Sunitinib Malate in Treating Patients With Recurrent or Metastatic Endometrial Cancer

A Phase 2 Study of Sunitinib Malate in Recurrent or Metastatic Endometrial Carcinoma

This phase II trial studies how well sunitinib malate works in treating patients with endometrial cancer that has come back after a period of improvement (recurrent) or has spread to other places in the body (metastatic). Sunitinib 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.

Study Overview

• Status: Completed
• Conditions: Uterine Carcinosarcoma; Recurrent Uterine Corpus Carcinoma; Endometrial Endometrioid Adenocarcinoma; Endometrial Serous Adenocarcinoma; Endometrial Adenocarcinoma; Stage IVA Uterine Corpus Cancer AJCC v7; Stage IVB Uterine Corpus Cancer AJCC v7; Uterine Corpus Carcinosarcoma
• Intervention / Treatment: Drug: Sunitinib Malate

Detailed Description

PRIMARY OBJECTIVES:

I. To assess the objective response rate of recurrent or metastatic endometrial cancer to sunitinib (sunitinib malate).

II. To assess the frequency of prolonged stable disease (as defined by percentage [%] of patients alive and free from progressive disease at 6 months) in patients with recurrent or metastatic endometrial cancer treated with sunitinib.

SECONDARY OBJECTIVES:

I. To assess time-to- progression, median overall survival, and rate of one-year survival in patients with recurrent or metastatic endometrial cancer treated with sunitinib.

II. To assess the toxicity associated with sunitinib in patients with recurrent or metastatic endometrial cancer.

OUTLINE:

Patients receive sunitinib malate orally (PO) once daily (QD) on days 1-28. Courses repeat every 6 weeks in the absence of disease progression or unacceptable toxicity.

After the completion of study treatment, patients are followed up at 4 weeks and then every 3 months until relapse.

• Study Type: Interventional
• Enrollment (Actual): 34
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 1Z2
      • Cross Cancer Institute
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z 4E6
      • BCCA-Vancouver Cancer Centre
  • Ontario
    • Hamilton, Ontario, Canada, L8V 5C2
      • Juravinski Cancer Centre at Hamilton Health Sciences
    • Kingston, Ontario, Canada, K7L 2V7
      • Kingston Health Sciences Centre
    • Ottawa, Ontario, Canada, K1H 8L6
      • Ottawa Hospital and Cancer Center-General Campus
    • Toronto, Ontario, Canada, M5G 2M9
      • University Health Network-Princess Margaret Hospital
    • Toronto, Ontario, Canada, M4N 3M5
      • Odette Cancer Centre- Sunnybrook Health Sciences Centre
  • Quebec
    • Montreal, Quebec, Canada, H3T 1E2
      • Jewish General Hospital
• United States
  • California
    • Beverly Hills, California, United States, 90211
      • Tower Cancer Research Foundation
    • Duarte, California, United States, 91010
      • City of Hope Comprehensive Cancer Center
    • Los Angeles, California, United States, 90033
      • USC / Norris Comprehensive Cancer Center
    • Sacramento, California, United States, 95817
      • University of California Davis Comprehensive Cancer Center
    • South Pasadena, California, United States, 91030
      • City of Hope South Pasadena
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago Comprehensive Cancer Center
    • Decatur, Illinois, United States, 62526
      • Decatur Memorial Hospital
    • Evanston, Illinois, United States, 60201
      • Evanston Hospital CCOP
    • Harvey, Illinois, United States, 60426
      • Ingalls Memorial Hospital
    • Joliet, Illinois, United States, 60435
      • Joliet Oncology-Hematology Associates Limited
    • Maywood, Illinois, United States, 60153
      • Loyola University Medical Center
    • Peoria, Illinois, United States, 61615
      • Illinois CancerCare-Peoria
    • Springfield, Illinois, United States, 62702
      • Southern Illinois University School of Medicine
    • Springfield, Illinois, United States, 62702
      • Central Illinois Hematology Oncology Center
  • Indiana
    • Fort Wayne, Indiana, United States, 46804
      • Fort Wayne Medical Oncology and Hematology Inc - Jefferson Boulevard
    • South Bend, Indiana, United States, 46628
      • Northern Indiana Cancer Research Consortium
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • University of Maryland/Greenebaum Cancer Center
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan Comprehensive Cancer Center
    • Saint Joseph, Michigan, United States, 49085
      • Oncology Care Associates PLLC
  • Missouri
    • Saint Louis, Missouri, United States, 63141
      • Mercy Hospital Saint Louis
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Froedtert and The Medical College of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Patients must have histologically or cytologically confirmed endometrial cancer; adenocarcinoma (endometrioid and serous/papillary serous) and carcinosarcoma (ie. malignant mixed Mullerian tumor [MMMT]) of the uterus will be investigated; patients with other histologies (eg. squamous cell carcinoma or leiomyosarcoma) are excluded
• 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) as >= 20 mm with conventional techniques or as >= 10 mm with spiral computed tomography (CT) scan; indicator lesions must not have been previously treated with surgery, radiotherapy, or radiofrequency ablation
• Previously treated patients must have evidence of progressive disease, either clinically or radiographically, as assessed by the investigator
• Eligible patients may have received no more than one prior cytotoxic chemotherapy regimen for recurrent, locally-advanced, or metastatic disease; if the prior chemotherapy was an anthracycline, they may have received no more than 6 cycles (or less than 450 mg/m^2 doxorubicin); patients must have completed any previous chemotherapy a minimum of 4 weeks (or 6 weeks if the regimen contained carmustine [BCNU] or mitomycin) prior to study registration; prior investigational treatment is permissible (as long as such treatment completed 4 weeks prior to registration)
• Life expectancy of greater than 3 months
• Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60)
• Leukocytes >= 3,000/mcL
• Absolute neutrophil count (ANC) >= 1,500/mcL
• Platelets >= 100,000/mcL
• Hemoglobin >= 100 g/dL
• Serum calcium =< 12.0 mg/dL (=< 3.0 mmol/L)
• Total serum bilirubin within normal institutional limits
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 X institutional upper limit of normal
• Creatinine within normal institutional limits OR creatinine clearance >= 60 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal
• Serum lipase =< 1.5 x institutional upper limit of normal
• Serum amylase =< 1.5 x institutional upper limit of normal
• Thyroid stimulating hormone (TSH)/T3/T4 within normal institutional limits
• Magnesium >= 0.5 mmol/L
• Patients must have corrected QT interval (QTc) < 500 msec

