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A Phase II Evaluation of Brivanib (BMS582664), an Oral, Multitargeted Growth Factor Tyrosine Kinase Inhibitor in the Treatment of Recurrent or Persistent Endometrial Carcinoma


Phase 2
18 Years
N/A
Open (Enrolling)
Female
Endometrial Cancer

Thank you

Trial Information

A Phase II Evaluation of Brivanib (BMS582664), an Oral, Multitargeted Growth Factor Tyrosine Kinase Inhibitor in the Treatment of Recurrent or Persistent Endometrial Carcinoma


OBJECTIVES:

Primary

- 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

- To determine the duration of PFS and overall survival of these patients.

- 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.

Inclusion Criteria


DISEASE CHARACTERISTICS:

- 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

PATIENT CHARACTERISTICS:

- 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

PRIOR CONCURRENT THERAPY:

- See Disease Characteristics

- 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

- Concurrent low molecular weight heparin allowed provided PT/INR ≤ 1.5

Type of Study:

Interventional

Study Design:

Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Frequency of patients with progression-free survival (PFS) for ≥ 6 months or objective tumor response

Safety Issue:

No

Principal Investigator

Matthew A. Powell, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Washington University Siteman Cancer Center

Authority:

United States: Federal Government

Study ID:

CDR0000641191

NCT ID:

NCT00888173

Start Date:

August 2009

Completion Date:

Related Keywords:

  • Endometrial Cancer
  • recurrent endometrial carcinoma
  • endometrial adenocarcinoma
  • endometrial clear cell carcinoma
  • Endometrial Neoplasms
  • Sarcoma, Endometrial Stromal
  • Adenoma

Name

Location

Fred Hutchinson Cancer Research CenterSeattle, Washington  98109
Duke Comprehensive Cancer CenterDurham, North Carolina  27710
CCOP - Iowa Oncology Research AssociationDes Moines, Iowa  50309-1016
George Bray Cancer Center at the Hospital of Central Connecticut - New Britain CampusNew Britain, Connecticut  06050
Case Comprehensive Cancer CenterCleveland, Ohio  44106-5065
MetroHealth Cancer Care Center at MetroHealth Medical CenterCleveland, Ohio  44109
Rush University Medical CenterChicago, Illinois  60612-3824
Holden Comprehensive Cancer Center at University of IowaIowa City, Iowa  52242-1002
Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical CenterLebanon, New Hampshire  03756-0002
Cleveland Clinic Taussig Cancer CenterCleveland, Ohio  44195
Fletcher Allen Health Care - University Health Center CampusBurlington, Vermont  05401
John Stoddard Cancer Center at Iowa Methodist Medical CenterDes Moines, Iowa  50309
Swedish Cancer Institute at Swedish Medical Center - First Hill CampusSeattle, Washington  98104
Carilion Gynecologic Oncology AssociatesRoanoke, Virginia  24014
Long Island Jewish Medical CenterNew Hyde Park, New York  11040
St. Vincent Hospital Regional Cancer CenterGreen Bay, Wisconsin  54307-3508
Green Bay Oncology, Limited at St. Vincent Hospital Regional Cancer CenterGreen Bay, Wisconsin  54301-3526
Green Bay Oncology, Limited at St. Mary's HospitalGreen Bay, Wisconsin  54303
University Cancer Center at University of Washington Medical CenterSeattle, Washington  98195
Siteman Cancer Center at Barnes-Jewish Hospital - Saint LouisSt. Louis, Missouri  63110
Don Monti Comprehensive Cancer Center at North Shore University HospitalManhasset, New York  11030
Oklahoma University Cancer InstituteOklahoma City, Oklahoma  73104
Gundersen Lutheran Center for Cancer and BloodLa Crosse, Wisconsin  54601
Methodist Estabrook Cancer CenterOmaha, Nebraska  68114-4199
Huntsman Cancer Institute at University of UtahSalt Lake City, Utah  84112
Cleveland Clinic Cancer Center at Fairview HospitalCleveland, Ohio  44111
Hillcrest Cancer Center at Hillcrest HospitalMayfield Heights, Ohio  44124
Cancer Care Associates - Saint Francis CampusTulsa, Oklahoma  74136-1929
Rosenfeld Cancer Center at Abington Memorial HospitalAbington, Pennsylvania  19001
Morgan Cancer Center at Lehigh Valley Hospital - Cedar CrestAllentown, Pennsylvania  18105
John Stoddard Cancer Center at Iowa Lutheran HospitalDes Moines, Iowa  50316-2301
Medical Oncology and Hematology Associates at John Stoddard Cancer CenterDes Moines, Iowa  50309
Medical Oncology and Hematology Associates at Mercy Cancer CenterDes Moines, Iowa  50314
Mercy Cancer Center at Mercy Medical Center - Des MoinesDes Moines, Iowa  50314
David L. Rike Cancer Center at Miami Valley HospitalDayton, Ohio  45409
McFarland Clinic, PCAmes, Iowa  50010
Monter Cancer Center of the North Shore-LIJ Health SystemLake Success, New York  11042
Summa Center for Cancer Care at Akron City HospitalAkron, Ohio  44309-2090
McGlinn Family Regional Cancer Center at Reading Hospital and Medical CenterReading, Pennsylvania  19612-6052
Seattle Cancer Care AllianceSeattle, Washington  98109
Pacific Gynecology SpecialistsSeattle, Washington  98104
University of Colorado Cancer Center at UC Health Sciences CenterAurora, Colorado  80045
Northwest Hospital and Medical CenterSeattle, Washington  98133
Black Hills Obstetrics & Gynecology LLPRapid City, South Dakota  57701
St. Vincent Oncology CenterIndianapolis, Indiana  46260