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NCT05836571Active, not recruitingPhase 2

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

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

Source: ClinicalTrials.gov · Last updated 9 Oct 2026

Brief summary (registry, in English)

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.

Status (registry)
Active, not recruiting
Phase (registry)
Phase 2
Study type
Interventional
Enrollment
66 (estimated)
First submitted
25 Apr 2023
Start date
25 Oct 2023
Primary completion date
15 May 2028
Lead sponsor
National Cancer Institute LAO
Diseases
Sarcoma
NCT number
NCT05836571

What you commit to

  • Study type: Interventional · Phase 2
  • Planned participants: 66
  • From 25 Oct 2023 to the primary completion date, 15 May 2028
  • 27 sites in 2 countries
  • Visits and tests: ask the trial team, the registry does not list them

Built from the registry fields of ClinicalTrials.gov. It describes the study, not your situation.

Who cannot take part

Copied verbatim from ClinicalTrials.gov and grouped by topic. Only the trial team decides who can take part.

Prior treatment

  • 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
  • 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
  • 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
  • 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

Other illness

  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to cabozantinib, nivolumab, or ipilimumab
  • 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

Lab values

  • The patient has a corrected QT interval calculated by the Fridericia formula (QTcF) \>= 470 ms within 28 days before enrollment

Other

  • The patient is unable to swallow tablets

Who the study is looking for

  • 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

Age in the registry: 18 years to - · Sex: All · Does not accept healthy volunteers

Full criteria on ClinicalTrials.gov

Sites (27)

Sites in registry order. Pick your city on the disease page to sort them by distance.

SiteCityCountrySite status
University Health Network, Princess Margaret Hospital
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TorontoCanadaUnknown status
National Cancer Institute Developmental Therapeutics Clinic
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BethesdaUnited StatesUnknown status
National Institutes of Health Clinical Center
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BethesdaUnited StatesUnknown status
UNC Lineberger Comprehensive Cancer Center
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Chapel HillUnited StatesUnknown status
University of Virginia Cancer Center
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CharlottesvilleUnited StatesUnknown status
Ohio State University Comprehensive Cancer Center
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ColumbusUnited StatesUnknown status
City of Hope Comprehensive Cancer Center
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DuarteUnited StatesUnknown status
UF Health Cancer Institute - Gainesville
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GainesvilleUnited StatesUnknown status
Smilow Cancer Hospital Care Center at Saint Francis
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HartfordUnited StatesUnknown status
UT MD Anderson Cancer Center
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HoustonUnited StatesUnknown status
UCI Health - Chao Family Comprehensive Cancer Center and Ambulatory Care
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IrvineUnited StatesUnknown status
Los Angeles General Medical Center
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Los AngelesUnited StatesUnknown status
Keck Medicine of USC Koreatown
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Los AngelesUnited StatesUnknown status
USC / Norris Comprehensive Cancer Center
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Los AngelesUnited StatesUnknown status
Vanderbilt University/Ingram Cancer Center
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NashvilleUnited StatesUnknown status
Yale University
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New HavenUnited StatesUnknown status
USC Norris Oncology/Hematology-Newport Beach
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Newport BeachUnited StatesUnknown status
Laura and Isaac Perlmutter Cancer Center at NYU Langone
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New YorkUnited StatesUnknown status
University of Oklahoma Health Sciences Center
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Oklahoma CityUnited StatesUnknown status
UC Irvine Health- Chao Family Comprehensive Cancer Center
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OrangeUnited StatesUnknown status
UPMC Hillman Cancer Center
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PittsburghUnited StatesUnknown status
VCU Massey Comprehensive Cancer Center
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RichmondUnited StatesUnknown status
Huntsman Cancer Institute/University of Utah
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Salt Lake CityUnited StatesUnknown status
Siteman Cancer Center-South County
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St LouisUnited StatesUnknown status
Washington University School of Medicine
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St LouisUnited StatesUnknown status
Smilow Cancer Hospital Care Center-Trumbull
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TrumbullUnited StatesUnknown status
MedStar Georgetown University Hospital
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Washington D.C.United StatesUnknown status

This page is information, not medical advice. Discuss any trial with your doctor.