Nivolumab With or Without Ipilimumab in Treating Patients With Gastrointestinal Stromal Tumor That Is Metastatic or Cannot Be Removed by Surgery

NCT02880020 | Completed Phase 2 DMC FDA Drug

• 2 other identifiers: 16-000525NCI-2016-01004
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

Brief Summary

This randomized phase II trial studies how well nivolumab with or without ipilimumab works in treating patients with gastrointestinal stromal tumor that has spread to other places in the body or cannot be removed by surgery. Monoclonal antibodies, such as nivolumab and ipilimumab, interfere with the ability of tumor cells to grow and spread.

Conditions

Gastrointestinal Stromal Tumor

Outcome Measures

Primary Outcomes (1)

• Overall response rate defined as the number of subjects with a best objective response of confirmed CR or PR divided by the number of subjects

  Will utilize an exact binomial test to compare the RECIST response rate separately within each of the two study arms. Additionally, an exact 95% confidence interval will be constructed within each arm.

  Up to 2 years

Secondary Outcomes (4)

• Clinical benefit rate

  Up to 2 years

• Frequency and severity of AEs assessed by NCI CTCAE v 4.03

  Up to 2 years

• Progression free survival time

  Up to 2 years

• Response rate by Choi criteria

  Up to 2 years

Study Arms (2)

Arm I (nivolumab)

EXPERIMENTAL

Patients receive nivolumab IV over 60 minutes on day 1. Courses repeat every 14 days for up to 2 years in the absence of disease progression or unacceptable toxicity.

Other: Laboratory Biomarker Analysis; Biological: Nivolumab

Arm II (nivolumab, ipilimumab)

EXPERIMENTAL

Patients receive nivolumab IV over 30 minutes on day 1 and ipilimumab IV over 30 minutes every 6 weeks. Courses repeat every 14 days for up to 2 years in the absence of disease progression or unacceptable toxicity.

Biological: Ipilimumab; Other: Laboratory Biomarker Analysis; Biological: Nivolumab

Interventions

Ipilimumab BIOLOGICAL

Given IV

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

Arm II (nivolumab, ipilimumab)

Laboratory Biomarker Analysis OTHER

Correlative studies

Arm I (nivolumab); Arm II (nivolumab, ipilimumab)

Nivolumab BIOLOGICAL

Given IV

Also known as: BMS-936558, MDX-1106, NIVO, ONO-4538, Opdivo

Arm I (nivolumab); Arm II (nivolumab, ipilimumab)

Eligibility Criteria

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

You may qualify if:

• Written informed consent must be obtained from the subject/legal representative prior to performing any protocol-related procedures, including screening evaluations
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1
• Life expectancy \> 12 weeks
• Histological confirmation of GIST
• Mutational testing of patient samples for KIT and platelet-derived growth factor receptor (PDGFR) mutations; (this will not hold up starting therapy, but will be done for all patients lacking up front mutational testing)
• Patients must have refused or have evidence of intolerance to or progression on imatinib
• This study permits the re-enrollment of a subject that has discontinued the study as a pre-treatment failure (i.e., subject has not been randomized / has not been treated); if re-enrolled, the subject must be re-consented
• Adequate archival tissue must be available from the prior 3 months to signing consent; if not, an adequate tumor specimen obtained by either excisional biopsy, incisional biopsy or core needle biopsy must be sent to the central pathology lab for evaluation; the material must measure at least 0.8 × 0.1 cm in size or contain at least 100 tumor cells
• Measurable tumor lesions according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria
• Hemoglobin \>= 9 g/dL
• Absolute neutrophil count \>= 1,500/mm\^3
• Platelet count \>= 100,000/mm\^3
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =\< 2.5 × institutional upper limit of normal (ULN); for subjects with liver metastases, AST or ALT =\< 5 × ULN
• Bilirubin =\< 1.5 × ULN; for subjects with documented/suspected Gilbert's disease, bilirubin =\< 3 × ULN
• Willingness to provide consent for biopsy samples; tumor biopsies will be required for all subjects, tumor lesions used for biopsy should not be lesions used as RECIST target lesions, unless there are no other lesions suitable for biopsy; if a RECIST target lesion is used for biopsy the lesion must be \>= 2 cm in longest diameter

You may not qualify if:

• Palliative surgery and/or radiation treatment within 28 days prior to course 1 day 1 (C1D1)
• Localized therapy of non-target lesions is allowed
• No steroids are permitted within 28 days of C1D1; or doses \< 10mg/day prednisone equivalent or levels necessary for physiologic replacement
• Women who are of pregnant or breastfeeding
• Inability to give informed consent
• An inadequate tumor specimen as defined by the local pathologist
• History of other malignancies except cured basal cell carcinoma, cutaneous squamous cell carcinoma, melanoma in situ, superficial bladder cancer or carcinoma in situ of the cervix; for other malignancies, must be documented to be free of cancer for \>= 2 years; all other cases can be considered on a case by case basis at the discretion of the principal investigator
• Any condition that might interfere with the subject's participation in the study, safety, or in the evaluation of the study results
• Concurrent enrollment in another clinical study, unless it is an observational (non-interventional) clinical study or the follow-up period of an interventional study
• Prior exposure to any anti-PD-1 or anti-PD-L1 antibody, or any anti-cytotoxic T-lymphocyte-associated protein (CTLA) 4 antibodies
• Any concurrent chemotherapy, immunotherapy, biologic or hormonal therapy for cancer treatment; concurrent use of hormones for non-cancer-related conditions (eg, insulin for diabetes and hormone replacement therapy) is acceptable
• Current or prior use of immunosuppressive medication within 28 days before the first dose of nivolumab, with the exceptions of intranasal, topical, and inhaled corticosteroids or systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or equivalent (use for brain metastases is not permitted 28 days prior to start of therapy)
• Active or prior documented autoimmune disease within the past 3 years
• NOTE: subjects with active, known or suspected autoimmune disease such as vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll
• History of organ transplant that requires use of immunosuppressives

Sponsors & Collaborators

• Jonsson Comprehensive Cancer Center: lead
• Bristol-Myers Squibb: collaborator

Study Sites (1)

Rachel Andes

Los Angeles, California, 90095, United States

Location

MeSH Terms

Conditions

Gastrointestinal Stromal Tumors

Interventions

Ipilimumab; CTLA-4 Antigen; Nivolumab

Condition Hierarchy (Ancestors)

Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal 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

Study Officials

• Arun Singh, MD

  UCLA / Jonsson Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 23, 2016
• First Posted: August 26, 2016
• Study Start: December 14, 2016
• Primary Completion: August 9, 2022
• Study Completion: August 9, 2022
• Last Updated: August 18, 2022

Record last verified: 2021-10

Locations

US (1)