Cabozantinib S-Malate in Treating Patients With Recurrent or Metastatic Endometrial Cancer

Completed · Phase 2

Conditions studied: Endometrial Adenosquamous Carcinoma, Endometrial Clear Cell Adenocarcinoma, Endometrial Mixed Cell Adenocarcinoma, Endometrial Serous Adenocarcinoma, Metastatic Endometrioid Adenocarcinoma, Recurrent Malignant Uterine Corpus Neoplasm, Stage IV Uterine Corpus Carcinoma or Carcinosarcoma by AJCC v7 Stage, Stage IVA Uterine Corpus Carcinoma or Carcinosarcoma by AJCC v7 Stage, Stage IVB Uterine Corpus Carcinoma or Carcinosarcoma by AJCC v7 Stage, Uterine Corpus Carcinosarcoma

In brief

This phase II trial studies how well cabozantinib s-malate works in treating patients with endometrial cancer that has come back (recurrent) or has spread to other places in the body (metastatic). Cabozantinib s-malate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor.

Key facts

Study ID

NCT01935934

Run by

National Cancer Institute (NCI)

People needed

102

Starts

2013-05-08

Expected to finish

2024-10-24

Last updated by the study team

2025-10-01

Who can join

Age: 18 and older. Sex: female. Healthy volunteers: not accepted.

You may qualify if…

• Patients must have histologically or cytologically confirmed metastatic endometrial cancer; eligible histologies for the experimental cohort are: endometrioid or serous; eligible histologies for the exploratory cohort are: carcinosarcoma, clear cell, mixed, adenosquamous and any other rare sub-type of endometrial cancer
• 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 >= 10 mm with computed tomography (CT) scan, magnetic resonance imaging (MRI), or calipers by clinical exam and >= 15 mm in short axis for nodal lesions; patients must have radiographic evidence of disease progression following the most recent line of treatment
• Prior therapy: Eligible subjects must have had 1 line of systemic cytotoxic treatment; this may be adjuvant therapy with documented progression within 12 months of completion, or 1 line of cytotoxic therapy for metastatic disease; NOTE: eligible patients are allowed up to 2 lines of systemic cytotoxic treatment, of which only 1 line is allowed for metastatic disease; the acceptance of progression within 12 months of adjuvant is part inclusion to not require patient to re-challenge with chemotherapy (chemo) if they progressed soon after adjuvant therapy; prior hormonal therapy for metastatic/recurrent disease is also allowed; prior targeted therapy not directed against cMET or vascular endothelial growth factor (VEGF) pathways is allowed
• Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%)
• Life expectancy of greater than 3 months
• Absolute neutrophil count >= 1.5 x 10\^9/L
• Platelets >= 100 x 10\^9/L
• Total bilirubin =< 1.5 x upper limit of normal (ULN)
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 3.0 X institutional upper limit of normal
• Creatinine =< 1.5 x ULN OR creatinine clearance >= 50 mL/min/1.73 m\^2 for patients with creatinine levels above institutional normal
• Hemoglobin >= 90 g/L
• Serum albumin >= 28 g/L
• Lipase < 2.0 x ULN; no radiologic/clinical evidence of pancreatitis
• Urine protein/creatinine ratio (UPCR) =< 1
• Serum phosphorus, calcium, magnesium and potassium >= lower limit of normal (LLN)
• Women of childbearing potential must have a negative pregnancy test at screening; women of childbearing potential include women who have experienced menarche and who have not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or are not postmenopausal; postmenopausal is defined as amenorrhea >= 12 consecutive months; note: women who have been amenorrheic for 12 or more months are still considered to be of childbearing potential if the amenorrhea is possibly due to prior chemotherapy, antiestrogens, ovarian suppression or any other reversible reason
• Women of child-bearing potential must agree to use adequate contraception prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while she is participating in this study, she should inform her treating physician immediately; sexually active subjects must agree to use medically accepted barrier methods of contraception (e.g., male or female condom) during the course of the study and for 4 months after the last dose of study drug(s), even if oral contraceptives are also used; all subjects of reproductive potential must agree to use both a barrier method and a second method of birth control during the course of the study and for 4 months after the last dose of study drug(s)
• Patients must consent to analysis on archival tissue; if archival sample is not available, a sufficient tumor biopsy can be performed a minimum of 28 days prior to start of treatment if felt to be clinically reasonable
• Ability to understand and the willingness to sign a written informed consent document

