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

NCT01935934 | Completed Phase 2 Results

• 7 other identifiers: NCI-2013-00890PHL-0869322N01CM00032N01CM00038N01CM00071UM1CA186644
• Study Type: interventional
• Target: 102
• Locations: 2 countries
• Sites: 19

Brief Summary

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.

Conditions

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

Outcome Measures

Primary Outcomes (2)

• Response Rate

  Per Response Evaluation Criteria in Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by CT: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

  At 12 weeks, then every 8 weeks during treatment; up to 12 weeks post-treatment if discontinued due to toxicities, a maximum of 16 weeks

• Progression-free Survival

  Defined as the percentage of patients progression free 12 weeks from starting treatment.

  Time from start of treatment to time of progression or death, assessed at 12 weeks

Secondary Outcomes (2)

• Number of Participants With Archival Specimens That Had C-met Amplification or Mutation

  Baseline

• Overall Survival

  Time from start of treatment to time of death, every 6 months

Study Arms (1)

Treatment (cabozantinib s-malate)

EXPERIMENTAL

Patients receive 60 mg cabozantinib s-malate PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Drug: Cabozantinib S-malate; Other: Laboratory Biomarker Analysis; Other: Pharmacological Study

Interventions

Cabozantinib S-malate DRUG

Given PO

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

Treatment (cabozantinib s-malate)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (cabozantinib s-malate)

Pharmacological Study OTHER

Correlative studies

Treatment (cabozantinib s-malate)

Eligibility Criteria

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

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
• 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

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:

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (19)

City of Hope Comprehensive Cancer Center

Duarte, California, 91010, 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

City of Hope South Pasadena

South Pasadena, California, 91030, United States

Location

University of Chicago Comprehensive Cancer Center

Chicago, Illinois, 60637, United States

Location

Decatur Memorial Hospital

Decatur, Illinois, 62526, United States

Location

NorthShore University HealthSystem-Evanston Hospital

Evanston, Illinois, 60201, United States

Location

Southern Illinois University School of Medicine

Springfield, Illinois, 62702, United States

Location

Indiana University/Melvin and Bren Simon Cancer Center

Indianapolis, Indiana, 46202, United States

Location

University of Michigan Comprehensive Cancer Center

Ann Arbor, Michigan, 48109, United States

Location

Fox Chase Cancer Center

Philadelphia, Pennsylvania, 19111, United States

Location

UPMC-Magee Womens Hospital

Pittsburgh, Pennsylvania, 15213, United States

Location

Arthur J E Child Comprehensive Cancer Centre

Calgary, Alberta, T2N 5G2, Canada

Location

Cross Cancer Institute

Edmonton, Alberta, T6G 1Z2, Canada

Location

Juravinski Cancer Centre at Hamilton Health Sciences

Hamilton, Ontario, L8V 5C2, Canada

Location

Kingston Health Sciences Centre

Kingston, Ontario, K7L 2V7, Canada

Location

London Regional Cancer Program

London, Ontario, N6A 4L6, Canada

Location

Ottawa Hospital and Cancer Center-General Campus

Ottawa, Ontario, K1H 8L6, Canada

Location

University Health Network-Princess Margaret Hospital

Toronto, Ontario, M5G 2M9, Canada

Location

Related Publications (1)

• Dhani NC, Hirte HW, Wang L, Burnier JV, Jain A, Butler MO, Welch S, Fleming GF, Hurteau J, Matsuo K, Matei D, Jimenez W, Johnston C, Cristea M, Tonkin K, Ghatage P, Lheureux S, Mehta A, Quintos J, Tan Q, Kamel-Reid S, Ludkovski O, Tsao MS, Wright JJ, Oza AM. Phase II Trial of Cabozantinib in Recurrent/Metastatic Endometrial Cancer: A Study of the Princess Margaret, Chicago, and California Consortia (NCI9322/PHL86). Clin Cancer Res. 2020 Jun 1;26(11):2477-2486. doi: 10.1158/1078-0432.CCR-19-2576. Epub 2020 Jan 28.

  PMID: 31992589 DERIVED

MeSH Terms

Conditions

Carcinoma, Endometrioid

Interventions

cabozantinib

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Endometrial Neoplasms; Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Ovarian Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Gonadal Disorders; Endocrine System Diseases

Results Point of Contact

• Title: Dr. Neesha Dhani
• Organization: University Health Network - Princess Margaret Cancer Centre

neesha.dhani@uhn.ca

416-946-4501

Study Officials

• Neesha Dhani

  University Health Network-Princess Margaret Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

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

Study Record Dates

• First Submitted: September 3, 2013
• First Posted: September 5, 2013
• Study Start: May 8, 2013
• Primary Completion: September 12, 2019
• Study Completion: October 24, 2024
• Last Updated: October 1, 2025
• Results First Posted: July 14, 2020

Record last verified: 2025-09

Locations

US (12); CA (7)