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

This study has been terminated.
(The study was terminated because Cell Genesys stopped all activities for GVAX.)
Sponsor:
Collaborators:
Cell Genesys
Medarex
Information provided by (Responsible Party):
A.J.M. van den Eertwegh, VU University Medical Center
ClinicalTrials.gov Identifier:
NCT01510288
First received: January 4, 2012
Last updated: January 10, 2012
Last verified: January 2012
History of Changes
  Purpose

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.


Condition Intervention Phase
Prostate Cancer
 Drug: GVAX and ipilimumab
 Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 1 Dose Escalation Trial of Ipilimumab in Combination With CG1940 and CG8711 in Patients With Metastatic Hormone-Refractory Prostate Cancer

Resource links provided by NLM:

Drug Information available for: Ipilimumab
U.S. FDA Resources

Further study details as provided by VU University Medical Center:

Primary Outcome Measures:
  • Number of patients with adverse events [ Time Frame: 7 months ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • number of patients that have a tumor/PSA response [ Time Frame: 7 months ] [ Designated as safety issue: No ]
  • number of patients that will develop a tumor-specific (e.g. PSMA, NY-ESO) antibody response as measured by ELISA [ Time Frame: 7 months ] [ Designated as safety issue: No ]
  • the number of patients that have activated T cells and dendritic cells as measured by FACS [ Time Frame: 7 months ] [ Designated as safety issue: No ]

Enrollment: 28
Study Start Date: November 2004
Study Completion Date: November 2011
Primary Completion Date: December 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Ipilimumab and GVAX Drug: GVAX and ipilimumab
All patients receive a 500 million cell priming dose of granulocyte-macrophage colony-stimulating factor-transduced allogeneic prostate cancer cells (GVAX) intradermally on day 1 followed by bi-weekly intradermal injections of 300 million cells for a 24 week period. The vaccinations are combined with monthly intravenous administrations of ipilimumab. The dose-escalation part of this study will be performed using the standard 3+3 phase-I trial design. Patients will be enrolled in cohorts of three; each cohort will receive an escalating dose of ipilimumab at 0•3, 1•0, 3•0 or 5•0 mg/kg. Sixteen patients will be treated in an expansion cohort with GVAX and 3•0 mg/kg ipilimumab.

Detailed 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.

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01510288

Locations
Netherlands
VU university medical center
Amsterdam, Netherlands, 1081 HV
Sponsors and Collaborators
VU University Medical Center
Cell Genesys
Medarex
Investigators
Principal Investigator: Winald Gerritsen, Prof. MD PhD VU University Medical Center
Principal Investigator: Fons van den Eertwegh, MD PhD VU University Medical Center
  More Information

No publications provided by VU University Medical Center

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Responsible Party: A.J.M. van den Eertwegh, Dr., VU University Medical Center
ClinicalTrials.gov Identifier: NCT01510288     History of Changes
Other Study ID Numbers: G-0016
Study First Received: January 4, 2012
Last Updated: January 10, 2012
Health Authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Keywords provided by VU University Medical Center:
GVAX
Ipilimumab
prostate cancer

Additional relevant MeSH terms:
Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
 Neoplasms
Genital Diseases, Male
Prostatic Diseases

ClinicalTrials.gov processed this record on May 23, 2013