Sunitinib in Treating Patients With Recurrent or Metastatic Endometrial Cancer

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00478426
First received: May 23, 2007
Last updated: January 15, 2014
Last verified: January 2014
  Purpose

This phase II trial is studying how well sunitinib works in treating patients with recurrent or metastatic endometrial cancer. 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.


Condition Intervention Phase
Endometrial Adenocarcinoma
Endometrial Papillary Serous Carcinoma
Recurrent Endometrial Carcinoma
Recurrent Uterine Sarcoma
Stage IV Endometrial Carcinoma
Stage IV Uterine Sarcoma
Uterine Carcinosarcoma
Drug: sunitinib malate
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 Sunitinib Malate in Recurrent or Metastatic Endometrial Carcinoma

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Objective response rate (complete or partial response) assessed by Response Evaluation Criteria for Solid Tumors (RECIST) [ Time Frame: Up to 4 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Percentage of patients alive and free from progressive disease assessed by RECIST [ Time Frame: At 6 months ] [ Designated as safety issue: No ]
  • Overall survival [ Time Frame: Up to 4 years ] [ Designated as safety issue: No ]
  • Frequency and severity of observed adverse effects assessed by Common Terminology Criteria for Adverse Events version 3.0 (CTCAE v3.0) [ Time Frame: Up to 4 weeks ] [ Designated as safety issue: Yes ]
  • Time to progression assessed by RECIST [ Time Frame: Up to 4 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 30
Study Start Date: April 2007
Estimated Primary Completion Date: June 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I
Patients receive sunitinib malate PO QD on days 1-28.
Drug: sunitinib malate
Given PO
Other Names:
  • SU11248
  • sunitinib
  • Sutent

Detailed Description:

PRIMARY OBJECTIVES:

I. Determine the objective response rate in patients with recurrent or metastatic endometrial cancer treated with sunitinib malate.

II. Determine the frequency of prolonged stable disease (as defined by percentage of patients alive and free from progressive disease at 6 months) in patients treated with this drug.

SECONDARY OBJECTIVES:

I. Determine time to progression, median overall survival, and rate of one-year survival in patients treated with this drug.

II. Determine the toxicity of this drug in these patients.

OUTLINE: This is an open-label, multicenter study.

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

After the completion of study treatment, patients are followed at 4 weeks.

  Eligibility

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

Inclusion Criteria:

  • Histologically or cytologically confirmed endometrial cancer; adenocarcinoma (endometrioid and serous, or papillary serous) and carcinosarcoma (ie. malignant mixed mullerian tumor [MMMT] of the uterus will be investigated; patients with other histologies (e.g., 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 lesion >= 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/m2 doxorubicin); patients must have completed any previous chemotherapy a minimum of 4 weeks (or 6 weeks if the regimen contained 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 > 3 months
  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-2 OR Karnofsky PS 60-100%
  • Leukocytes >= 3,000/mcL
  • Absolute neutrophil count (ANC) >= 1,500/mcL
  • Platelet count >= 100,000/mcL
  • Hemoglobin >= 100 mg/dL
  • Serum calcium =< 12.0 mg/dL (=< 3.0 mmol/L)
  • Total serum bilirubin within normal institutional limits
  • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 times upper limit of normal
  • Creatinine normal OR creatinine clearance >= 60 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal
  • Serum lipase or serum amylase =< 1.5 times institutional upper limit serum amylase normal
  • Thyroid stimulating hormone (TSH), T3, or T4 within normal institutional limits
  • Magnesium >= 0.5 mmol/L
  • Patients must have QTc < 500 msec
  • Patients meeting any of the following criteria are eligible provided they have normal left ventricular ejection fraction (LVEF) on echocardiogram (ECHO) or multi-gated acquisition (MUGA) scan:

    • History of congestive heart failure with New York Heart Association (NYHA) =< class I and on treatment
    • Prior anthracycline exposure
    • Received prior central thoracic radiation that included the heart in the radiotherapy port
  • The effects of sunitinib on the developing human fetus at the recommended therapeutic dose are unknown; for this reason and because antiangiogenic agents are known to be teratogenic, 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
  • No prior antiangiogenic agents (e.g., bevacizumab, sorafenib, pazopanib, AZD2171, vatalanib, vascular endothelial growth factor [VEGF] Trap)
  • 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 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 New York Heart Association (NYHA) functional classification system
    • Pre-existing adrenal insufficiency (primary or secondary)
  • Because sunitinib is metabolized primarily by the cytochrome P450 3A4 (CYP3A4) liver enzyme, the eligibility of patients taking medications that are potent inducers or inhibitors of that enzyme 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 because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events
  • 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 because sunitinib is an antiangiogenic agent with the potential for teratogenic or abortifacient effects; because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with sunitinib, breastfeeding should be discontinued if the mother is treated with sunitinib malate
  • Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with sunitinib; in addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy; appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00478426

Locations
United States, California
Tower Cancer Research Foundation
Beverly Hills, California, United States, 90211-1850
City of Hope
Duarte, California, United States, 91010
USC Norris Comprehensive Cancer Center
Los Angeles, California, United States, 90033
City of Hope Medical Group Inc
Pasadena, California, United States, 91105
UC Davis Comprehensive Cancer Center
Sacramento, California, United States, 95817
United States, Illinois
University of Chicago Comprehensive Cancer Center
Chicago, Illinois, United States, 60637-1470
Canada, Alberta
Cross Cancer Institute
Edmonton, Alberta, Canada, T6G 1Z2
Canada, British Columbia
BCCA-Vancouver Cancer Centre
Vancouver, British Columbia, Canada, V5Z 4E6
Canada, Ontario
Juravinski Cancer Centre at Hamilton Health Sciences
Hamilton, Ontario, Canada, L8V 5C2
Cancer Centre of Southeastern Ontario at Kingston General Hospital
Kingston, Ontario, Canada, K7L 5P9
Ottawa General Hospital
Ottawa, Ontario, Canada, K1H 8L6
University Health Network-Princess Margaret Hospital
Toronto, Ontario, Canada, M5G 2M9
Odette Cancer Centre- Sunnybrook Health Sciences Centre
Toronto, Ontario, Canada, M4N 3M5
Canada, Quebec
Jewish General Hospital
Montreal, Quebec, Canada, H3T 1E2
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: NCT00478426     History of Changes
Other Study ID Numbers: NCI-2009-00210, NCI-2009-00210, PHL-062, CDR0000513153, PHL-062, 7713, N01CM62209, N01CM62201, N01CM62203
Study First Received: May 23, 2007
Last Updated: January 15, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Adenocarcinoma
Carcinoma
Carcinosarcoma
Mixed Tumor, Mullerian
Cystadenocarcinoma, Serous
Uterine Neoplasms
Endometrial Neoplasms
Sarcoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Complex and Mixed
Neoplasms, Connective and Soft Tissue
Cystadenocarcinoma
Neoplasms, Cystic, Mucinous, and Serous
Genital Neoplasms, Female
Urogenital Neoplasms
Neoplasms by Site
Uterine Diseases
Genital Diseases, Female
Sunitinib
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors

ClinicalTrials.gov processed this record on April 15, 2014