Cabozantinib S-malate and Nivolumab in Treating Patients With Advanced, Recurrent, or Metastatic Endometrial Cancer

NCT03367741 | Active Not Recruiting Phase 2 Results FDA Drug

• 4 other identifiers: NCI-2017-02211PHL-09910104UM1CA186644
• Study Type: interventional
• Target: 82
• Locations: 2 countries
• Sites: 34

Brief Summary

This randomized phase II trial studies how well cabozantinib s-malate and nivolumab work in treating patients with endometrial cancer that has come back (recurrent) or spread to other places in the body (advanced or metastatic). Cabozantinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving cabozantinib and nivolumab may work better in treating endometrial cancer.

Conditions

Advanced Endometrial Carcinoma; Recurrent Endometrial Carcinoma; Stage III Uterine Corpus Carcinoma or Carcinosarcoma AJCC v8; Stage IV Uterine Corpus Carcinoma or Carcinosarcoma AJCC v8; Metastatic Endometrial Carcinoma

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival (PFS)

  PFS is defined as the interval between randomization and disease progression or death from any cause, which ever occurred earlier.

  Up to 1 year

Secondary Outcomes (4)

• Overall Response Rate (ORR)

  Up to 1 year

• Overall Survival (OS)

  Up to 4 years

• Incidence of Adverse Events

  Up to 1 year

• PD-L1 Expression, CD3, CD4 and CD8 Analysis

  Up to 1 year

Study Arms (2)

Arm A (cabozantinib s-malate, nivolumab)

EXPERIMENTAL

Patients receive cabozantinib s-malate PO QD on days 1-28 and nivolumab IV over 30 minutes on days 1 and 15, then on day 1 beginning cycle 5. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo CT scan, MRI, and blood sample collection throughout the study and undergo biopsy at screening and optionally at follow up.

Procedure: Biopsy Procedure; Procedure: Biospecimen Collection; Drug: Cabozantinib S-malate; Procedure: Computed Tomography; Procedure: Magnetic Resonance Imaging; Biological: Nivolumab

Arm B (nivolumab)

EXPERIMENTAL

Patients receive nivolumab as in Arm A. Patients may cross-over to Arm A at the time of disease progression. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo CT scan, MRI, and blood sample collection throughout the study and undergo biopsy at screening and optionally at follow up.

Procedure: Biopsy Procedure; Procedure: Biospecimen Collection; Procedure: Computed Tomography; Procedure: Magnetic Resonance Imaging; Biological: Nivolumab

Interventions

Biopsy Procedure PROCEDURE

Undergo tumor biopsy

Also known as: Biopsy, BIOPSY_TYPE, Bx

Arm A (cabozantinib s-malate, nivolumab); Arm B (nivolumab)

Biospecimen Collection PROCEDURE

Undergo blood sample collection

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Arm A (cabozantinib s-malate, nivolumab); Arm B (nivolumab)

Cabozantinib S-malate DRUG

Given PO

Also known as: BMS-907351, Cabometyx, Cometriq, XL 184, XL-184, XL184

Arm A (cabozantinib s-malate, nivolumab)

Computed Tomography PROCEDURE

Undergo CT scan

Also known as: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized axial tomography (procedure), Computerized Tomography, Computerized Tomography (CT) scan, CT, CT Scan, tomography

Arm A (cabozantinib s-malate, nivolumab); Arm B (nivolumab)

Magnetic Resonance Imaging PROCEDURE

Undergo MRI

Also known as: Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan, Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance, MR, MR Imaging, MRI, MRI Scan, MRIs, NMR Imaging, NMRI, Nuclear Magnetic Resonance Imaging, sMRI, Structural MRI

Arm A (cabozantinib s-malate, nivolumab); Arm B (nivolumab)

Nivolumab BIOLOGICAL

Given IV

Also known as: ABP 206, BCD-263, BMS 936558, BMS-936558, BMS936558, CMAB819, MDX 1106, MDX-1106, MDX1106, NIVO, Nivolumab Biosimilar ABP 206, Nivolumab Biosimilar BCD-263, Nivolumab Biosimilar CMAB819, ONO 4538, ONO-4538, ONO4538, Opdivo