You may not qualify if…

• Patients who have had chemotherapy (including investigational cytotoxic chemotherapy), biologic agents (e.g., cytokines or antibodies) or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) before the first dose of study treatment or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier
• Prior treatment with cabozantinib
• The subject has received radiation therapy:
• To bone metastasis within 14 days before the first dose of study treatment
• To any other site(s) within 28 days before the first dose of study treatment
• The subject has received radionuclide treatment within 6 weeks of the first dose of study treatment
• The subject has received prior treatment with a small molecule kinase inhibitor or a hormonal therapy (including investigational kinase inhibitors or hormones) within 14 days or five half-lives of the compound or active metabolites, whichever is longer, before the first dose of study treatment
• The subject has received any other type of investigational agent within 28 days before the first dose of study treatment
• The subject has not recovered to baseline or Common Terminology Criteria for Adverse Events (CTCAE) =< grade 1 from related toxicity to all prior therapies except alopecia and other non-clinically significant adverse events (AEs)
• Any other prior malignancy from which the patient has been disease free for less than 3 years, with the exception of adequately treated and cured basal or squamous cell skin cancer, superficial bladder cancer, carcinoma in situ of any site or any other cancer
• Patients with known brain metastases should be excluded from this clinical trial
• The subject has prothrombin time (PT)/international normalized ratio (INR) or partial thromboplastin time (PTT) test >= 1.3 x the laboratory ULN =< 7 days before the first dose of study treatment
• Therapeutic anticoagulation with warfarin, antiplatelet agents (e.g., clopidogrel), thrombin, or Factor Xa inhibitors is not allowed; therapeutic anticoagulation with low molecular weight heparin (LMWH) is allowed as well as prophylactic anticoagulation using low dose aspirin (=< 81 mg/day), low-dose warfarin (=< 1 mg/day), and LMWH
• The subject requires chronic concomitant treatment of strong CYP3A4 inducers (e.g., dexamethasone, phenytoin, carbamazepine, rifampin, rifabutin, rifapentine, phenobarbital, and St. John's wort)
• 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 pulmonary hemorrhage within 3 months before the first dose of study treatment
• The subject has tumor in contact with, invading or encasing any major blood vessels
• The subject has evidence of tumor invading the gastrointestinal (GI) tract (esophagus, stomach, small or large bowel, rectum or anus), or any evidence of endotracheal or endobronchial tumor within 28 days before the first dose of cabozantinib
• The subject has uncontrolled, significant intercurrent or recent illness including, but not limited to, the following conditions:
• Cardiovascular disorders including:
• Congestive heart failure (CHF): New York Heart Association (NYHA) class III (moderate) or class IV (severe) at the time of screening
• Concurrent uncontrolled hypertension defined as sustained blood pressure (BP) > 140 mmHg systolic, or > 90 mmHg diastolic despite optimal antihypertensive treatment within 7 days of the first dose of study treatment
• Any history of congenital long QT syndrome

Where it is running

• City of Hope Comprehensive Cancer Center — Duarte, California, United States
• Los Angeles General Medical Center — Los Angeles, California, United States
• USC / Norris Comprehensive Cancer Center — Los Angeles, California, United States
• City of Hope South Pasadena — South Pasadena, California, United States
• University of Chicago Comprehensive Cancer Center — Chicago, Illinois, United States
• Decatur Memorial Hospital — Decatur, Illinois, United States
• NorthShore University HealthSystem-Evanston Hospital — Evanston, Illinois, United States
• Southern Illinois University School of Medicine — Springfield, Illinois, United States
• Indiana University/Melvin and Bren Simon Cancer Center — Indianapolis, Indiana, United States
• University of Michigan Comprehensive Cancer Center — Ann Arbor, Michigan, United States
• Fox Chase Cancer Center — Philadelphia, Pennsylvania, United States
• UPMC-Magee Womens Hospital — Pittsburgh, Pennsylvania, United States
• Arthur J E Child Comprehensive Cancer Centre — Calgary, Alberta, Canada
• Cross Cancer Institute — Edmonton, Alberta, Canada
• Juravinski Cancer Centre at Hamilton Health Sciences — Hamilton, Ontario, Canada
• Kingston Health Sciences Centre — Kingston, Ontario, Canada
• London Regional Cancer Program — London, Ontario, Canada
• Ottawa Hospital and Cancer Center-General Campus — Ottawa, Ontario, Canada
• University Health Network-Princess Margaret Hospital — Toronto, Ontario, Canada

Full record on ClinicalTrials.gov

Trial information comes from ClinicalTrials.gov and is refreshed daily. TrialsForMe does not provide medical care and does not run the studies it lists.