ACTIVE_NOT_RECRUITING

Testing Ipilimumab and Nivolumab Combination With or Without Cabozantinib in People >= 18 Years Old With Advanced Soft Tissue Sarcoma

Conditions

Locally Advanced Extraskeletal Myxoid Chondrosarcoma Locally Advanced Leiomyosarcoma Locally Advanced Liposarcoma Locally Advanced Undifferentiated Pleomorphic Sarcoma Locally Advanced Unresectable Soft Tissue Sarcoma Metastatic Soft Tissue Sarcoma Metastatic Undifferentiated Pleomorphic Sarcoma Unresectable Leiomyosarcoma Unresectable Liposarcoma Unresectable Undifferentiated Pleomorphic Sarcoma

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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.

Official Title

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

Quick Facts

Study Start:2023-10-25

Study Completion:2026-05-15

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:ACTIVE_NOT_RECRUITING

Study ID

NCT05836571

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
* 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	* Patients who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities \> grade 1) with the exception of alopecia, stable hyperthyroidism on replacement therapy, type-1 diabetes, well-controlled on insulin, and non-clinically significant toxicities at the discretion of the study Principal Investigator * Patients who are receiving any other investigational agents * Eligibility of subjects receiving any medications or substances known to affect or with the potential to affect the activity of cabozantinib will be determined following review of their cases by the Principal Investigator. Patients who are taking enzyme-inducing anticonvulsant agents are not eligible * History of allergic reactions attributed to compounds of similar chemical or biologic composition to cabozantinib, nivolumab, or ipilimumab * Patients receiving any medications or substances that are strong inhibitors or inducers of CYP3A4 are ineligible. Strong CYP3A4 inducers (e.g., phenytoin, carbamazepine, rifampin, rifabutin, rifapentine, phenobarbital, and St. John's Wort) are not allowed for this study. Because the lists of these agents are constantly changing, frequently updated lists available at http://medicine.iupui.edu/clinpharm/ddis/table.asp or other reliable resources will be consulted. Patients who need to come off CYP3A4 inhibitors/inducers should adhere to a washout period of at least 5 times the half-life of the CYP3A4 inhibitors and 14 days of CYP3A4 inducers * Patients with any other significant condition(s) that would make this protocol unreasonably hazardous are ineligible. Patients with uncontrolled intercurrent illness or clinical evidence of an active infection at the time of enrollment are ineligible * Pregnant women are excluded from this study because cabozantinib is a receptor kinase inhibitor agent with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with cabozantinib in combination with nivolumab and ipilimumab, breastfeeding should be discontinued if the mother is treated with cabozantinib. These potential risks may also apply to other immunotherapeutic agents (ipilimumab and nivolumab) used in this study * Patients with any of the following within 12 weeks prior to the first dose of cabozantinib: gastrointestinal bleeding, hemoptysis or pulmonary hemorrhage, radiographic evidence of cavitating pulmonary lesion(s), evidence of tumor invasion of the gastrointestinal (GI) tract (esophagus, stomach, small or large bowel, rectum, or anus), or any evidence of endotracheal or endobronchial tumor or encasement of any major blood vessels are ineligible * The patient is unable to swallow tablets * The patient has a corrected QT interval calculated by the Fridericia formula (QTcF) \>= 470 ms within 28 days before enrollment * Patients with a requirement for steroid or immunosuppressive treatment should be excluded if they have a condition requiring systemic treatment with either corticosteroids (\> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids and adrenal replacement doses \> 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease

