- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01510288
Phase 1 Trial of Ipilimumab and GVAX in Patients With Metastatic Castration-resistant Prostate Cancer
January 10, 2012 updated by: A.J.M. van den Eertwegh, Amsterdam UMC, location VUmc
A Phase 1 Dose Escalation Trial of Ipilimumab in Combination With CG1940 and CG8711 in Patients With Metastatic Hormone-Refractory Prostate Cancer
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.
Study Overview
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.
Study Type
Interventional
Enrollment (Actual)
28
Phase
- Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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Amsterdam, Netherlands, 1081 HV
- VU University Medical Center
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years to 80 years (ADULT, OLDER_ADULT)
Accepts Healthy Volunteers
No
Genders Eligible for Study
Male
Description
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
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: NA
- Interventional Model: SINGLE_GROUP
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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EXPERIMENTAL: Ipilimumab and GVAX
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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.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Number of patients with adverse events
Time Frame: 7 months
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7 months
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Secondary Outcome Measures
Outcome Measure |
Time Frame |
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number of patients that have a tumor/PSA response
Time Frame: 7 months
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7 months
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number of patients that will develop a tumor-specific (e.g. PSMA, NY-ESO) antibody response as measured by ELISA
Time Frame: 7 months
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7 months
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the number of patients that have activated T cells and dendritic cells as measured by FACS
Time Frame: 7 months
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7 months
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Investigators
- Principal Investigator: Winald Gerritsen, Prof. MD PhD, Amsterdam Umc, Location Vumc
- Principal Investigator: Fons van den Eertwegh, MD PhD, Amsterdam Umc, Location Vumc
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
November 1, 2004
Primary Completion (ACTUAL)
December 1, 2007
Study Completion (ACTUAL)
November 1, 2011
Study Registration Dates
First Submitted
January 4, 2012
First Submitted That Met QC Criteria
January 10, 2012
First Posted (ESTIMATE)
January 16, 2012
Study Record Updates
Last Update Posted (ESTIMATE)
January 16, 2012
Last Update Submitted That Met QC Criteria
January 10, 2012
Last Verified
January 1, 2012
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- G-0016
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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