Sunitinib in Treating Patients With Recurrent or Persistent Leiomyosarcoma of the Uterus

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00378911
First received: September 19, 2006
Last updated: June 11, 2014
Last verified: December 2012
  Purpose

This phase II trial is studying how well sunitinib works in treating patients with recurrent or persistent leiomyosarcoma of the uterus. 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
Recurrent Uterine Sarcoma
Uterine Leiomyosarcoma
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 II Evaluation of Sunitinib Malate (Sutent®, SU11248, NCI-Supplied Agent , NSC # 736511) in the Treatment of Recurrent or Persistent Leiomyosarcoma of the Uterus

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Progression-free survival [ Time Frame: From study entry until disease progression, death or date of last contact., assessed up to 6 months ] [ Designated as safety issue: No ]
  • Objective tumor response according to GOG RECIST criteria [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
  • Frequency and severity of adverse events as assessed by CTCAE v 3.0 [ Time Frame: Up to 5 years ] [ Designated as safety issue: Yes ]
    The frequency and severity of all toxicities will be tabulated.


Secondary Outcome Measures:
  • Duration of progression-free survival [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    Characterized graphically and using descriptive statistics such as median survival.

  • Duration of overall survival [ Time Frame: From entry into the study to death or the date of last contact, assessed up to 5 years ] [ Designated as safety issue: No ]
    Characterized graphically and using descriptive statistics such as median survival.


Enrollment: 44
Study Start Date: October 2006
Study Completion Date: January 2010
Primary Completion Date: June 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (sunitinib malate)
Patients receive oral sunitinib malate once daily on days 1-28. Courses repeat every 42 days in the absence of disease progression or unacceptable toxicity.
Drug: sunitinib malate
Given orally
Other Names:
  • SU11248
  • sunitinib
  • Sutent

Detailed Description:

PRIMARY OBJECTIVES:

I. Assess the activity of sunitinib malate, in terms of rate of progression-free survival for ≥ 6 months and objective tumor response, in patients with recurrent or persistent leiomyosarcoma of the uterus who have received 1 or 2 prior cytotoxic therapies.

II. Determine the frequency and severity of adverse events.

SECONDARY OBJECTIVES:

I. Determine the duration of progression-free survival and overall survival.

OUTLINE: This is a multicenter study. Patients receive oral sunitinib malate once daily on days 1-28. Courses repeat every 42 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed every 3 months for 2 years and then every 6 months for 3 years.

PROJECTED ACCRUAL: A total of 44 patients will be accrued for this study.

  Eligibility

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

Inclusion Criteria:

  • Histologically confirmed leiomyosarcoma of the uterus

    • Recurrent or persistent disease
    • Refractory to curative therapy or established treatments
  • Measurable disease, defined as ≥ 1 unidimensionally measurable lesion ≥ 20 mm by conventional techniques or ≥ 10 mm by spiral CT scan

    • Ascites and pleural effusions are not considered measurable disease
  • Must have ≥ 1 target lesion to assess response

    • Tumors in a previously irradiated field are considered non-target lesions unless there is documented progression or biopsy-confirmed persistence ≥ 90 days after completion of radiotherapy
  • Received at least 1 but no more than 2 prior cytotoxic regimens

    • Initial treatment may have included high-dose chemotherapy, consolidation, or extended therapy administered after surgery or nonsurgical assessment
    • Cytotoxic regimens may have included any agent that targets the genetic and/or mitotic apparatus of dividing cells, resulting in dose-limiting toxicity to the bone marrow and/or gastrointestinal mucosa
  • Not a candidate for a higher priority GOG protocol
  • No known brain metastases
  • GOG performance status 0-2 (for patients who have received 1 prior regimen) OR GOG 0-1 (for patients who have received 2 prior regimens)
  • Absolute neutrophil count ≥ 1,500/mm³
  • Platelet count ≥ 100,000/mm³
  • Hemoglobin ≥ 9 g/dL
  • Creatinine ≤ 1.5 times upper limit of normal (ULN)
  • Bilirubin ≤ 1.5 times ULN
  • SGOT ≤ 2.5 times ULN
  • Alkaline phosphatase ≤ 1.5 times ULN
  • QTc < 500 msec
  • LVEF normal by echocardiogram
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception during and for ≥ 1 month after completion of study treatment
  • Patients with a pre-existing thyroid abnormality unable to maintain normal thyroid function with medication are not eligible
  • No significant EKG abnormalities (i.e., no history of serious ventricular arrhythmia OR EKG with ventricular tachycardia or ventricular fibrillation ≥ 3 beats in a row)
  • No sensory or motor neuropathy > grade 1
  • No NYHA class III-IV congestive heart failure