Inclusion Criteria

Exclusion Criteria

* 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

* Patients who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities \> grade 1) with the exception of alopecia, stable hyperthyroidism on replacement therapy, type-1 diabetes, well-controlled on insulin, and non-clinically significant toxicities at the discretion of the study Principal Investigator
* Patients who are receiving any other investigational agents
* Eligibility of subjects receiving any medications or substances known to affect or with the potential to affect the activity of cabozantinib will be determined following review of their cases by the Principal Investigator. Patients who are taking enzyme-inducing anticonvulsant agents are not eligible
* History of allergic reactions attributed to compounds of similar chemical or biologic composition to cabozantinib, nivolumab, or ipilimumab
* Patients receiving any medications or substances that are strong inhibitors or inducers of CYP3A4 are ineligible. Strong CYP3A4 inducers (e.g., phenytoin, carbamazepine, rifampin, rifabutin, rifapentine, phenobarbital, and St. John's Wort) are not allowed for this study. Because the lists of these agents are constantly changing, frequently updated lists available at http://medicine.iupui.edu/clinpharm/ddis/table.asp or other reliable resources will be consulted. Patients who need to come off CYP3A4 inhibitors/inducers should adhere to a washout period of at least 5 times the half-life of the CYP3A4 inhibitors and 14 days of CYP3A4 inducers
* Patients with any other significant condition(s) that would make this protocol unreasonably hazardous are ineligible. Patients with uncontrolled intercurrent illness or clinical evidence of an active infection at the time of enrollment are ineligible
* Pregnant women are excluded from this study because cabozantinib is a receptor kinase inhibitor agent with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with cabozantinib in combination with nivolumab and ipilimumab, breastfeeding should be discontinued if the mother is treated with cabozantinib. These potential risks may also apply to other immunotherapeutic agents (ipilimumab and nivolumab) used in this study
* Patients with any of the following within 12 weeks prior to the first dose of cabozantinib: gastrointestinal bleeding, hemoptysis or pulmonary hemorrhage, radiographic evidence of cavitating pulmonary lesion(s), evidence of tumor invasion of the gastrointestinal (GI) tract (esophagus, stomach, small or large bowel, rectum, or anus), or any evidence of endotracheal or endobronchial tumor or encasement of any major blood vessels are ineligible
* The patient is unable to swallow tablets
* The patient has a corrected QT interval calculated by the Fridericia formula (QTcF) \>= 470 ms within 28 days before enrollment
* Patients with a requirement for steroid or immunosuppressive treatment should be excluded if they have a condition requiring systemic treatment with either corticosteroids (\> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids and adrenal replacement doses \> 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease

Contacts and Locations

Principal Investigator

A P Chen

PRINCIPAL_INVESTIGATOR

National Cancer Institute LAO

Study Locations (Sites)

City of Hope Comprehensive Cancer Center

Duarte, California, 91010

United States

UCI Health - Chao Family Comprehensive Cancer Center and Ambulatory Care

Irvine, California, 92612

United States

Keck Medicine of USC Koreatown

Los Angeles, California, 90020

United States

Los Angeles General Medical Center

Los Angeles, California, 90033

United States

USC / Norris Comprehensive Cancer Center

Los Angeles, California, 90033

United States

USC Norris Oncology/Hematology-Newport Beach

Newport Beach, California, 92663

United States

UC Irvine Health/Chao Family Comprehensive Cancer Center

Orange, California, 92868

United States

Smilow Cancer Hospital Care Center at Saint Francis

Hartford, Connecticut, 06105

United States

Yale University

New Haven, Connecticut, 06520

United States

Smilow Cancer Hospital Care Center-Trumbull

Trumbull, Connecticut, 06611

United States

MedStar Georgetown University Hospital

Washington D.C., District of Columbia, 20007

United States

University of Florida Health Science Center - Gainesville

Gainesville, Florida, 32610

United States

National Cancer Institute Developmental Therapeutics Clinic

Bethesda, Maryland, 20892

United States

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892

United States

Washington University School of Medicine

St Louis, Missouri, 63110

United States

Siteman Cancer Center-South County

St Louis, Missouri, 63129

United States

Laura and Isaac Perlmutter Cancer Center at NYU Langone

New York, New York, 10016

United States

UNC Lineberger Comprehensive Cancer Center

Chapel Hill, North Carolina, 27599

United States

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210

United States

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, 73104

United States

University of Pittsburgh Cancer Institute (UPCI)

Pittsburgh, Pennsylvania, 15232

United States

Vanderbilt University/Ingram Cancer Center

Nashville, Tennessee, 37232

United States

M D Anderson Cancer Center

Houston, Texas, 77030

United States

Huntsman Cancer Institute/University of Utah

Salt Lake City, Utah, 84112

United States

University of Virginia Cancer Center

Charlottesville, Virginia, 22908

United States

VCU Massey Comprehensive Cancer Center

Richmond, Virginia, 23298

United States

Collaborators and Investigators

Sponsor: National Cancer Institute LAO

A P Chen, PRINCIPAL_INVESTIGATOR, National Cancer Institute LAO

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2023-10-25

Study Completion Date2026-05-15

Study Record Updates

Study Start Date2023-10-25

Study Completion Date2026-05-15

Terms related to this study

Additional Relevant MeSH Terms

Locally Advanced Extraskeletal Myxoid Chondrosarcoma
Locally Advanced Leiomyosarcoma
Locally Advanced Liposarcoma
Locally Advanced Undifferentiated Pleomorphic Sarcoma
Locally Advanced Unresectable Soft Tissue Sarcoma
Metastatic Soft Tissue Sarcoma
Metastatic Undifferentiated Pleomorphic Sarcoma
Unresectable Leiomyosarcoma
Unresectable Liposarcoma
Unresectable Undifferentiated Pleomorphic Sarcoma