated Stage I or II cancer currently in complete remission or any other cancer that has been in complete remission for at least 5 years