Ipilimumab and Sargramostim in Treating Patients With Metastatic Prostate Cancer

NCT00064129 | Completed Phase 1 FDA Drug

• 6 other identifiers: NCI-2009-00036UCSF-02558CDR0000309054NCI-6032025586032
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Recurrent Prostate Carcinoma; Stage IV Prostate Cancer AJCC v7

Outcome Measures

Primary Outcomes (1)

• 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.

  Continuously

Secondary Outcomes (5)

• Adaptive immunity

  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

  Day 1

• Safety of the regimen

  Continuously

• Anti-idiotype antibody (human anti-human antibodies [HAHA]) development

  Baseline, before each ipilimumab infusion and 2 months after the last infusion of antibody

• Pharmacokinetic (PK) Studies

  Prior to and 60 minutes after all infusions, and at 1 and 2 months after the last ipilimumab infusion

Study Arms (1)

Treatment (monoclonal antibody, colony-stimulating factors)

EXPERIMENTAL

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

Interventions

Ipilimumab BIOLOGICAL

Given IV

Also known as: Anti-Cytotoxic T-Lymphocyte-Associated Antigen-4 Monoclonal Antibody, BMS-734016, MDX-010, MDX-CTLA4, Yervoy

Treatment (monoclonal antibody, colony-stimulating factors)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (monoclonal antibody, colony-stimulating factors)

Pharmacological Study OTHER

Correlative studies

Treatment (monoclonal antibody, colony-stimulating factors)

Sargramostim BIOLOGICAL

Given SC

Also known as: 23-L-Leucinecolony-Stimulating Factor 2, DRG-0012, Leukine, Prokine, rhu GM-CFS, Sagramostim, Sargramostatin

Treatment (monoclonal antibody, colony-stimulating factors)

Eligibility Criteria

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

You may qualify if:

• Histologically confirmed prostate cancer
• Metastatic disease
• 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
• 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)
• 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)

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

UCSF Medical Center-Mount Zion

San Francisco, California, 94115, United States

Location

Related Publications (2)

• Cham J, Zhang L, Kwek S, Paciorek A, He T, Fong G, Oh DY, Fong L. Combination immunotherapy induces distinct T-cell repertoire responses when administered to patients with different malignancies. J Immunother Cancer. 2020 May;8(1):e000368. doi: 10.1136/jitc-2019-000368.

  PMID: 32376721 DERIVED

• Kavanagh B, O'Brien S, Lee D, Hou Y, Weinberg V, Rini B, Allison JP, Small EJ, Fong L. CTLA4 blockade expands FoxP3+ regulatory and activated effector CD4+ T cells in a dose-dependent fashion. Blood. 2008 Aug 15;112(4):1175-83. doi: 10.1182/blood-2007-11-125435. Epub 2008 Jun 3.

  PMID: 18523152 DERIVED

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

Ipilimumab; CTLA-4 Antigen; sargramostim; Colony-Stimulating Factors

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; Immune Checkpoint Proteins; Costimulatory and Inhibitory T-Cell Receptors; Receptors, Immunologic; Receptors, Cell Surface; Membrane Proteins; Antigens, Differentiation, T-Lymphocyte; Antigens, Differentiation; Antigens, Surface; Antigens; Biological Factors; Biomarkers; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides

Study Officials

• Eric J Small

  UCSF Medical Center-Mount Zion

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 8, 2003
• First Posted: July 9, 2003
• Study Start: May 13, 2003
• Primary Completion: January 10, 2011
• Study Completion: October 1, 2012
• Last Updated: July 30, 2020

Record last verified: 2020-07

Locations

US (1)