• The following group of patients are eligible provided they have normal baseline cardiac function (as determined by estimate of left ventricular ejection fraction [LVEF] on echocardiogram or multi-gated acquisition scan [MUGA]):

  • Those with a history of congestive heart failure, provided they are no greater than New York Heart Association (NYHA) class I and on treatment at baseline
  • Those with prior anthracycline exposure
  • Those who have received prior central thoracic radiation that included the heart in the radiotherapy port
• Women of childbearing potential 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; all women of childbearing potential must have a negative pregnancy test prior to receiving sunitinib; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
• 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; at least 4 weeks must have elapsed since any major surgery
• Patients may not be receiving any other investigational agents
• Patients who have received prior treatment with any other antiangiogenic agent (e.g., bevacizumab, sorafenib, pazopanib, AZD2171, PTK787, vascular endothelial growth factor [VEGF] Trap, etc.) are ineligible
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to sunitinib
• Patients who have a history of serious ventricular arrhythmias (ventricular tachycardia [VT] or ventricular fibrillation [VF] equal to or greater than 3 beats in a row), QTc prolongation (defined as a QTc interval equal to or greater than 500 msec) or other significant electrocardiogram (ECG) abnormalities are excluded
• Patients with poorly controlled hypertension (systolic blood pressure of 140 mmHg or higher or diastolic blood pressure of 90 mmHg or higher) are ineligible
• Patients who require use of therapeutic doses of coumarin-derivative anticoagulants such as warfarin are excluded, although doses of up to 2 mg daily are permitted for prophylaxis of thrombosis; Note: Low molecular weight heparin is permitted provided the patient's prothrombin time (PT) international normalized ratio (INR) is =< 1.5
• Patients with any condition (e.g., gastrointestinal tract disease resulting in an inability to take oral medication or a requirement for intravenous [IV] alimentation, prior surgical procedures affecting absorption, or active peptic ulcer disease) that impairs their ability to swallow and retain sunitinib tablets are excluded

• Patients with any of the following conditions are excluded:

