Sunitinib Malate in Treating Patients With Recurrent or Metastatic Endometrial Cancer

NCT ID: NCT00478426

Last Updated: 2020-02-17

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 34 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-04-30
• Study Completion Date: 2019-02-12

Brief Summary

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.

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.

Conditions

Endometrial Adenocarcinoma; Endometrial Endometrioid Adenocarcinoma; Endometrial Serous Adenocarcinoma; Recurrent Uterine Corpus Carcinoma; Stage IVA Uterine Corpus Cancer AJCC v7; Stage IVB Uterine Corpus Cancer AJCC v7; Uterine Carcinosarcoma; Uterine Corpus Carcinosarcoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Sunitinib Malate

Intervention Type: DRUG

Given PO

Interventions

Sunitinib Malate

Given PO

Intervention Type: DRUG

Other Intervention Names

SU011248; SU11248; sunitinib; Sutent

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Amit M Oza

Role: PRINCIPAL_INVESTIGATOR

University Health Network-Princess Margaret Hospital

Locations

Tower Cancer Research Foundation

Beverly Hills, California, United States

City of Hope Comprehensive Cancer Center

Duarte, California, United States

USC / Norris Comprehensive Cancer Center

Los Angeles, California, United States

University of California Davis Comprehensive Cancer Center

Sacramento, 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

Evanston Hospital CCOP

Evanston, Illinois, United States

Ingalls Memorial Hospital

Harvey, Illinois, United States

Joliet Oncology-Hematology Associates Limited

Joliet, Illinois, United States

Loyola University Medical Center

Maywood, Illinois, United States

Illinois CancerCare-Peoria

Peoria, Illinois, United States

Central Illinois Hematology Oncology Center

Springfield, Illinois, United States

Southern Illinois University School of Medicine

Springfield, Illinois, United States

Fort Wayne Medical Oncology and Hematology Inc - Jefferson Boulevard

Fort Wayne, Indiana, United States

Northern Indiana Cancer Research Consortium

South Bend, Indiana, United States

University of Maryland/Greenebaum Cancer Center

Baltimore, Maryland, United States

University of Michigan Comprehensive Cancer Center

Ann Arbor, Michigan, United States

Oncology Care Associates PLLC

Saint Joseph, Michigan, United States

Mercy Hospital Saint Louis

St Louis, Missouri, United States

Froedtert and the Medical College of Wisconsin

Milwaukee, Wisconsin, United States

Cross Cancer Institute

Edmonton, Alberta, Canada

BCCA-Vancouver Cancer Centre

Vancouver, British Columbia, Canada

Juravinski Cancer Centre at Hamilton Health Sciences

Hamilton, Ontario, Canada

Kingston Health Sciences Centre

Kingston, Ontario, Canada

Ottawa Hospital and Cancer Center-General Campus

Ottawa, Ontario, Canada

Odette Cancer Centre- Sunnybrook Health Sciences Centre

Toronto, Ontario, Canada

University Health Network-Princess Margaret Hospital

Toronto, Ontario, Canada

Jewish General Hospital

Montreal, Quebec, Canada

Countries

United States; Canada

References

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.

Reference Type: RESULT

PMID: 24882554 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

NCI-2009-00210

Identifier Type: REGISTRY

Identifier Source: secondary_id

PHL-062

Identifier Type: -

Identifier Source: secondary_id

CDR0000513153

Identifier Type: -

Identifier Source: secondary_id

7713

Identifier Type: OTHER

Identifier Source: secondary_id

7713

Identifier Type: OTHER

Identifier Source: secondary_id

N01CM62201

Identifier Type: NIH

Identifier Source: secondary_id

View Link

N01CM62203

Identifier Type: NIH

Identifier Source: secondary_id

View Link

N01CM62209

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NCI-2009-00210

Identifier Type: -

Identifier Source: org_study_id