Sunitinib Malate in Treating Patients With Recurrent or Metastatic Endometrial Cancer

Endometrial Adenocarcinoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00478426
• Other study ID #: NCI-2009-00210
• Secondary ID: NCI-2009-00210PH
• Status: Completed
• Phase: Phase 2
• Start date: April 30, 2007
• Est. completion date: February 12, 2019

Study information

• Verified date: February 2020
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 34
• Est. completion date: February 12, 2019
• Est. primary completion date: February 12, 2019
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Adenocarcinoma
• Carcinoma
• Carcinoma, Endometrioid
• Carcinosarcoma
• Endometrial Adenocarcinoma
• Endometrial Endometrioid Adenocarcinoma
• Endometrial Serous Adenocarcinoma
• Mixed Tumor, Mullerian
• Recurrent Uterine Corpus Carcinoma
• Stage IVA Uterine Corpus Cancer AJCC v7
• Stage IVB Uterine Corpus Cancer AJCC v7
• Uterine Carcinosarcoma
• Uterine Corpus Carcinosarcoma

Intervention

Drug:
• Sunitinib Malate
Given PO

Locations

Country	Name	City	State
Canada	Cross Cancer Institute	Edmonton	Alberta
Canada	Juravinski Cancer Centre at Hamilton Health Sciences	Hamilton	Ontario
Canada	Kingston Health Sciences Centre	Kingston	Ontario
Canada	Jewish General Hospital	Montreal	Quebec
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	BCCA-Vancouver Cancer Centre	Vancouver	British Columbia
United States	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan
United States	University of Maryland/Greenebaum Cancer Center	Baltimore	Maryland
United States	Tower Cancer Research Foundation	Beverly Hills	California
United States	University of Chicago Comprehensive Cancer Center	Chicago	Illinois
United States	Decatur Memorial Hospital	Decatur	Illinois
United States	City of Hope Comprehensive Cancer Center	Duarte	California
United States	Evanston Hospital CCOP	Evanston	Illinois
United States	Fort Wayne Medical Oncology and Hematology Inc - Jefferson Boulevard	Fort Wayne	Indiana
United States	Ingalls Memorial Hospital	Harvey	Illinois
United States	Joliet Oncology-Hematology Associates Limited	Joliet	Illinois
United States	USC / Norris Comprehensive Cancer Center	Los Angeles	California
United States	Loyola University Medical Center	Maywood	Illinois
United States	Froedtert and the Medical College of Wisconsin	Milwaukee	Wisconsin
United States	Illinois CancerCare-Peoria	Peoria	Illinois
United States	University of California Davis Comprehensive Cancer Center	Sacramento	California
United States	Oncology Care Associates PLLC	Saint Joseph	Michigan
United States	Mercy Hospital Saint Louis	Saint Louis	Missouri
United States	Northern Indiana Cancer Research Consortium	South Bend	Indiana
United States	City of Hope South Pasadena	South Pasadena	California
United States	Central Illinois Hematology Oncology Center	Springfield	Illinois
United States	Southern Illinois University School of Medicine	Springfield	Illinois

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Countries where clinical trial is conducted

United States,  Canada, 

References & Publications (1)

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 Califo — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	Overall Survival	Estimated using the Kaplan-Meier method.	Up to 7 years
Secondary	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
Secondary	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