Ipilimumab and Sargramostim in Treating Patients With Metastatic Prostate Cancer
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| ClinicalTrials.gov Identifier: NCT00064129 |
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Recruitment Status :
Completed
First Posted : July 9, 2003
Last Update Posted : July 30, 2020
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| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Recurrent Prostate Carcinoma Stage IV Prostate Cancer AJCC v7 | Biological: Ipilimumab Other: Laboratory Biomarker Analysis Other: Pharmacological Study Biological: Sargramostim | Phase 1 |
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.
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 42 participants |
| Allocation: | N/A |
| Intervention Model: | Single Group Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | A Phase I Study of Repetitive Dosing of Anti-CTLA-4 Antibody (Ipilimumab) in Combination With GM-CSF in Patients With Metastatic, Androgen-Independent Prostate Cancer |
| Actual Study Start Date : | May 13, 2003 |
| Actual Primary Completion Date : | January 10, 2011 |
| Actual Study Completion Date : | October 1, 2012 |
| Arm | Intervention/treatment |
|---|---|
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Experimental: Treatment (monoclonal antibody, colony-stimulating factors)
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.
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Biological: Ipilimumab
Given IV
Other Names:
Other: Laboratory Biomarker Analysis Correlative studies Other: Pharmacological Study Correlative studies Biological: Sargramostim Given SC
Other Names:
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- MTD of the combination of ipilimumab with GM-CSF that results in < 33% DLT [ Time Frame: Continuously ]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.
- Adaptive immunity [ 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 ]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.
- PSA and/or objective response for measurable disease [ Time Frame: Day 1 ]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.
- Safety of the regimen [ Time Frame: Continuously ]Graded according to the NCI common toxicity criteria, version 3.0.
- Anti-idiotype antibody (human anti-human antibodies [HAHA]) development [ Time Frame: Baseline, before each ipilimumab infusion and 2 months after the last infusion of antibody ]A semi-quantitative ELISA assay will be used to detect IgG antibodies to Ipilimumab in the plasma samples.
- Pharmacokinetic (PK) Studies [ Time Frame: Prior to and 60 minutes after all infusions, and at 1 and 2 months after the last ipilimumab infusion ]Determined using a quantitative ELISA.
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | Male |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
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Histologically confirmed prostate cancer
- Metastatic disease
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Progressive disease after prior androgen deprivation as defined by at least 1 of the following criteria:
- Patients with measurable disease must have an increase of at least 20% in the sum of the longest diameter of target lesions OR the appearance of 1 or more new lesions
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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*
- At least 1 PSA level must be obtained at least 4 weeks after flutamide (6 weeks after bicalutamide or nilutamide)
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Testosterone no greater than 50 ng/dL
- Patients with no prior orchiectomy must continue luteinizing hormone-releasing hormone agonist therapy
- No history or radiologic evidence of CNS metastases
- Performance status - ECOG 0-2
- At least 12 weeks
- Absolute neutrophil count greater than 1,500/mm^3
- Platelet count at least 100,000/mm^3
- Hemoglobin at least 8 g/dL
- Bilirubin less than 1.5 times upper limit of normal (ULN)
- SGOT and SGPT no greater than 2.5 times ULN
- Creatinine no greater than 1.5 times ULN
- No significant cardiovascular disease
- No New York Heart Association class III or IV congestive heart failure
- No active angina pectoris
- No myocardial infarction within the past 6 months
- Not pregnant or nursing
- Fertile patients must use effective contraception prior to, during, and for 3 months after study participation
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No history of autoimmune disease including, but not limited to, any of the following:
- Autoimmune hemolytic anemia
- Ulcerative and hemorrhagic colitis
- Endocrine disorders (e.g., thyroiditis, hyperthyroidism, hypothyroidism of immune etiology, autoimmune hypophysitis/hypopituitarism, or adrenal insufficiency)
- Sarcoid granuloma
- Myasthenia gravis
- Polymyositis
- Guillain-Barre syndrome
- Systemic lupus erythematosus
- Rheumatoid arthritis
- Inflammatory bowel disease
- No other medical or psychiatric illness that would preclude study participation or giving informed consent
- No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer or stage I or II cancer currently in complete remission
- No prior immunotherapy (e.g., vaccines or investigational)
- No other concurrent colony-stimulating factors
- No prior chemotherapy
- No concurrent chemotherapy
- See Disease Characteristics
- At least 4 weeks since prior systemic corticosteroids
- At least 4 weeks since other prior hormonal therapy, including megestrol and finasteride
- No concurrent systemic steroid therapy except inhaled or topical steroids
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No other concurrent hormonal therapy
- Hormones administered for nondisease-related conditions (e.g., insulin for diabetes) allowed
- At least 4 weeks since prior radiotherapy and recovered
- More than 8 weeks since prior radiopharmaceuticals (e.g., strontium chloride Sr 89 and samarium Sm 153 lexidronam pentasodium)
- Prior irradiation of a symptomatic lesion or one that may produce disability (e.g., unstable femur) allowed
- No concurrent palliative radiotherapy
- See Disease Characteristics
- At least 4 weeks since prior herbal products known to decrease PSA levels (e.g., PC-SPES or saw palmetto)
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00064129
| United States, California | |
| UCSF Medical Center-Mount Zion | |
| San Francisco, California, United States, 94115 | |
| Principal Investigator: | Eric J Small | UCSF Medical Center-Mount Zion |
| Responsible Party: | National Cancer Institute (NCI) |
| ClinicalTrials.gov Identifier: | NCT00064129 |
| Obsolete Identifiers: | NCT01648361 |
| Other Study ID Numbers: |
NCI-2009-00036 NCI-2009-00036 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ) UCSF-02558 CDR0000309054 NCI-6032 02558 ( Other Identifier: UCSF Medical Center-Mount Zion ) 6032 ( Other Identifier: CTEP ) |
| First Posted: | July 9, 2003 Key Record Dates |
| Last Update Posted: | July 30, 2020 |
| Last Verified: | July 2020 |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
| Product Manufactured in and Exported from the U.S.: | No |
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Prostatic Neoplasms Genital Neoplasms, Male Urogenital Neoplasms Neoplasms by Site Neoplasms Genital Diseases, Male Genital Diseases Urogenital Diseases Prostatic Diseases |
Male Urogenital Diseases Ipilimumab Sargramostim Antineoplastic Agents, Immunological Antineoplastic Agents Immune Checkpoint Inhibitors Molecular Mechanisms of Pharmacological Action Immunologic Factors Physiological Effects of Drugs |