    • NYHA class II cardiac dysfunction allowed
    • History of NYHA class II heart failure that is asymptomatic on treatment allowed
  • No active infection requiring antibiotics
  • No other invasive malignancies within the past 5 years except for nonmelanoma skin cancer
  • No history of allergic reactions attributed to compounds of similar chemical or biologic composition to sunitinib malate
  • No poorly controlled hypertension (i.e., systolic blood pressure [BP] ≥ 140 mm Hg or diastolic BP ≥ 90 mm Hg)
  • No gastrointestinal tract disease resulting in an inability to take oral medication
  • No requirement for IV alimentation
  • No active peptic ulcer disease
  • No other condition that would impair ability to swallow and retain study drug
  • No serious or nonhealing wound, ulcer, or bone fracture
  • No abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 28 days
  • No cerebrovascular accident or transient ischemic attack within the past year
  • No myocardial infarction, cardiac arrhythmia, stable or unstable angina, or symptomatic congestive heart failure within the past year
  • No pulmonary embolism within the past year
  • No uncontrolled illness including, but not limited to, any of the following:

    • Ongoing or active infections
    • Psychiatric illness or social situations that would preclude study compliance
  • Recovered from prior surgery, chemotherapy, or radiotherapy
  • Prior anthracycline exposure and central thoracic radiation that included the heart allowed provided patient has New York Heart Association (NYHA) class II cardiac function
  • At least 1 week since prior hormonal therapy
  • At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas and mitomycin C) or radiotherapy
  • At least 4 weeks since prior major surgery
  • At least 3 years since prior radiotherapy for localized cancer of the breast, head and neck, or skin and no recurrent or metastatic disease
  • At least 3 years since prior adjuvant chemotherapy for localized cancer of the breast and no recurrent or metastatic disease
  • No prior radiotherapy to any portion of the abdominal cavity or pelvis unless for treatment of leiomyosarcoma
  • No prior chemotherapy to any portion of the abdominal cavity or pelvis unless for treatment of leiomyosarcoma
  • No prior noncytotoxic chemotherapy for recurrent or persistent disease
  • No prior surgical procedures affecting absorption
  • No coronary or peripheral artery bypass graft or stenting within the past year
  • No other prior antiangiogenic agents (e.g., bevacizumab, sorafenib, pazopanib, AZD2171, vatalanib, or vascular endothelial growth factor [VEGF] Trap)
  • No other prior cancer treatment that would preclude study treatment
  • At least 7 days since prior and no concurrent CYP3A4 inhibitors, including any of the following:

    • Azole fungals (e.g., ketoconazole or itraconazole)
    • Clarithromycin
    • Erythromycin
    • Diltiazem
    • Verapamil
    • HIV protease inhibitors (e.g., indinavir, saquinavir, ritonavir, atazanavir, or nelfinavir)
    • Delavirdine
  • At least 12 days since prior and no concurrent CYP3A4 inducers, including any of the following:

    • Rifampin
    • Rifabutin
    • Carbamazepine
    • Phenobarbital
    • Phenytoin
    • Hypericum perforatum (St. John's wort)
    • Efavirenz
    • Tipranavir
  • No concurrent proarrhythmic potential agent, including any of the following:

    • Terfenadine
    • Quinidine
    • Procainamide
    • Disopyramide
    • Sotalol
    • Probucol
    • Bepridil
    • Haloperidol
    • Risperidone
    • Indapamide
    • Flecainide
  • No concurrent therapeutic coumarin-derivative anticoagulants, such as warfarin

    • Doses ≤ 2 mg daily allowed for prophylaxis of thrombosis
    • Low molecular weight heparin allowed provided PT INR ≤ 1.5
  • No concurrent amifostine or other protective agents
  • No concurrent combination antiretroviral therapy for HIV-positive patients
  • No other concurrent investigational agents
  • No other concurrent anticancer agents or therapies
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00378911

Locations
United States, Pennsylvania
Gynecologic Oncology Group
Philadelphia, Pennsylvania, United States, 19103
Sponsors and Collaborators
Investigators
Principal Investigator: Martee Hensley Gynecologic Oncology Group
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00378911     History of Changes
Other Study ID Numbers: NCI-2012-02702, NCI-2012-02702, CDR0000495190, GOG-0231C, GOG-0231C, U10CA027469
Study First Received: September 19, 2006
Last Updated: June 11, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Leiomyosarcoma
Neoplasms, Muscle Tissue
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neoplasms
Sarcoma
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 September 18, 2014