Brivanib Alaninate in Treating Patients With Recurrent or Persistent Endometrial Cancer

NCT00888173 | Completed Phase 2 Results DMC

• 6 other identifiers: GOG-0229INCI-2011-01918CA182-029CDR0000641191U10CA180868U10CA027469
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 35

Brief Summary

This phase II trial is studying how well brivanib alaninate works in treating patients with endometrial cancer that has come back (recurred) or is persistent. 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.

Conditions

Endometrial Adenocarcinoma; Endometrial Clear Cell Adenocarcinoma; Endometrial Mixed Adenocarcinoma; Endometrial Mucinous Adenocarcinoma; Endometrial Serous Adenocarcinoma; Endometrial Squamous Cell Carcinoma; Endometrial Transitional Cell Carcinoma; Endometrial Undifferentiated Carcinoma; Recurrent Uterine Corpus Carcinoma

Outcome Measures

Primary Outcomes (2)

• Progression-free Survival > 6 Months

  Whether or not the patient survived progression-free for at least 6 months.

  For patients whose disease can be evaluated by physical examination, progression was assessed prior to each cycle for 6 months.

• Tumor Response

  Per response evaluation criteria in Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>= 30 % decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR+PR.

  If evaluated by physical exam, response was assessed prior to each cycle. If evaluated by CT or MRI, response was assessed during course of therapy. Overall time frame is up to 6 months.

Secondary Outcomes (3)

• Duration of Overall Survival

  From entry into the study to death or the date of last contact, assessed up to 5 years

• Duration of Progression-free Survival

  Form study entry until disease progression, death or date of last contact, assessed up to 5 years

• Severity of Adverse Events as Assessed by CTCAE v3.0 Criteria

  Up to 5 years

Other Outcomes (4)

• Activating Mutation in FGFR2

  Up to 5 years

• Change in Concentration of VEGF and Type IV Collagen

  Baseline to up to pre-course 3

• IHC Expression of FGFR Family and Ligands, Steroid Receptor Isoforms, and pAKT

  Up to 5 years

Study Arms (1)

Treatment (brivanib alaninate)

EXPERIMENTAL

Patients receive brivanib alaninate PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Drug: Brivanib Alaninate; Other: Laboratory Biomarker Analysis

Interventions

Brivanib Alaninate DRUG

Given PO

Treatment (brivanib alaninate)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (brivanib alaninate)

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have recurrent or persistent endometrial carcinoma, which is refractory to curative therapy or established treatments; histologic confirmation of the original primary tumor is required
• Patients with the following histologic epithelial cell types are eligible: endometrioid adenocarcinoma, serous adenocarcinoma, undifferentiated carcinoma, clear cell adenocarcinoma, mixed epithelial carcinoma, adenocarcinoma not otherwise specified (N.O.S.), mucinous adenocarcinoma, squamous cell, and transitional cell carcinoma
• All patients must have measurable disease; measurable disease is defined as at least one lesion that can be accurately measured in at least one dimension (longest dimension to be recorded); each lesion must be \>= 20 mm when measured by conventional techniques, including palpation, plain x-ray, computed tomography (CT), and magnetic resonance imaging (MRI), or \>= 10 mm when measured by spiral CT
• Patients must have at least one ?target lesion? to be used to assess response on this protocol as defined by Response Evaluation Criteria in Solid Tumors (RECIST); tumors within a previously irradiated field will be designated as ?non-target? lesions unless progression is documented or a biopsy is obtained to confirm persistence at least 90 days following completion of radiation therapy
• Patients must not be eligible for a higher priority Gynecologic Oncology Group (GOG) protocol, if one exists; in general, this would refer to any active GOG Phase III or Rare Tumor protocol for the same patient population
• Patients who have received one prior regimen must have a GOG performance status of 0, 1, or 2; patients who have received two prior regimens must have a GOG performance status of 0 or 1
• Recovery from effects of recent surgery, radiotherapy, or chemotherapy
• Patients should be free of active infection requiring antibiotics (with the exception of uncomplicated urinary tract infection \[UTI\])
• Any hormonal therapy directed at the malignant tumor must be discontinued at least one week prior to registration
• Any other prior therapy directed at the malignant tumor, including immunologic agents, must be discontinued at least three weeks prior to registration
• Patients must have had one 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
• Patients are allowed to receive, but are not required to receive, one additional cytotoxic regimen for management of recurrent or persistent endometrial disease according to the following definition:
• Cytotoxic regimens include 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
• Note: Patients on this non-cytotoxic study are allowed to receive one additional cytotoxic chemotherapy regimen for management of recurrent or persistent endometrial disease, as defined above; however, patients are encouraged to enroll on second-line non-cytotoxic studies prior to receiving additional cytotoxic therapy
• Patients must NOT have received any non-cytotoxic therapy for management of endometrial cancer with the exception of hormonal therapy

You may not qualify if:

