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Brivanib Alaninate in Treating Patients With Recurrent or Persistent Endometrial Cancer

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Gynecologic Oncology Group
ClinicalTrials.gov Identifier:
NCT00888173
First received: April 24, 2009
Last updated: August 8, 2014
Last verified: August 2014
  Purpose

This phase II trial is studying how well brivanib alaninate works in treating patients with recurrent or persistent endometrial cancer. Brivanib alaninate 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 Clear Cell Carcinoma
Recurrent Endometrial Carcinoma
Drug: brivanib alaninate
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 Brivanib (BMS582664), an Oral, Multitargeted Growth Factor Tyrosine Kinase Inhibitor in the Treatment of Recurrent or Persistent Endometrial Carcinoma

Resource links provided by NLM:


Further study details as provided by Gynecologic Oncology Group:

Primary Outcome Measures:
  • Progression free survival [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Objective tumor response defined by RECIST [ Time Frame: 6 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Progression-free survival [ Time Frame: Form study entry until disease progression, death or date of last contact, assessed up to 5 years ] [ Designated as safety issue: No ]
    Characterized graphically with Kaplan-Meier estimates and using descriptive statistics.

  • 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 with Kaplan-Meier estimates and using descriptive statistics.

  • Frequency of adverse effects defined as any unfavorable and unintended sign, symptom, or disease that occurs in a patient administered a medical treatment, whether the event is considered related or unrelated to the medical treatment [ Time Frame: Up to 5 years ] [ Designated as safety issue: Yes ]
  • Severity of adverse events as assessed by CTCAE v3.0 criteria [ Time Frame: Up to 5 years ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 43
Study Start Date: July 2009
Estimated Primary Completion Date: January 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (brivanib alaninate)
Patients receive oral brivanib alaninate once daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Drug: brivanib alaninate
Given orally
Other Name: BMS-582664

Detailed Description:

PRIMARY OBJECTIVES:

I. To assess the activity of brivanib alaninate, in terms of 6-month progression-free survival (PFS) and objective tumor response, in patients with recurrent or persistent endometrial carcinoma.

SECONDARY OBJECTIVES:

I. To determine the duration of PFS and overall survival of these patients. II. To determine the nature and degree of toxicity of brivanib alaninate in these patients as assessed by CTCAE v3.0.

OUTLINE: This is a multicenter study.

Patients receive oral brivanib alaninate once daily on days 1-28. Courses repeat every 28 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.

  Eligibility

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

Inclusion Criteria:

  • Histologically confirmed endometrial carcinoma, including any of the following epithelial cell types:

    • Endometrioid adenocarcinoma
    • Serous adenocarcinoma
    • Undifferentiated carcinoma
    • Clear cell adenocarcinoma
    • Mixed epithelial carcinoma
    • Adenocarcinoma not otherwise specified
    • Mucinous adenocarcinoma
    • Squamous cell carcinoma
    • Transitional cell carcinoma
  • Recurrent or persistent disease that is refractory to curative therapy or established treatments
  • Measurable disease, defined as ≥ 1 unidimensionally measurable lesion ≥ 20 mm by conventional techniques (e.g., palpation, plain x-ray, CT scan, or MRI) or ≥ 10 mm by spiral CT scan
  • Must have ≥ 1 target lesion to assess response as defined by RECIST criteria

    • Tumors within a previously irradiated field will be designated as "non-target" lesions unless there is documented disease progression or a biopsy is obtained to confirm persistence ≥ 90 days after completion of radiotherapy
  • Must not be eligible for a higher priority GOG protocol, if one exists
  • Must have received 1 prior chemotherapeutic regimen for management of endometrial carcinoma

    • Chemotherapy administered in conjunction with primary radiation as a radio-sensitizer will be counted as a systemic chemotherapy regimen
    • One additional cytotoxic regimen for management of recurrent or persistent disease allowed
  • No known brain metastases
  • GOG performance status (PS) 0-2 (for patients who have received 1 prior regimen) OR GOG PS 0-1 (for patients who have received 2 prior regimens)
  • ANC ≥ 1,500/mcL
  • Platelet count ≥ 100,000/mcL
  • Hemoglobin > 9 g/dL
  • Creatinine ≤ 1.5 times upper limit of normal (ULN)

