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

NCT01510288 | Terminated Phase 1 DMC

• 1 other identifier: G-0016
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Prostate Cancer

Keywords

GVAX; Ipilimumab; prostate cancer

Outcome Measures

Primary Outcomes (1)

• Number of patients with adverse events

  7 months

Secondary Outcomes (3)

• number of patients that have a tumor/PSA response

  7 months

• number of patients that will develop a tumor-specific (e.g. PSMA, NY-ESO) antibody response as measured by ELISA

  7 months

• the number of patients that have activated T cells and dendritic cells as measured by FACS

  7 months

Study Arms (1)

Ipilimumab and GVAX

EXPERIMENTAL

Drug: GVAX and ipilimumab

Interventions

GVAX and ipilimumab DRUG

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.

Ipilimumab and GVAX

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Amsterdam UMC, location VUmc: lead
• Cell Genesys: collaborator
• Medarex: collaborator

Study Sites (1)

VU university medical center

Amsterdam, 1081 HV, Netherlands

Location

Related Publications (1)

• van den Eertwegh AJ, Versluis J, van den Berg HP, Santegoets SJ, van Moorselaar RJ, van der Sluis TM, Gall HE, Harding TC, Jooss K, Lowy I, Pinedo HM, Scheper RJ, Stam AG, von Blomberg BM, de Gruijl TD, Hege K, Sacks N, Gerritsen WR. Combined immunotherapy with granulocyte-macrophage colony-stimulating factor-transduced allogeneic prostate cancer cells and ipilimumab in patients with metastatic castration-resistant prostate cancer: a phase 1 dose-escalation trial. Lancet Oncol. 2012 May;13(5):509-17. doi: 10.1016/S1470-2045(12)70007-4. Epub 2012 Feb 10.

  PMID: 22326922 DERIVED

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

Ipilimumab

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Winald Gerritsen, Prof. MD PhD

  Amsterdam UMC, location VUmc

  PRINCIPAL INVESTIGATOR

• Fons van den Eertwegh, MD PhD

  Amsterdam UMC, location VUmc

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Dr.

Study Record Dates

• First Submitted: January 4, 2012
• First Posted: January 16, 2012
• Study Start: November 1, 2004
• Primary Completion: December 1, 2007
• Study Completion: November 1, 2011
• Last Updated: January 16, 2012

Record last verified: 2012-01

Locations

NL (1)