Clinical trial NCT00478426: Sunitinib Malate in Treating Patients With Recurrent or Metastatic Endometrial Cancer
Official title: A Phase 2 Study of Sunitinib Malate in Recurrent or Metastatic Endometrial Carcinoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
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
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2007-05-24
Enrollment: 34
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Objective Response Rate
timeFrame: Up to 7 years
Secondary outcomes:
measure: Number of Participants With Prolonged Stable Disease
timeFrame: Up to 7 years
measure: Overall Survival
timeFrame: Up to 7 years
measure: Number of Participants With Adverse Effects Assessed by CTCAE Version 3.0
timeFrame: Up to 7 years
measure: Time to Progression
timeFrame: Up to 7 years
Other outcomes:
Locations:
city: Beverly Hills
country: United States
facility: Tower Cancer Research Foundation
state: California
city: Duarte
country: United States
facility: City of Hope Comprehensive Cancer Center
state: California
city: Los Angeles
country: United States
facility: USC / Norris Comprehensive Cancer Center
state: California
city: Sacramento
country: United States
facility: University of California Davis Comprehensive Cancer Center
state: California
city: South Pasadena
country: United States
facility: City of Hope South Pasadena
state: California
city: Chicago
country: United States
facility: University of Chicago Comprehensive Cancer Center
state: Illinois
city: Decatur
country: United States
facility: Decatur Memorial Hospital
state: Illinois
city: Evanston
country: United States
facility: Evanston Hospital CCOP
state: Illinois
city: Harvey
country: United States
facility: Ingalls Memorial Hospital
state: Illinois
city: Joliet
country: United States
facility: Joliet Oncology-Hematology Associates Limited
state: Illinois
city: Maywood
country: United States
facility: Loyola University Medical Center
state: Illinois
city: Peoria
country: United States
facility: Illinois CancerCare-Peoria
state: Illinois
city: Springfield
country: United States
facility: Central Illinois Hematology Oncology Center
state: Illinois
city: Springfield
country: United States
facility: Southern Illinois University School of Medicine
state: Illinois
city: Fort Wayne
country: United States
facility: Fort Wayne Medical Oncology and Hematology Inc - Jefferson Boulevard
state: Indiana
city: South Bend
country: United States
facility: Northern Indiana Cancer Research Consortium
state: Indiana
city: Baltimore
country: United States
facility: University of Maryland/Greenebaum Cancer Center
state: Maryland
city: Ann Arbor
country: United States
facility: University of Michigan Comprehensive Cancer Center
state: Michigan
city: Saint Joseph
country: United States
facility: Oncology Care Associates PLLC
state: Michigan
city: Saint Louis
country: United States
facility: Mercy Hospital Saint Louis
state: Missouri
city: Milwaukee
country: United States
facility: Froedtert and the Medical College of Wisconsin
state: Wisconsin
city: Edmonton
country: Canada
facility: Cross Cancer Institute
state: Alberta
city: Vancouver
country: Canada
facility: BCCA-Vancouver Cancer Centre
state: British Columbia
city: Hamilton
country: Canada
facility: Juravinski Cancer Centre at Hamilton Health Sciences
state: Ontario
city: Kingston
country: Canada
facility: Kingston Health Sciences Centre
state: Ontario
city: Ottawa
country: Canada
facility: Ottawa Hospital and Cancer Center-General Campus
state: Ontario
city: Toronto
country: Canada
facility: Odette Cancer Centre- Sunnybrook Health Sciences Centre
state: Ontario
city: Toronto
country: Canada
facility: University Health Network-Princess Margaret Hospital
state: Ontario
city: Montreal
country: Canada
facility: Jewish General Hospital
state: Quebec
Study officials:
affiliation: University Health Network-Princess Margaret Hospital
name: Amit M Oza
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.