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

Amsterdam UMC, location VUmc

Status and phase

Terminated

Phase 1

Conditions

Prostate Cancer

Treatments

Drug: GVAX and ipilimumab

Study type

Interventional

Funder types

Other

Industry

Identifiers

NCT01510288

G-0016

Details and patient eligibility

About

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.

Full description

A promising immunotherapeutic approach in prostate cancer is whole-cell vaccination. Irradiated allogeneic tumor cells expressing GM-CSF generate a long-lasting and specific anti-tumor immunity in preclinical models. Results from several phase I and II trials showed Prostate GVAX (GVAX) to be well tolerated and suggested improved survival. Cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) is a crucial immune checkpoint molecule that down-regulates T-cell activation and proliferation. Ipilimumab, a fully human monoclonal antibody (IgG1) that blocks CTLA-4, promotes antitumor immunity, and has been demonstrated in two phase III trials to improve overall survival in metastatic melanoma patients. Pre-clinical studies of the anti-CTLA-4 antibody in combination with GM-CSF secreting tumor cell vaccines demonstrated a potent synergy. In this phase I study the investigators examine in CRPC patients whether ipilimumab can be safely combined with GVAX. In addition, the investigators will treat an additional 16 patients at a dose level of 3•0 mg/kg to determine the safety profile and antitumor effects of GVAX and ipilimumab in patients with CRPC.

Enrollment

28 patients

Sex

Male

Ages

18 to 80 years old

Volunteers

No Healthy Volunteers

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