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

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2014 by National Cancer Institute (NCI)
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT01935934
First received: September 3, 2013
Last updated: September 16, 2014
Last verified: September 2014
  Purpose

This phase II trial studies how well cabozantinib-s-malate works in treating patients with recurrent or metastatic endometrial cancer. 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.


Condition Intervention Phase
Endometrial Adenosquamous Cell Carcinoma
Endometrial Clear Cell Carcinoma
Endometrial Papillary Serous Carcinoma
Recurrent Endometrial Carcinoma
Stage IVA Endometrial Carcinoma
Stage IVB Endometrial Carcinoma
Drug: cabozantinib-s-malate
Other: laboratory biomarker analysis
Other: pharmacological study
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 2 Study of XL184 (Cabozantinib) in Recurrent or Metastatic Endometrial Cancer

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Response rate using RECIST version 1.1 [ Time Frame: Up to 12 weeks post-treatment ] [ Designated as safety issue: No ]
  • Progression-free survival [ Time Frame: Time from start of treatment to time of progression or death, assessed at 12 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Baseline molecular status of archival tumor (c-met amplification & mutation status) [ Time Frame: Baseline ] [ Designated as safety issue: No ]
  • Pharmacodynamic responses in levels of soluble, circulating angiogenic factors [ Time Frame: Baseline and day 1 of course 2 ] [ Designated as safety issue: No ]

Estimated Enrollment: 36
Study Start Date: April 2013
Estimated Primary Completion Date: November 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (cabozantinib-s-malate)
Patients receive 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
Given PO
Other Names:
  • BMS-907351
  • Cometriq
  • XL184
Other: laboratory biomarker analysis
Correlative studies
Other: pharmacological study
Correlative studies
Other Name: pharmacological studies

Detailed Description:

PRIMARY OBJECTIVES:

I. Determine efficacy of single agent cabozantinib in women previously receiving one line of chemotherapy for metastatic endometrial cancer or with progression within 12 months of completing adjuvant therapy, with co-primary endpoints of objective response rate by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and progression-free-survival at 12 weeks (PFS).

SECONDARY OBJECTIVES:

I. Correlation of clinical response with: baseline molecular status of archival tumor (hepatocyte growth factor receptor [c-met] amplification & mutation status).

OUTLINE:

Patients receive cabozantinib-s-malate orally (PO) once daily (QD) on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 4 weeks.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients must have histologically or cytologically confirmed metastatic endometrial cancer; eligible histologies for the experimental cohort are: endometrioid, serous or mixed; eligible histologies for the exploratory cohort are: carcinosarcoma, clear cell or adenosquamous
  • 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; 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; 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

Exclusion Criteria:

  • Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier
  • The subject has received cytotoxic chemotherapy (including investigational cytotoxic chemotherapy) or biologic agents (e.g., cytokines or antibodies) within 3 weeks, or nitrosoureas/mitomycin C within 6 weeks before the first dose of study treatment
  • 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 within 7 days before the first dose of study treatment
  • The subject requires 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
  • The subject requires chronic concomitant treatment of strong cytochrome P450 family 3, subfamily A, polypeptide 4 (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 radiographic evidence of cavitating pulmonary lesion(s)
  • 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
      • Any of the following within 6 months before the first dose of study treatment:

        • Unstable angina pectoris
        • Clinically-significant cardiac arrhythmias
        • Stroke (including transient ischemic attack [TIA], or other ischemic event)
        • Myocardial infarction
        • Thromboembolic event requiring therapeutic anticoagulation (note: subjects with a venous filter [e.g. vena cava filter] are not eligible for this study)
  • Gastrointestinal disorders particularly those associated with a high risk of perforation or fistula formation including:

    • Any of the following within 28 days before the first dose of study treatment

      • Intra-abdominal tumor/metastases invading GI mucosa
      • Active peptic ulcer disease,
      • Inflammatory bowel disease (including ulcerative colitis and Crohn's disease), diverticulitis, cholecystitis, symptomatic cholangitis or appendicitis
      • Malabsorption syndrome
    • Any of the following within 6 months before the first dose of study treatment:

