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

Primary Purpose

Prostate Cancer

Status
Terminated
Phase
Phase 1
Locations
Netherlands
Study Type
Interventional
Intervention
GVAX and ipilimumab
Sponsored by
Amsterdam UMC, location VUmc
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Prostate Cancer focused on measuring GVAX, Ipilimumab, prostate cancer

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)MaleDoes not accept 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

Sites / Locations

  • VU university medical center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Ipilimumab and GVAX

Arm Description

Outcomes

Primary Outcome Measures

Number of patients with adverse events

Secondary Outcome Measures

number of patients that have a tumor/PSA response
number of patients that will develop a tumor-specific (e.g. PSMA, NY-ESO) antibody response as measured by ELISA
the number of patients that have activated T cells and dendritic cells as measured by FACS

Full Information

First Posted
January 4, 2012
Last Updated
January 10, 2012
Sponsor
Amsterdam UMC, location VUmc
Collaborators
Cell Genesys, Medarex
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1. Study Identification

Unique Protocol Identification Number
NCT01510288
Brief Title
Phase 1 Trial of Ipilimumab and GVAX in Patients With Metastatic Castration-resistant Prostate Cancer
Official Title
A Phase 1 Dose Escalation Trial of Ipilimumab in Combination With CG1940 and CG8711 in Patients With Metastatic Hormone-Refractory Prostate Cancer
Study Type
Interventional

2. Study Status

Record Verification Date
January 2012
Overall Recruitment Status
Terminated
Why Stopped
The study was terminated because Cell Genesys stopped all activities for GVAX.
Study Start Date
November 2004 (undefined)
Primary Completion Date
December 2007 (Actual)
Study Completion Date
November 2011 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Amsterdam UMC, location VUmc
Collaborators
Cell Genesys, Medarex

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Prostate Cancer
Keywords
GVAX, Ipilimumab, prostate cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
28 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Ipilimumab and GVAX
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
GVAX and ipilimumab
Intervention Description
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.
Primary Outcome Measure Information:
Title
Number of patients with adverse events
Time Frame
7 months
Secondary Outcome Measure Information:
Title
number of patients that have a tumor/PSA response
Time Frame
7 months
Title
number of patients that will develop a tumor-specific (e.g. PSMA, NY-ESO) antibody response as measured by ELISA
Time Frame
7 months
Title
the number of patients that have activated T cells and dendritic cells as measured by FACS
Time Frame
7 months

10. Eligibility

Sex
Male
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Winald Gerritsen, Prof. MD PhD
Organizational Affiliation
Amsterdam UMC, location VUmc
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Fons van den Eertwegh, MD PhD
Organizational Affiliation
Amsterdam UMC, location VUmc
Official's Role
Principal Investigator
Facility Information:
Facility Name
VU university medical center
City
Amsterdam
ZIP/Postal Code
1081 HV
Country
Netherlands

12. IPD Sharing Statement

Citations:
PubMed Identifier
22326922
Citation
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.
Results Reference
derived

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

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