Metastatic Malignant Solid Neoplasm, Unresectable Solid Neoplasm
Conditions
Brief summary
This phase II trial studies the effect of nivolumab in treating patients with solid tumors that have spread to other places in the body (metastatic) or cannot be removed by surgery (unresectable) with RID1A mutation and CXCL13 expression. Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving nivolumab may help to control the disease.
Detailed description
PRIMARY OBJECTIVES: I. To estimate objective response rate (ORR) and overall survival (OS) in patients with ARID1A mutations receiving nivolumab therapy. II. To estimate objective response rate (ORR) and overall survival (OS) in patients with ARID1A mutations plus CXCL13-high expression and ARID1A mutations plus CXCL13-low expression, receiving nivolumab therapy. SECONDARY OBJECTIVES: I. To estimate progression free survival (PFS) in subjects with harboring ARID1A mutation treated with nivolumab monotherapy. II. To estimate progression free survival (PFS) in subjects with ARID1A mutations plus CXCL13-high expression and ARID1A mutations plus CXCL13-low expression, treated with nivolumab monotherapy. III. To assess peripheral and tumor infiltrating immune cell sub-populations in patients with ARID1A mutations, ARID1A plus CXCL13-high and ARID1A plus CXCL13-low expression, to determine predictors of response and resistance. IV. To determine expression pattern of CXCL13 in ARID1A mutant tumors. OUTLINE: Patients receive nivolumab and relatlimab IV over 30 minutes on day 1 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo computed tomography (CT) or magnetic resonance imaging (MRI), tissue biopsy and blood sample collection during screening and on the trial.
Interventions
BIOLOGICALNivolumab
Given IV
Sponsors
M.D. Anderson Cancer Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
Inclusion criteria
* Patient will have a tumor harboring genomic mutation of ARID1A * Histological or cytological evidence of metastatic or surgically unresectable disease harboring ARID1A mutation * All subjects must have measurable disease by computed tomography (CT) or magnetic resonance imaging (MRI) per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria * Evaluable tumor tissue (archived or new biopsy) must be provided for biomarker analysis as formalin-fixed paraffin-embedded (FFPE) tumor block or minimum of 10 slides. Archived tissue may be from prior biopsy of unresectable or metastatic disease or from prior surgical resection * Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1 * Prior palliative radiotherapy must have been completed at least 2 weeks prior to study drug administration. Patients must have measurable disease outside the radiation field to be eligible. Patients with progression in a previously radiated field will also be eligible * White blood cell (WBC) \>= 2000/uL (obtained within 7 days prior to first dose) * Neutrophils \>= 1500/uL (obtained within 7 days prior to first dose) * Platelets \>= 100 x 1 x 10\^3/uL (obtained within 7 days prior to first dose) * Hemoglobin \>= 9.0 g/dL (obtained within 7 days prior to first dose) * Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =\< 3 x upper limit of normal (ULN) (or =\< 5 X ULN for participants with liver metastases) (obtained within 7 days prior to first dose) * Total bilirubin =\< 1.5 x ULN (except subjects with Gilbert Syndrome, who can have total bilirubin \< 3.0 mg/dL) (obtained within 7 days prior to first dose) * Serum creatinine =\< 1.5 x ULN or creatinine clearance (CrCl) \>= 30 mL/min (using the Cockcroft-Gault formula) (obtained within 7 days prior to first dose) * Re-enrollment: This study permits the re-enrollment of a subject that has discontinued the study as a pre-treatment failure (ie, subject has not been treated). If re-enrolled, the subject must be re-consented and inclusion/
Exclusion criteria
reassessed * Patients are required to participate in PA13-0291 for correlative studies. Patients will need to consent for biopsy and peripheral blood collection as documented in the study calendar * Patients must be ≥18 years of age at enrollment.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective response rate (ORR) | Up to 2 years | Defined as the rate of confirmed complete responses (CR) + partial responses (PR) as determined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria and as assessed by the investigator. Will estimate ORR along with the 95% exact confidence interval (CI) |
| Overall survival (OS) | From date of first study treatment to death due to any cause, assessed up to 2 years | Kaplan-Meier method will be used to estimate the median OS and 1-year Survival Rate; the 95% CI of the 1-year survival rate will also be reported. Censoring for the survival endpoint will be assigned on the date of the last on-study follow-up that the patient is reported to be alive. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORFunda Meric-Bernstam
M.D. Anderson Cancer Center
Outcome results
None listed