A Phase 1 interventional study of Ipilimumab and Laboratory Biomarker Analysis in Recurrent Prostate Carcinoma and Stage IV Prostate Cancer AJCC v7, sponsored by National Cancer Institute (NCI). Completed at 1 site in United States. Open to male participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2020-07-30.
Sponsored by National Cancer Institute (NCI) · Phase 1, Interventional, and Treatment
This phase I trial is studying the side effects and best dose of ipilimumab when given with sargramostim in treating patients with metastatic prostate cancer. Monoclonal antibodies can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. Colony-stimulating factors, such as sargramostim, may increase the number of immune cells found in bone marrow or peripheral blood and may help a person's immune system kill more tumor cells.
PRIMARY OBJECTIVES:
I. Determine the maximum tolerated dose of anti-cytotoxic T-lymphocyte-associated antigen-4 monoclonal antibody (MDX-010) (ipilimumab) administered with sargramostim (GM-CSF) in patients with metastatic androgen-independent prostate cancer. (Phase I) II. Determine the safety of this regimen in these patients. (Phase I) III. Evaluate the efficacy as measured by reduction in PSA associated with combining GM-CSF with CTLA-4 blockade with ipilimumab at a dosage of 3 mg/kg given monthly x 6 doses (d1 of courses 1-6). (Cohort Expansion)
SECONDARY OBJECTIVES:
I. Determine the T-cell immunity and T-cell response in patients treated with this regimen. (Phase I) II. Determine the pharmacokinetics of MDX-010 in these patients. (Phase I) III. Determine the prostate-specific antigen and/or objective responses in patients treated with this regimen. (Phase I) IV. Determine the percentages of activated, naive, and memory T-cells. (Cohort Expansion) V. Determine the measurement of T-cell response to describe epitopes from prostate antigens including PSA, PSMA, and PAP. (Cohort Expansion) VI. Quantitate T-cell response to antigens in patients with relevant HLA allele using HLA*0201 tetramers. (Cohort Expansion) VII. Evaluate the toxicity of this regimen in these patients. (Cohort Expansion) VIII. Determine the initial efficacy as measured by reduction in PSA associated with combining GM-CSF with CTLA-4 blockade with ipilimumab at a dosage of 3 mg/kg given monthly x 6 doses (d1 of courses 1-6). (Cohort Expansion) IX. Determine objective response by post-therapy measurable disease changes using RECIST criteria. (Cohort Expansion)
OUTLINE: This is a multicenter, dose-escalation study of ipilimumab.
Patients receive ipilimumab intravenously (IV) over 90 minutes on day 1 and sargramostim (GM-CSF) subcutaneously (SC) on days 1-14. Treatment repeats every 28 days for 4-6 courses. GM-CSF continues beyond 4 courses in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of ipilimumab until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Some patients undergo blood sample collection periodically for laboratory and pharmacokinetic studies. Samples are analyzed for human anti-human antibodies, IgG antibodies to ipilimumab semi-quantitative ELISA assay, and plasma concentrations of ipilimumab via quantitative ELISA assay.
Patients are followed at 30 days.
6,370 studies on the registry are indexed under Prostatic Neoplasms; 1,397 are open to participants now.
This study's enrollment of 42 is below the median of 58 across 4,821 interventional studies indexed under Prostatic Neoplasms.
Browse Prostatic Neoplasms studies →National Cancer Institute (NCI) is the lead sponsor of 3,506 studies on the registry; 334 are open to participants now.
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Inclusion Criteria:
Histologically confirmed prostate cancer
Progressive disease after prior androgen deprivation as defined by at least 1 of the following criteria:
Patients with nonmeasurable disease must have a positive bone scan and a prostate-specific antigen (PSA) level of at least 5 ng/mL, which has risen on at least 2 successive occasions at least 2 weeks apart*
Testosterone no greater than 50 ng/dL
No history of autoimmune disease including, but not limited to, any of the following:
No other concurrent hormonal therapy
Patients receive ipilimumab IV over 90 minutes on day 1 and sargramostim (GM-CSF) SC on days 1-14. Treatment repeats every 28 days for 4-6 courses. GM-CSF continues beyond 4 courses in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of ipilimumab until the MTD is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Some patients undergo blood sample collection periodically for laboratory and pharmacokinetic studies. Samples are analyzed for human anti-human antibodies, IgG antibodies to ipilimumab semi-quantitative ELISA assay, and plasma concentrations of ipilimumab via quantitative ELISA assay.
Biological: Ipilimumab · Other: Laboratory Biomarker Analysis · Other: Pharmacological Study · Biological: Sargramostim
Given IV
Also known as: Anti-Cytotoxic T-Lymphocyte-Associated Antigen-4 Monoclonal Antibody, BMS-734016, MDX-010, MDX-CTLA4, Yervoy
Correlative studies
Correlative studies
Given SC
Also known as: 23-L-Leucinecolony-Stimulating Factor 2, DRG-0012, Leukine, Prokine, rhu GM-CFS, Sagramostim, Sargramostatin
MTD of the combination of ipilimumab with GM-CSF that results in < 33% DLT
Graded according to the National Cancer Institute (NCI) common toxicity criteria, version 3.0. Results will be tabulated by dose cohort and overall for this trial. DLT is defined by any of the following that are attributable to therapy: any \>= grade 4 toxicity, any ocular toxicity considered immune mediated and requiring systemic steroids, any grade 3 toxicity considered immune mediated that cannot be controlled with systemic steroids.
Time frame: Continuously
Adaptive immunity
Measured through peripheral blood collection. Three and four-color immunofluorescence and flow cytometric analysis will be employed to determine relative numbers of activated T cells. Specifically, percentages of T cells (CD3+, CD4+ or CD8+) expressing the activation markers HLA-DR, CD25 and CD69 will be determined. Also, percentages of naive (CD45RA+) and memory (CD45RO+) T cells will be determined.
Time frame: Baseline, days 1 and 14 of courses 1 and 2, day 1 of courses 3-6, and then day 1 of every other course throughout treatment
PSA and/or objective response for measurable disease
Evaluated according to Response Evaluation Criteria in Solid Tumors (RESIST) criteria. PSA Response will be evaluated according to the recommendations from National Cancer Institute PSA Working Group. 95% confidence interval will be provided.
Time frame: Day 1
Safety of the regimen
Graded according to the NCI common toxicity criteria, version 3.0.
Time frame: Continuously
Anti-idiotype antibody (human anti-human antibodies [HAHA]) development
A semi-quantitative ELISA assay will be used to detect IgG antibodies to Ipilimumab in the plasma samples.
Time frame: Baseline, before each ipilimumab infusion and 2 months after the last infusion of antibody
Pharmacokinetic (PK) Studies
Determined using a quantitative ELISA.
Time frame: Prior to and 60 minutes after all infusions, and at 1 and 2 months after the last ipilimumab infusion
This study is completed, as verified in Jul 2020. You cannot join it, but the record below documents what was studied.
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National Cancer Institute (NCI)