Randomized Phase 2 Study of Cabozantinib, Ipilimumab, and Nivolumab in Patients With Soft Tissue Sarcoma

Status: Active_not_recruiting
Location: See all (27) locations...
Intervention Type: Procedure, Drug, Biological
Study Type: Interventional
Study Phase: Phase 2
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.

Eligibility
Participation Requirements
Sex: All
Minimum Age: 18
Healthy Volunteers: f
View:

• Patients must have histologically or cytologically confirmed metastatic STS, specifically undifferentiated pleomorphic sarcoma (UPS), extraskeletal myxoid chondrosarcoma (EMC), liposarcoma (LPS) or non-uterine leiomyosarcoma (LMS) that are locally advanced and surgically unresectable

• Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as \>= 20 mm (\>= 2 cm) by chest x-ray or as \>= 10 mm (\>= 1 cm) with CT scan, MRI, or calipers by clinical exam. Disease will be measured by RECISTv1.1

• Patients with prior treatment with MET or VEGFR inhibitors are allowed. However, prior cabozantinib-treated patients will not be allowed. Prior ipilimumab in combination with nivolumab-treated patients will not be allowed

• Age \>= 18 years

• Eastern Cooperative Oncology Group (ECOG) performance status =\< 2 (Karnofsky \>= 60%)

• Absolute neutrophil count \>= 1,000/mcL

• Platelets \>= 75,000/mcL

• Total bilirubin =\< 1.5 x institutional upper limit of normal (ULN)

• Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT)(serum glutamate pyruvate transaminase \[SGPT\]) =\< 3 x institutional ULN

• Creatinine =\< 1.5 x institutional ULN OR glomerular filtration rate (GFR) \>= 50 mL/min/1.73 m\^2

• Serum albumin \>= 2.8g/dL

• Lipase \< 2.0 x ULN and no radiologic or clinical evidence of pancreatitis

• Urine protein/creatinine ratio (UPCR) =\< 1 mg/mg

• For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy if indicated

• Patients with a history of hepatitis C virus (HCV) infection must have been treated and have undetectable HCV viral load 12 or more weeks after treatment completion. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load

• Patients with treated brain metastases are eligible if follow-up brain imaging after central nervous system (CNS)-directed therapy shows no evidence of progression \>= 1 month after treatment of the brain metastases. Patients with new or progressive brain metastases (active brain metastases) or leptomeningeal disease are eligible if the treating physician determines that immediate CNS specific treatment is not required and is unlikely to be required during the first 2 cycles of therapy

• Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class 2B or better

• Patients must be willing to provide blood specimens and undergo biopsies for research purposes

• Patients with baseline blood pressure (BP) lower than 140 mmHg (systolic) and 90 mmHg (diastolic). Patients on \> 2 anti-hypertensive agents will be excluded

• Human immunodeficiency virus (HIV)-infected patients on effective combination antiretroviral therapy are eligible as long as HIV is well-controlled and there is undetectable viral load within 6 months. For these patients, an HIV viral load test must be completed within 28 days prior to enrollment

• The effects of nivolumab, ipilimumab, and cabozantinib on the developing human fetus are unknown. For this reason and because other therapeutic agents used in this trial are known to be teratogenic, women of child-bearing potential (WOCBP) and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. WOCBP (defined as any female who has experienced menarche and who has not undergone surgical sterilization \[hysterectomy or bilateral oophorectomy\] or who is not postmenopausal) should use an adequate method to avoid pregnancy for 5 months after the last dose of investigational drug. Women of childbearing potential must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin \[HCG\]) at the time of enrollment and within 8 days prior to each cycle. Women must not be breastfeeding

• Men who are sexually active with women of child-bearing potential (WOCBP) must use any contraceptive method with a failure rate of less than 1% per year. Men receiving cabozantinib and who are sexually active with WOCBP will be instructed to adhere to contraception for a period of 5 months after the last dose of investigational product. Women who are not of childbearing potential (i.e., who are postmenopausal or surgically sterile) as well as azoospermic men do not require contraception

• Ability to understand and the willingness to sign a written informed consent document

Locations
United States
California
City of Hope Comprehensive Cancer Center
Duarte
UCI Health - Chao Family Comprehensive Cancer Center and Ambulatory Care
Irvine
Keck Medicine of USC Koreatown
Los Angeles
Los Angeles General Medical Center
Los Angeles
USC / Norris Comprehensive Cancer Center
Los Angeles
USC Norris Oncology/Hematology-Newport Beach
Newport Beach
UC Irvine Health/Chao Family Comprehensive Cancer Center
Orange
Connecticut
Smilow Cancer Hospital Care Center at Saint Francis
Hartford
Yale University
New Haven
Smilow Cancer Hospital Care Center-Trumbull
Trumbull
Washington, D.c.
MedStar Georgetown University Hospital
Washington D.c.
Florida
University of Florida Health Science Center - Gainesville
Gainesville
Maryland
National Cancer Institute Developmental Therapeutics Clinic
Bethesda
National Institutes of Health Clinical Center
Bethesda
Missouri
Siteman Cancer Center-South County
St Louis
Washington University School of Medicine
St Louis
North Carolina
UNC Lineberger Comprehensive Cancer Center
Chapel Hill
New York
Laura and Isaac Perlmutter Cancer Center at NYU Langone
New York
Ohio
Ohio State University Comprehensive Cancer Center
Columbus
Oklahoma
University of Oklahoma Health Sciences Center
Oklahoma City
Pennsylvania
University of Pittsburgh Cancer Institute (UPCI)
Pittsburgh
Tennessee
Vanderbilt University/Ingram Cancer Center
Nashville
Texas
M D Anderson Cancer Center
Houston
Utah
Huntsman Cancer Institute/University of Utah
Salt Lake City
Virginia
University of Virginia Cancer Center
Charlottesville
VCU Massey Comprehensive Cancer Center
Richmond
Other Locations
Canada
University Health Network-Princess Margaret Hospital
Toronto
Time Frame
Start Date: 2023-10-25
Completion Date: 2026-05-15
Participants
Target number of participants: 66
Treatments
Active_comparator: Arm A (nivolumab, ipilimumab)
Patients receive nivolumab IV over 30-60 minutes and ipilimumab IV over 60-90 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 over 30 minutes 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 and urine samples throughout the trial. Patients can crossover from Arm A to Arm B at the time of disease progression.
Experimental: Arm B (cabozantinib, nivolumab, ipilimumab)
Patients receive cabozantinib PO QD or QOD, nivolumab IV over 30-60 minutes on day 1, and ipilimumab IV over 60-90 minutes 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 over 30 minutes on day 1 and cabozantinib PO QD or QOD of subsequent cycles. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients crossing over after ≥ 4 ipilimumab + nivolumab (Arm A) cycles will receive cabozantinib and nivolumab only on Arm B; patients that cross over after \< 4 ipilimumab + nivolumab (Arm A) cycles will receive the remaining cycles of ipilimumab (totaling 4 doses) plus nivolumab in combination with cabozantinib. Patients who crossover start with the every 3 weeks cycle 1 treatment even if they will not be receiving ipilimumab. Patients also undergo CT or MRI scans, tumor biopsies, and collection of blood and urine samples throughout.
Sponsors
Leads: National Cancer Institute LAO

This content was sourced from clinicaltrials.gov