Trial Title:
Testing Ipilimumab and Nivolumab Combination With or Without Cabozantinib in People >= 18 Years Old With Advanced Soft Tissue Sarcoma
NCT ID:
NCT05836571
Condition:
Locally Advanced Extraskeletal Myxoid Chondrosarcoma
Locally Advanced Leiomyosarcoma
Locally Advanced Liposarcoma
Locally Advanced Undifferentiated Pleomorphic Sarcoma
Locally Advanced Unresectable Soft Tissue Sarcoma
Metastatic Undifferentiated Pleomorphic Sarcoma
Conditions: Official terms:
Sarcoma
Leiomyosarcoma
Liposarcoma
Chondrosarcoma
Histiocytoma, Malignant Fibrous
Nivolumab
Ipilimumab
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Procedure
Intervention name:
Biopsy
Description:
Undergo biopsy
Arm group label:
Arm A (nivolumab, ipilimumab)
Arm group label:
Arm B (cabozantinib, nivolumab, ipilimumab)
Other name:
BIOPSY_TYPE
Other name:
Bx
Intervention type:
Procedure
Intervention name:
Biospecimen Collection
Description:
Undergo collection of blood
Arm group label:
Arm A (nivolumab, ipilimumab)
Arm group label:
Arm B (cabozantinib, nivolumab, ipilimumab)
Other name:
Biological Sample Collection
Other name:
Biospecimen Collected
Other name:
Specimen Collection
Intervention type:
Drug
Intervention name:
Cabozantinib
Description:
Given PO
Arm group label:
Arm B (cabozantinib, nivolumab, ipilimumab)
Intervention type:
Procedure
Intervention name:
Computed Tomography
Description:
Undergo CT
Arm group label:
Arm A (nivolumab, ipilimumab)
Arm group label:
Arm B (cabozantinib, nivolumab, ipilimumab)
Other name:
CAT
Other name:
CAT Scan
Other name:
Computed Axial Tomography
Other name:
Computerized Axial Tomography
Other name:
Computerized axial tomography (procedure)
Other name:
Computerized Tomography
Other name:
Computerized Tomography (CT) scan
Other name:
CT
Other name:
CT Scan
Other name:
tomography
Intervention type:
Biological
Intervention name:
Ipilimumab
Description:
Given IV
Arm group label:
Arm A (nivolumab, ipilimumab)
Arm group label:
Arm B (cabozantinib, nivolumab, ipilimumab)
Other name:
Anti-Cytotoxic T-Lymphocyte-Associated Antigen-4 Monoclonal Antibody
Other name:
BMS 734016
Other name:
BMS-734016
Other name:
BMS734016
Other name:
Ipilimumab Biosimilar CS1002
Other name:
MDX 010
Other name:
MDX-010
Other name:
MDX-CTLA4
Other name:
MDX010
Other name:
Yervoy
Intervention type:
Procedure
Intervention name:
Magnetic Resonance Imaging
Description:
Undergo MRI
Arm group label:
Arm A (nivolumab, ipilimumab)
Arm group label:
Arm B (cabozantinib, nivolumab, ipilimumab)
Other name:
Magnetic Resonance
Other name:
Magnetic Resonance Imaging (MRI)
Other name:
Magnetic resonance imaging (procedure)
Other name:
Magnetic Resonance Imaging Scan
Other name:
Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance
Other name:
MR
Other name:
MR Imaging
Other name:
MRI
Other name:
MRI Scan
Other name:
MRIs
Other name:
NMR Imaging
Other name:
NMRI
Other name:
Nuclear Magnetic Resonance Imaging
Other name:
sMRI
Other name:
Structural MRI
Intervention type:
Biological
Intervention name:
Nivolumab
Description:
Given IV
Arm group label:
Arm A (nivolumab, ipilimumab)
Arm group label:
Arm B (cabozantinib, nivolumab, ipilimumab)
Other name:
ABP 206
Other name:
BCD-263
Other name:
BMS 936558
Other name:
BMS-936558
Other name:
BMS936558
Other name:
CMAB819
Other name:
MDX 1106
Other name:
MDX-1106
Other name:
MDX1106
Other name:
NIVO
Other name:
Nivolumab Biosimilar ABP 206
Other name:
Nivolumab Biosimilar BCD-263
Other name:
Nivolumab Biosimilar CMAB819
Other name:
ONO 4538
Other name:
ONO-4538
Other name:
ONO4538
Other name:
Opdivo
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.