  • Serious or non-healing wound, ulcer, or bone fracture
  • History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 28 days of treatment
  • Any history of cerebrovascular accident (CVA) or transient ischemic attack within 12 months prior to study entry
  • History of myocardial infarction, cardiac arrhythmia, stable/unstable angina, symptomatic congestive heart failure, or coronary/peripheral artery bypass graft or stenting within 12 months prior to study entry
  • History of pulmonary embolism within the past 12 months
  • Class III or IV heart failure as defined by the NYHA functional classification system
  • Pre-existing adrenal insufficiency (primary or secondary)
• The eligibility of patients taking medications that are potent inducers or inhibitors of cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) will be determined following a review of their case by the Principal Investigator; every effort should be made to switch patients taking such agents or substances to other medications, particularly patients who are taking enzyme-inducing anticonvulsant agents
• Patients with a pre-existing thyroid abnormality who are unable to maintain thyroid function in the normal range with medication are ineligible
• Patients with known brain metastases should be excluded
• Patients with uncontrolled intercurrent illness including, but not limited to, ongoing or active infections or psychiatric illness/social situations that would limit compliance with study requirements are ineligible
• Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated with sunitinib malate
• Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment (sunitinib malate); Patients receive sunitinib malate PO QD on days 1-28. Courses repeat every 6 weeks in the absence of disease progression or unacceptable toxicity.	Drug: Sunitinib Malate; Given PO; Other Names: Sutent; SU011248; SU11248; sunitinib

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate	Objective response rate, defined as the rate of complete or partial response as defined by the Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI and/or CT: Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD), neither sufficient shrinkage to qualify for a Partial Response nor sufficient increase to qualify for Progression of Disease (PD); PD, 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions; Complete Response (CR), disappearance of all target lesions.	Up to 7 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Prolonged Stable Disease	Described as the best response of stable disease that is maintained for atleast 6 months	Up to 7 years
Overall Survival	Estimated using the Kaplan-Meier method.	Up to 7 years
Number of Participants With Adverse Effects Assessed by CTCAE Version 3.0	Number of participants that experience at east 1 adverse event while on trial, according to the CTCAE.	Up to 7 years
Time to Progression	The length of time from the date of diagnosis or the start of treatment for a disease until the disease starts to get worse or spread to other parts of the body. Assessed by Kaplan and Meier method	Up to 7 years

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Amit M Oza, University Health Network-Princess Margaret Hospital

Publications and helpful links

General Publications

• Castonguay V, Lheureux S, Welch S, Mackay HJ, Hirte H, Fleming G, Morgan R, Wang L, Blattler C, Ivy PS, Oza AM. A phase II trial of sunitinib in women with metastatic or recurrent endometrial carcinoma: a study of the Princess Margaret, Chicago and California Consortia. Gynecol Oncol. 2014 Aug;134(2):274-80. doi: 10.1016/j.ygyno.2014.05.016. Epub 2014 May 29.

Study record dates

Study Major Dates

• Study Start (Actual): April 30, 2007
• Primary Completion (Actual): February 12, 2019
• Study Completion (Actual): February 12, 2019

Study Registration Dates

• First Submitted: May 23, 2007
• First Submitted That Met QC Criteria: May 23, 2007
• First Posted (Estimate): May 24, 2007

Study Record Updates

• Last Update Posted (Actual): February 17, 2020
• Last Update Submitted That Met QC Criteria: February 14, 2020
• Last Verified: February 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Uterine Neoplasms; Genital Neoplasms, Female; Endocrine System Diseases; Disease Attributes; Ovarian Diseases; Adnexal Diseases; Gonadal Disorders; Neoplasms, Complex and Mixed; Sarcoma; Cystadenocarcinoma; Neoplasms, Cystic, Mucinous, and Serous; Ovarian Neoplasms; Endometrial Neoplasms; Carcinoma; Recurrence; Adenocarcinoma; Carcinosarcoma; Mixed Tumor, Mullerian; Cystadenocarcinoma, Serous; Carcinoma, Endometrioid; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Protein Kinase Inhibitors; Sunitinib
• Other Study ID Numbers: NCI-2009-00210 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); N01CM62201 (U.S. NIH Grant/Contract); N01CM62203 (U.S. NIH Grant/Contract); N01CM62209 (U.S. NIH Grant/Contract); PHL-062; CDR0000513153; 7713 (CTEP)