Arm A (cabozantinib s-malate, nivolumab); Arm B (nivolumab)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have histologically or cytologically confirmed epithelial endometrial carcinoma; all histologies are accepted; patients with diagnosis of endometrial carcinosarcoma will be enrolled in the exploratory cohort (arm C) and will receive combination of cabozantinib and nivolumab
• Patients must have advance, recurrent or metastatic endometrial cancer
• Patients must have radiological evidence of disease progression following the most recent treatment
• Patients must have measurable disease according Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1 criteria
• Must have MS/MMR result available at time of registration; MS/MMR status is to be determined per local practice (i.e. immunohistochemistry \[IHC\], polymerase chain reaction \[PCR\], or other methods)
• Prior therapy: eligible subjects must have had at least one line of platinum-based chemotherapy; this may be adjuvant therapy or first line of cytotoxic therapy for metastatic disease; prior hormonal therapy for metastatic/recurrent disease, prior targeted therapy, and prior radiotherapy are allowed; no maximum number of previous lines of chemotherapies; concomitant chemo-radiation is not considered as previous line of systemic chemotherapy
• Availability of archival tissue for correlative analysis
• Age \>=18 years. Because no dosing or adverse event data are currently available on the use of cabozantinib and nivolumab in patients \< 18 years of age, children are excluded from this study, but will be eligible for future pediatric trials
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2
• Absolute neutrophil count \>= 1,500/mcL
• Platelets \>= 100 x 10\^9/L
• Total bilirubin =\< 1.5 ULN (upper limit of normal), unless due to Gilbert's syndrome
• Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 3 x institutional upper limit of normal
• Creatinine =\< 1.5 ULN OR creatinine clearance \>= 50 mL/min/1.73 m\^2 for patients with creatinine levels above institutional normal
• Serum albumin \>= 28 g/L

You may not qualify if:

• Patients who have had chemotherapy (including investigational cytotoxic chemotherapy), biologic agents (e.g. targeted therapy or antibodies) or radiotherapy within 4 weeks prior to the first dose of study treatment
• Patients who have not recovered from adverse events attributed to prior anti-cancer therapy (i.e. have residual toxicities \> grade 1, except for alopecia, neuropathy, lymphocytopenia and other non-clinically significant adverse events)
• Patients who are receiving any other investigational agents
• Patients should be excluded if they have had prior treatment with anti-CTLA-4 antibody or any other antibody or drug specifically targeting T-cell co-stimulation; previous treatment with anti-PD-1, anti-PD-L1 or anti-PD-L2 is allowed and patients will be enrolled in the exploratory cohort (arm C) at the time of progression from last line of treatment (treatment with immune check point inhibitor does not have to necessary be the last line of treatment)
• Patients should be excluded if they have had prior treatment with cabozantinib; previous use of other antiangiogenic agents other than cabozantinib is allowed
• Any other active malignancy other than the endometrial cancer, that is progressing or requiring active treatment with the exception of basal or squamous cell skin cancer, superficial bladder cancer, carcinoma in situ of any site
• Patients with known brain metastases should be excluded from this clinical trial because of their poor prognosis and because of the possible increased risk of bleeding if treatment with antiangiogenic agents is provided; patients with history of brain metastases can enroll provided the brain metastases were removed and controlled with no radiological evidence within the past 6 months
• Patients requiring concomitant treatment, in therapeutic doses, with anticoagulants such as warfarin or warfarin-related agents, heparin, thrombin or factor Xa inhibitors, antiplatelet agents (e.g. clopidogrel) or new oral anticoagulants; low-dose aspirin (=\< 81 mg/day), and prophylactic low molecular weight heparin (LMWH) are permitted
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to cabozantinib or nivolumab
• Patients require chronic concomitant treatment of strong CYP450 3A4 inducers (e.g. dexamethasone, phenytoin, carbamazepine, rifampicin, rifabutin, rifapentine, phenobarbital, St. John's wort) or inhibitors (e.g. ketoconazole, miconazole, itraconazole, voriconazole, posaconazole, clarithromycin, telithromycin, indinavir, saquinavir, ritonavir, nelfinavir, amprenavir, fosamprenavir nefazodone, lopinavir, troleandomycin, mibefradil and conivaptan); because the lists of these agents are constantly changing, it is important to regularly consult a frequently-updated list, medical reference texts such as the Physicians' Desk Reference may also provide this information; as part of the enrollment/informed consent procedures, the patient will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the patient is considering a new over-the-counter medicine or herbal product
• The subject has experienced any of the following:
• Clinically-significant gastrointestinal bleeding within 6 months before the first dose of study treatment;
• Hemoptysis of \>= 0.5 teaspoon (2.5 mL) of red blood within 3 months before the first dose of study treatment;
• Any other signs indicative of hemorrhage within 3 months before the first dose of study treatment
• The subject has radiographic evidence of cavitating pulmonary lesion(s)

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (34)

