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

Primary Purpose

Extraskeletal Myxoid Chondrosarcoma, Leiomyosarcoma, Liposarcoma

Status
Recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Biopsy
Biospecimen Collection
Cabozantinib
Computed Tomography
Ipilimumab
Magnetic Resonance Imaging
Nivolumab
Sponsored by
National Cancer Institute (NCI)
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Extraskeletal Myxoid Chondrosarcoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion 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 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 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 Exclusion Criteria: 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 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 that require concomitant treatment, in therapeutic doses, with anticoagulants such as warfarin or warfarin-related agents, heparin, thrombin or Factor Xa inhibitors, or antiplatelet agents (e.g., clopidogrel). Low dose aspirin (=< 81 mg/day), low-dose warfarin (=< 1 mg/day), and prophylactic low molecular weight heparin (LMWH) are permitted. (Please note that there may be cases in which patients on study require anticoagulation for deep vein thrombosis/pulmonary embolism [DVT/PE] management; this does not necessitate taking the patient off 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 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

Sites / Locations

  • National Cancer Institute Developmental Therapeutics ClinicRecruiting
  • National Institutes of Health Clinical CenterRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

Arm A (nivolumab, ipilimumab)

Arm B (cabozantinib, nivolumab, ipilimumab)

Arm Description

Patients receive nivolumab IV over 30 minutes and ipilimumab IV over 30-60 minutes on day 1 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity for 4 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive nivolumab IV on day 1 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT or MRI scans throughout the trial, tumor biopsies on study, and collection of blood throughout the trial.

Patients receive cabozantinib PO 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 in the absence of disease progression or unacceptable toxicity. Patients then receive nivolumab IV on day 1 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT or MRI scans throughout the trial, tumor biopsies on study, and collection of blood throughout the trial.

Outcomes

Primary Outcome Measures

Progression-free survival (PFS)
Will be assessed using Response Evaluation Criteria in Solid Tumors version (v)1.1. The primary analysis will be a logrank test and will be performed once 52 PFS events have been observed. In addition, a single interim futility analysis (Wieand rule) will be performed at 50% information (26 PFS events).

Secondary Outcome Measures

Objective response rate
Defined as complete response or partial response by RECIST v1.1. Response rates within the two study arms will be (separately) reported and will be directly compared using a two-sample test of proportions. In addition, will report the rate of objective response to cabozantinib + ipilimumab + nivolumab triplet therapy in patients who have crossed over after their disease progressed on ipilimumab + nivolumab doublet.
Number of tumor-infiltrating CD8+ T cells
Will be evaluated in tumor biopsies before and after treatment. Changes between paired samples will be interpreted as being likely treatment-induced if they exceed the sampling, biological, and technical variabilities determined for the assay. Unpaired baseline and post-treatment measurements may also be assessed for correlation with response, which will shed light on possible CD8+ T cell density or infiltration requirements that could inform future trial designs.