• Patients who have had prior therapy with brivanib or anti-vascular, anti-PDGFR (platelet-derived growth factor receptor) or anti-FGFR (fibroblast growth factor receptor) therapy
• Patients with a history of other invasive malignancies, with the exception of non-melanoma skin cancer and other specific malignancies as noted below, are excluded if there is any evidence of the other malignancy being present within the last three years; patients are also excluded if their previous cancer treatment contraindicates this protocol therapy
• Patients who have received prior radiotherapy to any portion of the abdominal cavity or pelvis OTHER THAN for the treatment of endometrial cancer within the last three years are excluded; prior radiation for localized cancer of the breast, head and neck, or skin is permitted, provided that it was completed more than three years prior to registration, and the patient remains free of recurrent or metastatic disease
• Patients who have received prior chemotherapy for any abdominal or pelvic tumor OTHER THAN for the treatment of endometrial cancer within the last three years are excluded; patients may have received prior adjuvant chemotherapy for localized breast cancer, provided that it was completed more than three years prior to registration, and that the patient remains free of recurrent or metastatic disease
• Patients that are on required chronic anti-platelet therapy (aspirin \> 300 mg/day, or clopidogrel greater than or equal to 75 mg/day)
• Patients with gastrointestinal bleeding or any other hemorrhage/bleeding event CTCAE grade \>= 3 within 30 days prior to study entry
• Patients with a history of poor wound healing, non healing ulcers or bone fractures within the last 3 months
• Patients with uncontrolled or significant cardiovascular disease including:
• Myocardial infarction within 12 months
• Uncontrolled angina within 12 months
• Class III-IV New York Heart Association (NYHA) congestive heart failure
• Uncontrolled hypertension (systolic blood pressure \[BP\] \> 150 or diastolic BP \> 100 mmHg for 24 hours) despite optimized anti-hypertensive therapy; BP must be below 150/100 mmHg at screening; subjects with a history of hypertension who are receiving treatment with calcium channel blockers that are cytochrome P450 family 3, subfamily A, polypeptide 4 (CYP3A4) inhibitors should be changed to an alternative antihypertensive medication before study entry
• History of stroke, transient ischemic attack (TIA), or other central nervous system (CNS) ischemic event
• Cardiac arrhythmias requiring anti-arrhythmic therapy other than beta blockers or digoxin
• Patients must have pre-therapy left ventricle ejection fraction (LVEF) testing and have an ejection fraction \> 50%

Sponsors & Collaborators

• Gynecologic Oncology Group: lead
• National Cancer Institute (NCI): collaborator

Study Sites (35)

University of Colorado Cancer Center - Anschutz Cancer Pavilion

Aurora, Colorado, 80045, United States

Location

The Hospital of Central Connecticut

New Britain, Connecticut, 06050, United States

Location

Rush University Medical Center

Chicago, Illinois, 60612, United States

Location

Saint Vincent Hospital and Health Care Center

Indianapolis, Indiana, 46260, United States

Location

McFarland Clinic PC-William R Bliss Cancer Center

Ames, Iowa, 50010, United States

Location

Iowa Methodist Medical Center

Des Moines, Iowa, 50309, United States

Location

Iowa-Wide Oncology Research Coalition NCORP

Des Moines, Iowa, 50309, United States

Location

Medical Oncology and Hematology Associates-Des Moines

Des Moines, Iowa, 50309, United States

Location

Medical Oncology and Hematology Associates-Laurel

Des Moines, Iowa, 50314, United States

Location

Mercy Medical Center - Des Moines

Des Moines, Iowa, 50314, United States

Location

Iowa Lutheran Hospital

Des Moines, Iowa, 50316, United States

Location

University of Iowa/Holden Comprehensive Cancer Center

Iowa City, Iowa, 52242, United States

Location

Spectrum Health at Butterworth Campus

Grand Rapids, Michigan, 49503, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Nebraska Methodist Hospital

Omaha, Nebraska, 68114, United States

Location

North Shore University Hospital

Manhasset, New York, 11030, United States

Location

Long Island Jewish Medical Center

New Hyde Park, New York, 11040, United States

Location

North Shore-LIJ Health System/Center for Advanced Medicine

New Hyde Park, New York, 11040, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

MetroHealth Medical Center

Cleveland, Ohio, 44109, United States

Location

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, 73104, United States

Location

Oklahoma Cancer Specialists and Research Institute-Tulsa

Tulsa, Oklahoma, 74146, United States

Location

Abington Memorial Hospital

Abington, Pennsylvania, 19001, United States

Location

Huntsman Cancer Institute/University of Utah

Salt Lake City, Utah, 84112, United States

Location

Carilion Clinic Gynecological Oncology

Roanoke, Virginia, 24016, United States

Location

Pacific Gynecology Specialists

Seattle, Washington, 98104, United States

Location

Fred Hutchinson Cancer Research Center

Seattle, Washington, 98109, United States

Location

Seattle Cancer Care Alliance

Seattle, Washington, 98109, United States

Location

Swedish Medical Center-First Hill

Seattle, Washington, 98122-4307, United States

Location

Northwest Hospital

Seattle, Washington, 98133, United States

Location

University of Washington Medical Center

Seattle, Washington, 98195, United States

Location

Green Bay Oncology at Saint Vincent Hospital

Green Bay, Wisconsin, 54301-3526, United States

Location

Saint Vincent Hospital Cancer Center Green Bay

Green Bay, Wisconsin, 54301, United States

Location

Green Bay Oncology Limited at Saint Mary's Hospital

Green Bay, Wisconsin, 54303, United States

Location

Gundersen Lutheran Medical Center

La Crosse, Wisconsin, 54601, United States

Location

MeSH Terms

Interventions

brivanib

Results Point of Contact

• Title: Linda Gedeon For Michael Sill, PhD.
• Organization: NRG Oncology

lgedeon@gogstats.org

716-845-1169

Study Officials

• Matthew Powell

  NRG Oncology

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 24, 2009
• First Posted: April 27, 2009
• Study Start: July 6, 2009
• Primary Completion: July 16, 2016
• Study Completion: July 16, 2016
• Last Updated: December 6, 2017
• Results First Posted: November 6, 2017

Record last verified: 2017-08

Locations

US (35)