      • Abdominal fistula
      • Gastrointestinal perforation
      • Bowel obstruction or gastric outlet obstruction
      • Intra-abdominal abscess; note: complete resolution of an intra-abdominal abscess must be confirmed prior to initiating treatment with cabozantinib even if the abscess occurred more than 6 months before the first dose of study treatment
  • Other disorders associated with a high risk of fistula formation including percutaneous endoscopic gastrostomy (PEG) tube placement within 3 months before the first dose of study therapy
  • Other clinically significant disorders such as:

    • Active infection requiring systemic treatment within 28 days before the first dose of study treatment
    • Serious non-healing wound/ulcer/bone fracture within 28 days before the first dose of study treatment
    • History of organ transplant
    • Concurrent uncompensated hypothyroidism or thyroid dysfunction within 7 days before the first dose of study treatment
    • History of major surgery as follows:

      • Major surgery within 3 months of the first dose of cabozantinib if there were no wound healing complications or within 6 months of the first dose of cabozantinib if there were wound complications
      • Minor surgery within 1 month of the first dose of cabozantinib if there were no wound healing complications or within 3 months of the first dose of cabozantinib if there were wound complications

        • In addition, complete wound healing from prior surgery must be confirmed at least 28 days before the first dose of cabozantinib irrespective of the time from surgery
  • The subject is unable to swallow tablets
  • The subject has a corrected QT interval calculated by the Fridericia formula (QTcF) > 500 ms within 28 days before randomization; note: if initial QTcF is found to be > 500 ms, two additional electrocardiograms (EKGs) separated by at least 3 minutes should be performed; if the average of these three consecutive results for QTcF is =< 500 ms, the subject meets eligibility in this regard
  • The subject is unable or unwilling to abide by the study protocol or cooperate fully with the investigator or designee
  • The subject has had evidence within 2 years of the start of study treatment of another malignancy which required systemic treatment
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to XL184
  • Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated with XL184
  • Known human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01935934

