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Brief Title: Testing Ipilimumab and Nivolumab Combination With or Without Cabozantinib in People >= 18 Years Old With Advanced Soft Tissue Sarcoma
Official Title: Randomized Phase 2 Study of Cabozantinib, Ipilimumab, and Nivolumab in Patients With Soft Tissue Sarcoma
Study ID: NCT05836571
Brief Summary: This phase II trial compares the effect of immunotherapy with ipilimumab and nivolumab alone to their combination with cabozantinib in treating patients with soft tissue sarcoma that has spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced). Immunotherapy with monoclonal antibodies, such as ipilimumab and nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Cabozantinib is in a class of medications called kinase inhibitors. It works by blocking the action of an abnormal protein that signals cancer cells to multiply and may also prevent the growth of new blood vessels that tumors need to grow. By these actions it may help slow or stop the spread of cancer cells. Adding cabozantinib to the combination of ipilimumab and nivolumab may be better in stopping or slowing the growth of tumor compared to ipilimumab and nivolumab alone in patients with advanced soft tissue sarcoma.
Detailed Description: PRIMARY OBJECTIVE: I. Assess progression free survival (PFS) of ipilimumab + nivolumab versus (vs.) the cabozantinib + nivolumab + ipilimumab combination in patients with metastatic, or locally advanced, surgically unresectable soft tissue sarcoma (STS) using Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1. SECONDARY OBJECTIVES: I. Evaluate the response rate (complete response \[CR\]+partial response \[PR\]) of ipilimumab + nivolumab vs. the cabozantinib + nivolumab + ipilimumab combination. II. Evaluate the response rate (CR+PR) of cabozantinib + ipilimumab + nivolumab in (crossover) patients whose disease has progressed on ipilimumab + nivolumab therapy. III. Assess the number of tumor-infiltrating CD8+ T cells in tumor biopsies before and after treatment. EXPLORATORY OBJECTIVES: I. Measure tumor-infiltrating CD3+ T cells and CD68+ macrophages in biopsy specimens. II. Evaluate genomic alterations in circulating tumor DNA (ctDNA) and their potential association with therapy response or resistance. III. Investigate whether response is associated with genetic aberrations and/or tumor mutational burden. IV. Analyze total MET and activated MET (p1235-MET) in biopsy specimens before and after study treatment and evaluate molecular target engagement by cabozantinib (as shown by a lower phosphorylated \[p\]MET/MET ratio). V. Evaluate the objective response rate in patients treated with ipilimumab + nivolumab or the cabozantinib + nivolumab + ipilimumab combination using immune-modified Response Evaluation Criteria in Solid Tumors (iRECIST). OUTLINE: Patients are randomized to 1 of 2 arms. ARM A: Patients receive nivolumab intravenously (IV) over 30 minutes and ipilimumab IV over 30-60 minutes on day 1 of each cycle. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity for 4 cycles. Patients then receive nivolumab IV on day 1 of subsequent cycles. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo computed tomography (CT) or magnetic resonance imaging (MRI) scans, tumor biopsies, and collection of blood throughout the trial. ARM B: Patients receive cabozantinib orally (PO) once daily (QD) in the absence of disease progression or unacceptable toxicity. Patients receive nivolumab IV and ipilimumab IV on day 1 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity for 4 cycles. Patients then receive nivolumab IV on day 1 of subsequent cycles. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT or MRI scans, tumor biopsies, and collection of blood throughout the trial. After completion of study treatment, patients are followed for 30 days.
Minimum Age: 18 Years
Eligible Ages: ADULT, OLDER_ADULT
Sex: ALL
Healthy Volunteers: No
City of Hope Comprehensive Cancer Center, Duarte, California, United States
Keck Medicine of USC Koreatown, Los Angeles, California, United States
Los Angeles General Medical Center, Los Angeles, California, United States
USC / Norris Comprehensive Cancer Center, Los Angeles, California, United States
USC Norris Oncology/Hematology-Newport Beach, Newport Beach, California, United States
UC Irvine Health/Chao Family Comprehensive Cancer Center, Orange, California, United States
MedStar Georgetown University Hospital, Washington, District of Columbia, United States
National Cancer Institute Developmental Therapeutics Clinic, Bethesda, Maryland, United States
National Institutes of Health Clinical Center, Bethesda, Maryland, United States
Washington University School of Medicine, Saint Louis, Missouri, United States
Siteman Cancer Center-South County, Saint Louis, Missouri, United States
Ohio State University Comprehensive Cancer Center, Columbus, Ohio, United States
University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States
University of Pittsburgh Cancer Institute (UPCI), Pittsburgh, Pennsylvania, United States
M D Anderson Cancer Center, Houston, Texas, United States
Virginia Commonwealth University/Massey Cancer Center, Richmond, Virginia, United States
University Health Network-Princess Margaret Hospital, Toronto, Ontario, Canada
Name: A P Chen
Affiliation: National Cancer Institute LAO
Role: PRINCIPAL_INVESTIGATOR