Mayo Clinic Hospital in Arizona

Phoenix, Arizona, 85054, United States

Location

Mayo Clinic in Arizona

Scottsdale, Arizona, 85259, United States

Location

City of Hope Comprehensive Cancer Center

Duarte, California, 91010, United States

Location

UC San Diego Moores Cancer Center

La Jolla, California, 92093, United States

Location

Los Angeles General Medical Center

Los Angeles, California, 90033, United States

Location

USC / Norris Comprehensive Cancer Center

Los Angeles, California, 90033, United States

Location

University of California Davis Comprehensive Cancer Center

Sacramento, California, 95817, United States

Location

University of Florida Health Science Center - Gainesville

Gainesville, Florida, 32610, United States

Location

Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

Northwestern University

Chicago, Illinois, 60611, United States

Location

University of Chicago Comprehensive Cancer Center

Chicago, Illinois, 60637, United States

Location

UC Comprehensive Cancer Center at Silver Cross

New Lenox, Illinois, 60451, United States

Location

University of Chicago Medicine-Orland Park

Orland Park, Illinois, 60462, United States

Location

University of Kansas Clinical Research Center

Fairway, Kansas, 66205, United States

Location

Johns Hopkins University/Sidney Kimmel Cancer Center

Baltimore, Maryland, 21287, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Mayo Clinic in Rochester

Rochester, Minnesota, 55905, United States

Location

Siteman Cancer Center at Saint Peters Hospital

City of Saint Peters, Missouri, 63376, United States

Location

Siteman Cancer Center at West County Hospital

Creve Coeur, Missouri, 63141, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Siteman Cancer Center-South County

St Louis, Missouri, 63129, United States

Location

Siteman Cancer Center at Christian Hospital

St Louis, Missouri, 63136, United States

Location

Rutgers Cancer Institute of New Jersey

New Brunswick, New Jersey, 08903, United States

Location

Laura and Isaac Perlmutter Cancer Center at NYU Langone

New York, New York, 10016, United States

Location

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

Location

Thomas Jefferson University Hospital

Philadelphia, Pennsylvania, 19107, United States

Location

University of Pittsburgh Cancer Institute (UPCI)

Pittsburgh, Pennsylvania, 15232, United States

Location

Parkland Memorial Hospital

Dallas, Texas, 75235, United States

Location

UT Southwestern/Simmons Cancer Center-Dallas

Dallas, Texas, 75390, United States

Location

Huntsman Cancer Institute/University of Utah

Salt Lake City, Utah, 84112, United States

Location

University of Virginia Cancer Center

Charlottesville, Virginia, 22908, United States

Location

VCU Massey Comprehensive Cancer Center

Richmond, Virginia, 23298, United States

Location

University of Wisconsin Carbone Cancer Center - University Hospital

Madison, Wisconsin, 53792, United States

Location

University Health Network-Princess Margaret Hospital

Toronto, Ontario, M5G 2M9, Canada

Location

Related Publications (1)

• Lheureux S, Matei DE, Konstantinopoulos PA, Wang BX, Gadalla R, Block MS, Jewell A, Gaillard SL, McHale M, McCourt C, Temkin S, Girda E, Backes FJ, Werner TL, Duska L, Kehoe S, Colombo I, Wang L, Li X, Wildman R, Soleimani S, Lien S, Wright J, Pugh T, Ohashi PS, Brooks DG, Fleming GF. Translational randomized phase II trial of cabozantinib in combination with nivolumab in advanced, recurrent, or metastatic endometrial cancer. J Immunother Cancer. 2022 Mar;10(3):e004233. doi: 10.1136/jitc-2021-004233.

  PMID: 35288469 DERIVED

MeSH Terms

Conditions

Endometrial Neoplasms; Carcinosarcoma

Interventions

Biopsy; Specimen Handling; cabozantinib; Magnetic Resonance Spectroscopy; Nivolumab

Condition Hierarchy (Ancestors)

Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Neoplasms, Complex and Mixed; Neoplasms by Histologic Type; Sarcoma; Neoplasms, Connective and Soft Tissue

Intervention Hierarchy (Ancestors)

Cytodiagnosis; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; Investigative Techniques; Spectrum Analysis; Chemistry Techniques, Analytical; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Dr. Stephanie Lheureux
• Organization: University Health Network- Princess Margaret Cancer Centre

Stephanie.Lheureux@uhn.ca

416-946-2818

Study Officials

• Stephanie Lheureux

  University Health Network Princess Margaret Cancer Center LAO

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 8, 2017
• First Posted: December 11, 2017
• Study Start: April 16, 2018
• Primary Completion: May 9, 2025
• Study Completion (Estimated): July 23, 2026
• Last Updated: April 29, 2026
• Results First Posted: April 29, 2026

Record last verified: 2026-03

Locations

US (33); CA (1)