Locations
United States, California
City of Hope Recruiting
Duarte, California, United States, 91010
Contact: Mihaela C. Cristea    626-256-4673    mcristea@coh.org   
Principal Investigator: Mihaela C. Cristea         
USC Norris Comprehensive Cancer Center Recruiting
Los Angeles, California, United States, 90033
Contact: Agustin A. Garcia    323-865-3900    Agustin.Garcia@med.usc.edu   
Principal Investigator: Agustin A. Garcia         
University of California at Davis Cancer Center Recruiting
Sacramento, California, United States, 95817
Contact: Sidney A. Scudder    916-734-3772    sidney.scudder@ucdmc.ucdavis.edu   
Principal Investigator: Sidney A. Scudder         
City of Hope South Pasadena Recruiting
South Pasadena, California, United States, 91030
Contact: Stephen C. Koehler    626-396-2900    Skoehler@cohmg.com   
Principal Investigator: Stephen C. Koehler         
United States, Illinois
University of Chicago Recruiting
Chicago, Illinois, United States, 60637
Contact: Gini F. Fleming    773-702-6712    gfleming@medicine.bsd.uchicago.edu   
Principal Investigator: Gini F. Fleming         
Decatur Memorial Hospital Recruiting
Decatur, Illinois, United States, 62526
Contact: James L. Wade    217-876-6600    JLWADE3@sbcglobal.net   
Principal Investigator: James L. Wade         
NorthShore University HealthSystem-Evanston Hospital Recruiting
Evanston, Illinois, United States, 60201
Contact: Jean A. Hurteau    847-570-2639    jhurteau@uchicago.edu   
Principal Investigator: Jean A. Hurteau         
United States, Indiana
Indiana University Medical Center Recruiting
Indianapolis, Indiana, United States, 46202
Contact: Daniela E. Matei    317-278-0070    dmatei@iu.edu   
Principal Investigator: Daniela E. Matei         
United States, Michigan
University of Michigan Recruiting
Ann Arbor, Michigan, United States, 48109
Contact: Ronald J. Buckanovich    734-764-2395    ronaldbu@umich.edu   
Principal Investigator: Ronald J. Buckanovich         
Wayne State University/Karmanos Cancer Institute Recruiting
Detroit, Michigan, United States, 48201
Contact: Robert T. Morris    313-576-9435    rmorris@med.wayne.edu   
Principal Investigator: Robert T. Morris         
United States, Pennsylvania
Fox Chase Cancer Center Recruiting
Philadelphia, Pennsylvania, United States, 19111
Contact: Angela Jain    215-728-2871    Angela.Jain@fccc.edu   
Principal Investigator: Angela Jain         
Magee-Womens Hospital of UPMC Recruiting
Pittsburgh, Pennsylvania, United States, 15213
Contact: Robert P. Edwards    412-641-5418    edwarp@mail.magee.edu   
Principal Investigator: Robert P. Edwards         
Canada, Alberta
Tom Baker Cancer Centre Recruiting
Calgary, Alberta, Canada, T2N 4N2
Contact: Prafull Ghatage    403-521-3721    Prafull.Ghatage@albertahealthservices.ca   
Principal Investigator: Prafull Ghatage         
Cross Cancer Institute Recruiting
Edmonton, Alberta, Canada, T6G 1Z2
Contact: Katia S. Tonkin    780-432-8514    Katia.Tonkin@albertahealthservices.ca   
Principal Investigator: Katia S. Tonkin         
Canada, British Columbia
BCCA-Vancouver Cancer Centre Recruiting
Vancouver, British Columbia, Canada, V5Z 4E6
Contact: Amit M. Oza    416-946-2818    amit.oza@uhn.ca   
Principal Investigator: Amit M. Oza         
Canada, Ontario
Juravinski Cancer Centre at Hamilton Health Sciences Recruiting
Hamilton, Ontario, Canada, L8V 5C2
Contact: Holger W. Hirte    905-387-9495    Hal.hirte@jcc.hhsc.ca   
Principal Investigator: Holger W. Hirte         
Cancer Centre of Southeastern Ontario at Kingston General Hospital Recruiting
Kingston, Ontario, Canada, K7L 5P9
Contact: James J. Biagi    613-544-2630    jim.biagi@krcc.on.ca   
Principal Investigator: James J. Biagi         
London Regional Cancer Program Recruiting
London, Ontario, Canada, N6A 4L6
Contact: Stephen A. Welch    519-685-8640    Stephen.welch@lhsc.on.ca   
Principal Investigator: Stephen A. Welch         
Ottawa General Hospital Recruiting
Ottawa, Ontario, Canada, K1H 8L6
Contact: Johanne I. Weberpals    613-737-8899    jwebserpals@ottawahospital.on.ca   
Principal Investigator: Johanne I. Weberpals         
University Health Network-Princess Margaret Hospital Recruiting
Toronto, Ontario, Canada, M5G 2M9
Contact: Amit M. Oza    416-946-2818    amit.oza@uhn.ca   
Principal Investigator: Amit M. Oza         
Sponsors and Collaborators
Investigators
Principal Investigator: Amit Oza University Health Network-Princess Margaret Hospital
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT01935934     History of Changes
Obsolete Identifiers: NCT01815151
Other Study ID Numbers: NCI-2013-00890, NCI-2013-00890, PHL-086, 9322, N01CM00032
Study First Received: September 3, 2013
Last Updated: September 16, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Endometrial Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Uterine Neoplasms
Genital Neoplasms, Female
Urogenital Neoplasms
Neoplasms by Site
Neoplasms, Complex and Mixed
Neoplasms, Cystic, Mucinous, and Serous
Carcinoma
Carcinoma, Adenosquamous
Cystadenocarcinoma, Serous
Adenocarcinoma, Clear Cell
Adenomyoepithelioma
Uterine Diseases
Genital Diseases, Female
Cystadenocarcinoma
Adenocarcinoma

ClinicalTrials.gov processed this record on September 18, 2014