Full Information

First Posted
April 25, 2023
Last Updated
October 21, 2023
Sponsor
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT05836571
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 Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
June 25, 2024 (Anticipated)
Primary Completion Date
May 15, 2026 (Anticipated)
Study Completion Date
May 15, 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Cancer Institute (NCI)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
This phase II trial compares the effect of ipilimumab and nivolumab combination with cabozantinib, ipilimumab, and nivolumab combination in treating patients >= 18 years old with soft tissue sarcoma that may have 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 a chemotherapy drug that works by blocking the formation of new blood vessels in tumors, something tumors need to do to grow. Adding cabozantinib to the combination of ipilimumab and nivolumab may be effective in slowing the growth of soft tissue sarcoma tumors.
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. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity for4 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive nivolumab IV on day 1 of each cycle. 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 throughout the trial, tumor biopsies on study, 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 in the absence of disease progression or unacceptable toxicity. Patients then receive nivolumab IV on day 1 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT or MRI scans throughout the trial, tumor biopsies on study, and collection of blood throughout the trial. Patients are followed for 30 days after completion of study treatment.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Extraskeletal Myxoid Chondrosarcoma, Leiomyosarcoma, Liposarcoma, Undifferentiated Pleomorphic Sarcoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
66 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Arm A (nivolumab, ipilimumab)
Arm Type
Active Comparator
Arm Description
Patients receive nivolumab IV over 30 minutes and ipilimumab IV over 30-60 minutes on day 1 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity for 4 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive nivolumab IV on day 1 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT or MRI scans throughout the trial, tumor biopsies on study, and collection of blood throughout the trial.
Arm Title
Arm B (cabozantinib, nivolumab, ipilimumab)
Arm Type
Experimental
Arm Description
Patients receive cabozantinib PO 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 in the absence of disease progression or unacceptable toxicity. Patients then receive nivolumab IV on day 1 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT or MRI scans throughout the trial, tumor biopsies on study, and collection of blood throughout the trial.
Intervention Type
Procedure
Intervention Name(s)
Biopsy
Other Intervention Name(s)
BIOPSY_TYPE, Bx
Intervention Description
Undergo biopsy
Intervention Type
Procedure
Intervention Name(s)
Biospecimen Collection
Other Intervention Name(s)
Biological Sample Collection, Biospecimen Collected, Specimen Collection
Intervention Description
Undergo collection of blood
Intervention Type
Drug
Intervention Name(s)
Cabozantinib
Intervention Description
Given PO
Intervention Type
Procedure
Intervention Name(s)
Computed Tomography
Other Intervention Name(s)
CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized axial tomography (procedure), Computerized Tomography, CT, CT Scan, tomography
Intervention Description
Undergo CT
Intervention Type
Biological
Intervention Name(s)
Ipilimumab
Other Intervention Name(s)
Anti-Cytotoxic T-Lymphocyte-Associated Antigen-4 Monoclonal Antibody, BMS-734016, Ipilimumab Biosimilar CS1002, MDX-010, MDX-CTLA4, Yervoy
Intervention Description
Given IV
Intervention Type
Procedure
Intervention Name(s)
Magnetic Resonance Imaging
Other Intervention Name(s)
Magnetic Resonance, Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan, Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance, MR, MR Imaging, MRI, MRI Scan, NMR Imaging, NMRI, Nuclear Magnetic Resonance Imaging
Intervention Description
Undergo MRI
Intervention Type
Biological
Intervention Name(s)
Nivolumab
Other Intervention Name(s)
ABP 206, BMS-936558, CMAB819, MDX-1106, NIVO, Nivolumab Biosimilar ABP 206, Nivolumab Biosimilar CMAB819, ONO-4538, Opdivo
Intervention Description
Given IV
Primary Outcome Measure Information:
Title
Progression-free survival (PFS)
Description
Will be assessed using Response Evaluation Criteria in Solid Tumors version (v)1.1. The primary analysis will be a logrank test and will be performed once 52 PFS events have been observed. In addition, a single interim futility analysis (Wieand rule) will be performed at 50% information (26 PFS events).
Time Frame
Up to 30 days after completion of study treatment
Secondary Outcome Measure Information:
Title
Objective response rate
Description
Defined as complete response or partial response by RECIST v1.1. Response rates within the two study arms will be (separately) reported and will be directly compared using a two-sample test of proportions. In addition, will report the rate of objective response to cabozantinib + ipilimumab + nivolumab triplet therapy in patients who have crossed over after their disease progressed on ipilimumab + nivolumab doublet.
Time Frame
Up to 30 days after completion of study treatment
Title
Number of tumor-infiltrating CD8+ T cells
Description
Will be evaluated in tumor biopsies before and after treatment. Changes between paired samples will be interpreted as being likely treatment-induced if they exceed the sampling, biological, and technical variabilities determined for the assay. Unpaired baseline and post-treatment measurements may also be assessed for correlation with response, which will shed light on possible CD8+ T cell density or infiltration requirements that could inform future trial designs.
Time Frame
Baseline and cycle 2, day 22 (C2D22)
Other Pre-specified Outcome Measures:
Title
Tumor-infiltrating CD3+ T cells and CD68+ macrophages
Description
Will be evaluated in tumor biopsies. Non-parametric analyses will be used.
Time Frame
Baseline and C2D22
Title
Genetic aberrations and/or tumor mutational burden
Description
Will investigate whether response is associated with genetic aberrations and/or tumor mutational burden. Non-parametric analyses will be used.
Time Frame
Up to 30 days after completion of study treatment
Title
T cell receptor signaling in tumor-infiltrating T cells
Description
Will be evaluated in tumor biopsies. Non-parametric analyses will be used.
Time Frame
Baseline and C2D22
Title
Total MET and activated MET
Description
Will be evaluated in biopsy specimens before and after study treatment. Will evaluate molecular target engagement by cabozantinib (as shown by a lower phosphorylated [p]MET/MET ratio). Non-parametric analyses will be used.
Time Frame
Baseline and C2D22

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion 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 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 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 Exclusion Criteria: 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 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 that require concomitant treatment, in therapeutic doses, with anticoagulants such as warfarin or warfarin-related agents, heparin, thrombin or Factor Xa inhibitors, or antiplatelet agents (e.g., clopidogrel). Low dose aspirin (=< 81 mg/day), low-dose warfarin (=< 1 mg/day), and prophylactic low molecular weight heparin (LMWH) are permitted. (Please note that there may be cases in which patients on study require anticoagulation for deep vein thrombosis/pulmonary embolism [DVT/PE] management; this does not necessitate taking the patient off 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 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
A P Chen
Organizational Affiliation
National Cancer Institute LAO
Official's Role
Principal Investigator
Facility Information:
Facility Name
National Cancer Institute Developmental Therapeutics Clinic
City
Bethesda
State/Province
Maryland
ZIP/Postal Code
20892
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Site Public Contact
Phone
800-411-1222
First Name & Middle Initial & Last Name & Degree
A P. Chen
Facility Name
National Institutes of Health Clinical Center
City
Bethesda
State/Province
Maryland
ZIP/Postal Code
20892
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Site Public Contact
Phone
800-411-1222
First Name & Middle Initial & Last Name & Degree
A P. Chen

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.
IPD Sharing URL
https://grants.nih.gov/policy/sharing.htm

Learn more about this trial

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

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