Criteria for 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
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
City of Hope Comprehensive Cancer Center
Address:
City:
Duarte
Zip:
91010
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
800-826-4673
Email:
becomingapatient@coh.org
Investigator:
Last name:
Adam Rock
Email:
Principal Investigator
Facility:
Name:
UCI Health - Chao Family Comprehensive Cancer Center and Ambulatory Care
Address:
City:
Irvine
Zip:
92612
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
877-827-8839
Email:
ucstudy@uci.edu
Investigator:
Last name:
Warren A. Chow
Email:
Principal Investigator
Facility:
Name:
Keck Medicine of USC Koreatown
Address:
City:
Los Angeles
Zip:
90020
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
213-388-0908
Investigator:
Last name:
James S. Hu
Email:
Principal Investigator
Facility:
Name:
Los Angeles General Medical Center
Address:
City:
Los Angeles
Zip:
90033
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
323-865-0451
Email:
uscnorrisinfo@med.usc.edu
Investigator:
Last name:
James S. Hu
Email:
Principal Investigator
Facility:
Name:
USC / Norris Comprehensive Cancer Center
Address:
City:
Los Angeles
Zip:
90033
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
323-865-0451
Investigator:
Last name:
James S. Hu
Email:
Principal Investigator
Facility:
Name:
USC Norris Oncology/Hematology-Newport Beach
Address:
City:
Newport Beach
Zip:
92663
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
323-865-0451
Investigator:
Last name:
James S. Hu
Email:
Principal Investigator
Facility:
Name:
UC Irvine Health/Chao Family Comprehensive Cancer Center
Address:
City:
Orange
Zip:
92868
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
877-827-8839
Email:
ucstudy@uci.edu
Investigator:
Last name:
Warren A. Chow
Email:
Principal Investigator
Facility:
Name:
Smilow Cancer Hospital Care Center at Saint Francis
Address:
City:
Hartford
Zip:
06105
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
203-785-5702
Email:
canceranswers@yale.edu
Investigator:
Last name:
Hari A. Deshpande
Email:
Principal Investigator
Facility:
Name:
Yale University
Address:
City:
New Haven
Zip:
06520
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
203-785-5702
Email:
canceranswers@yale.edu
Investigator:
Last name:
Hari A. Deshpande
Email:
Principal Investigator
Facility:
Name:
Smilow Cancer Hospital Care Center-Trumbull
Address:
City:
Trumbull
Zip:
06611
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
203-785-5702
Email:
canceranswers@yale.edu
Investigator:
Last name:
Hari A. Deshpande
Email:
Principal Investigator
Facility:
Name:
MedStar Georgetown University Hospital
Address:
City:
Washington
Zip:
20007
Country:
United States
Status:
Suspended
Facility:
Name:
University of Florida Health Science Center - Gainesville
Address:
City:
Gainesville
Zip:
32610
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
352-273-8010
Email:
cancer-center@ufl.edu
Investigator:
Last name:
Thomas J. George
Email:
Principal Investigator
Facility:
Name:
National Cancer Institute Developmental Therapeutics Clinic
Address:
City:
Bethesda
Zip:
20892
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
800-411-1222
Investigator:
Last name:
A P. Chen
Email:
Principal Investigator
Facility:
Name:
National Institutes of Health Clinical Center
Address:
City:
Bethesda
Zip:
20892
Country:
United States
Status:
Active, not recruiting
Facility:
Name:
Washington University School of Medicine
Address:
City:
Saint Louis
Zip:
63110
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
800-600-3606
Email:
info@siteman.wustl.edu
Investigator:
Last name:
Mia C. Weiss
Email:
Principal Investigator
Facility:
Name:
Siteman Cancer Center-South County
Address:
City:
Saint Louis
Zip:
63129
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
800-600-3606
Email:
info@siteman.wustl.edu
Investigator:
Last name:
Mia C. Weiss
Email:
Principal Investigator
Facility:
Name:
Ohio State University Comprehensive Cancer Center
Address:
City:
Columbus
Zip:
43210
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
800-293-5066
Email:
Jamesline@osumc.edu
Investigator:
Last name:
Gabriel R. Tinoco Suarez
Email:
Principal Investigator
Facility:
Name:
University of Oklahoma Health Sciences Center
Address:
City:
Oklahoma City
Zip:
73104
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
405-271-8777
Email:
ou-clinical-trials@ouhsc.edu
Investigator:
Last name:
Minh Phan
Email:
Principal Investigator
Facility:
Name:
University of Pittsburgh Cancer Institute (UPCI)
Address:
City:
Pittsburgh
Zip:
15232
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
412-647-8073
Investigator:
Last name:
Melissa A. Burgess
Email:
Principal Investigator
Facility:
Name:
M D Anderson Cancer Center
Address:
City:
Houston
Zip:
77030
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
877-632-6789
Email:
askmdanderson@mdanderson.org
Investigator:
Last name:
Elise F. Nassif
Email:
Principal Investigator
Facility:
Name:
Huntsman Cancer Institute/University of Utah
Address:
City:
Salt Lake City
Zip:
84112
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
888-424-2100
Email:
cancerinfo@hci.utah.edu
Investigator:
Last name:
Anna Chalmers
Email:
Principal Investigator
Facility:
Name:
Virginia Commonwealth University/Massey Cancer Center
Address:
City:
Richmond
Zip:
23298
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Email:
CTOclinops@vcu.edu
Investigator:
Last name:
Andrew Poklepovic
Email:
Principal Investigator
Facility:
Name:
University Health Network-Princess Margaret Hospital
Address:
City:
Toronto
Zip:
M5G 2M9
Country:
Canada
Status:
Active, not recruiting
Start date:
October 25, 2023
Completion date:
May 15, 2026
Lead sponsor:
Agency:
National Cancer Institute (NCI)
Agency class:
NIH
Source:
National Cancer Institute (NCI)
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05836571
