ARID1A and/or KDM6A Mutation and CXCL13 Expression
United States6 participantsStarted 2021-09-21
Plain-language summary
This phase II trial studies the effect of nivolumab in urothelial cancer that has spread to other places in the body (metastatic), specifically in patients with aberrations in ARID1A gene (ARID1A mutation) and correlate with expression level of CXCL13, an immune cytokine. 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 control the disease in patients with urothelial cancer or solid tumors. This trial aims at enriching patient selection based on genomic and immunological attributes of the tumor.
Who can participate
Age range18 Years
SexALL
See this in plain English?
AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.
Inclusion criteria
✓. Participants will have a tumor harboring genomic mutation of ARID1A and/or KDM6A. ARID1A and/or KDM6A mutation testing will be performed as standard of care.
✓. Histological or cytological evidence of metastatic or surgically unresectable urothelial cell carcinoma of the urothelial involving the bladder, urethra, ureter, or renal pelvis. Minor histologic variants (\< 50% overall) are acceptable.
✓. Participants must have progression or recurrence after treatment i) with at least 1 platinum-containing chemotherapy regimen for metastatic or surgically unresectable locally advanced urothelial cancer, or ii) are ineligible or refused frontline chemotherapy.
✓. All participants must have measurable disease by CT or MRI per RECIST 1.1 criteria.
✓. Evaluable tumor tissue (archived or new biopsy) must be provided for biomarker analysis as 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. Request for available archival tissue must be in process prior to registration.
✓. 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. Participants with progression in a previously radiated field will also be eligible.
What they're measuring
1
Objective response rate (ORR)
Timeframe: Up to 2 years
2
Overall survival (OS)
Timeframe: From date of first study treatment to death due to any cause, assessed up to 2 years
✓. Screening laboratory values must meet the following criteria and must be obtained within 7 days prior to first dose:
Exclusion criteria
✕. Participants are required to participate in PA13-0291 for correlative studies. Participants will need to consent for biopsy and peripheral blood collection as documented in the study calendar.
✕0. Females of childbearing potential (FCBP) must agree to follow instructions for method(s) of contraception from the time of enrollment, for the duration of study treatment, and for 5 months after the last study dose of study treatment (see Section 8.5).
✕1. Males who are sexually active with FCBP must agree to follow instructions for method(s) of contraception for the duration of study treatment (see Section 8.5). Male participants should refrain from donating sperm during the study.
✕2. FCBP must have a negative serum or urine pregnancy test within 24 hours prior to the start of study treatment.
✕. Prior treatment with an anti-PD-1, anti-PD-L1, anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways.
✕. Active brain metastases or leptomeningeal metastases. Participants with brain metastases are eligible if these have been treated and there is no magnetic resonance imaging (MRI) evidence of progression for at least 4 weeks after treatment is complete and within 14 days prior to first dose of study drug administration. Where MRI is contraindicated CT scan is acceptable. Cases must be discussed with the medical monitor. Brain lesions are not considered measurable disease. There must also be no requirement for immunosuppressive doses of systemic corticosteroids (\> 10 mg/day prednisone equivalents) for at least 2 weeks prior to study drug administration.
✕. Any serious or uncontrolled medical disorder, that in the opinion of the investigator, may increase the risk associated with study participation or study drug administration, impair the ability of the participant to receive protocol therapy, or interfere with the interpretation of study results.
✕. Prior malignancy active within the previous 3 years except for locally curable cancers that have been apparently cured, such as basal or squamous cell skin cancer, prostate cancer without evidence of PSA progression or carcinoma in situ such as the following: gastric, prostate, cervix, colon, melanoma, or breast for example.