    • Urine protein: proteinuria must be ≤ 3+ by dipstick
    • Patients with urine protein > 3+ who undergo a 24 hour urine collection and demonstrate ≤ 3.5 g in 24 h allowed
  • Bilirubin ≤ 1.5 times ULN
  • AST/ALT ≤ 2.5 times ULN
  • Alkaline phosphatase ≤ 2.5 times ULN
  • Albumin ≥ 2.5 g/dL
  • PT/INR ≤ 1.5 times ULN
  • Baseline serum potassium ≥ 3.5 mmol/L (potassium supplementation allowed)
  • QTc ≤ 450 msec by ECG
  • LVEF > 50%
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception during and for ≥ 3 months after completion of study treatment
  • No pre-existing thyroid abnormality with thyroid function that cannot be maintained in the normal range with medication
  • No neuropathy (sensory and motor) > grade 1 (per CTCAE v3.0 criteria)
  • No hyponatremia (i.e., sodium < 130 mEq/L)
  • No active/known HIV, hepatitis B, or hepatitis C
  • No gastrointestinal bleeding or any other hemorrhage/bleeding event ≥ grade 3 (per CTCAE v3.0 criteria) within the past 30 days
  • No poor wound healing, non-healing ulcers, or bone fractures within the past 3 months
  • No uncontrolled or significant cardiovascular disease, including any of the following:

    • Myocardial infarction within the past 12 months
    • Uncontrolled angina within the past 12 months
    • NYHA class III-IV congestive heart failure
    • Uncontrolled hypertension, defined as systolic blood pressure (BP) > 150 mm Hg or diastolic BP > 100 mm Hg, despite optimized antihypertensive therapy
    • History of stroke, transient ischemic attack, or other CNS ischemic event
    • Cardiac arrhythmias requiring antiarrhythmic therapy, except beta blockers or digoxin
    • Valvular heart disease ≥ grade 2 (per CTCAE v3.0 criteria)
  • No active infection requiring antibiotics, except uncomplicated urinary tract infection
  • No inability to swallow tablets or untreated malabsorption syndrome
  • No serious uncontrolled medical disorder or active infection that would impair the ability of the patient to receive study therapy or whose control may be jeopardized by the complications of this therapy
  • No other invasive malignancies within the past 3 years, except nonmelanoma skin cancer or other specific malignancies
  • Concurrent low molecular weight heparin allowed provided PT/INR ≤ 1.5
  • Recovered from prior surgery, radiotherapy, or chemotherapy
  • At least 1 week since prior hormonal therapy directed at the malignant tumor
  • At least 3 weeks since prior immunologic agents or other therapy directed at the malignant tumor
  • No prior non-cytotoxic therapy for management of endometrial carcinoma, except hormonal therapy
  • No prior brivanib alaninate or other anti-vascular, anti-PDGFR, or anti-FGFR therapy
  • No prior radiotherapy to any portion of the abdominal cavity or pelvis, except for the treatment of endometrial carcinoma within the past 5 years

    • Prior radiotherapy for localized cancer of the breast, head and neck, or skin allowed provided it was completed > 3 years ago and the patient remains free of recurrent or metastatic disease
  • No prior chemotherapy for any abdominal or pelvic tumor, except for the treatment of endometrial carcinoma within the past 5 years

    • Prior adjuvant chemotherapy for localized breast cancer allowed provided it was completed > 3 years ago and the patient remains free of recurrent or metastatic disease
  • No prior cancer treatment that would contraindicate study therapy
  • No concurrent chronic antiplatelet therapy (e.g., aspirin > 300 mg/day or clopidogrel ≥ 75 mg/day)
  • No concurrent warfarin for prophylaxis or treatment of thrombosis allowed

    • Low-molecular weight heparin allowed
  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: NCT00888173

  Show 35 Study Locations
Sponsors and Collaborators
Gynecologic Oncology Group
Investigators
Principal Investigator: Matthew Powell Gynecologic Oncology Group
  More Information

No publications provided

Responsible Party: Gynecologic Oncology Group
ClinicalTrials.gov Identifier: NCT00888173     History of Changes
Other Study ID Numbers: GOG-0229I, NCI-2011-01918, GOG-0229I, CDR0000641191, GOG-0229I, GOG-0229I, U10CA027469
Study First Received: April 24, 2009
Last Updated: August 8, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Adenocarcinoma
Adenocarcinoma, Clear Cell
Adenomyoepithelioma
Carcinoma
Endometrial Neoplasms
Uterine Neoplasms
Genital Diseases, Female
Genital Neoplasms, Female
Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Complex and Mixed
Neoplasms, Glandular and Epithelial
Urogenital Neoplasms
Uterine Diseases

ClinicalTrials.gov processed this record on November 20, 2014