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Endometrial AdenocarcinomaPhase 2NCT00888173

Brivanib Alaninate in Treating Patients With Recurrent or Persistent Endometrial Cancer

A Phase 2 study testing Brivanib Alaninate and Laboratory Biomarker Analysis in people with Endometrial Adenocarcinoma and Endometrial Clear Cell Adenocarcinoma, run by Gynecologic Oncology Group at 35 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older, women only
What is being tested?
Brivanib Alaninate and Laboratory Biomarker Analysis
Could I receive a placebo?
No, everyone receives an active treatment
How many people
45 participants
Where
35 sitesUnited States
Study dates
6 Jul 2009to 16 Jul 2016
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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
  • Absolute neutrophil count (ANC) greater than or equal to 1,500/mcl, equivalent to Common Terminology Criteria (CTCAE v3.0) grade 1
  • Platelets greater than or equal to 100,000/mcl
  • Hemoglobin > 9 g/dl
  • Creatinine less than or equal to 1.5 x institutional upper limit normal (ULN), CTCAE v3.0 grade 1
  • Urinalysis needs to be assessed at baseline and proteinuria must be less than or equal to 3+ by dipstick (CTCAE v3.0 grade 2 or less); if the urine dipstick is > 3+, a 24-hour protein level can be done, as clinically indicated by the investigator; the 24-hour protein level must be less than or equal to 3.5 g/24 hours (CTCAE v3.0 grade 2 or less)
  • Bilirubin less than or equal to 1.5 x ULN (CTCAE v3.0 grade 1)
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) less than or equal to 2.5 x ULN (CTCAE v3.0 grade 1)
  • Alkaline phosphatase less than or equal to 2.5 x ULN (CTCAE v3.0 grade 1)
  • Albumin greater than or equal to 2.5 g/dl
  • Neuropathy (sensory and motor) less than or equal to CTCAE v3.0 grade 1
  • Prothrombin time (PT) such that international normalized ratio (INR) is < 1.5 x ULN; patients on therapeutic warfarin are excluded from trial, anticoagulation with low molecular weight heparin is allowed
  • Patients must have signed an approved informed consent and authorization permitting release of personal health information
  • Patients must meet pre-entry requirements
  • Patients of childbearing potential must have a negative serum pregnancy test performed 48 hours prior to study entry and be practicing an effective form of contraception during the study and for at least 3 months after receiving the final treatment of brivanib
  • All patients must have a baseline electrocardiogram completed prior to study entry; baseline electrocardiogram (ECG) should be repeated if corrected QT interval (QTc) is found to be > 450 msec; QTc must NOT be > 450 msec on both ECGs performed during the same visit

Who cannot join

  • 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
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  • 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%
  • Patients with valvular heart disease >= CTCAE grade2
  • Patients with a serious uncontrolled medical disorder or active infection which would impair the ability of the subject to receive protocol therapy or whose control may be jeopardized by the complications of this therapy
  • Pre-existing thyroid abnormality with thyroid function that can not be maintained in the normal range with medication
  • Patients with hyponatremia (sodium < 130 mEq/L)
  • Patients with active/known human immunodeficiency virus (HIV), hepatitis B, or hepatitis C
  • Patients with known brain metastases
  • Patients who are pregnant or nursing
  • Patients with inability to swallow tablets or untreated malabsorption syndrome
  • Baseline serum potassium < 3.5 mmol/L (potassium supplementation may be given to restore the serum potassium above this level prior to entry study)
  • Patients on therapeutic warfarin anticoagulation will be excluded; patients converted to anticoagulation with a heparin compound will be allowed provided the patient?s PT is such that international normalized ratio (INR) is =< 1.5 x ULN

Trial locations and contacts

35 sites in 1 country.

35 sites in 1 country

United States35 sites

  • Abington Memorial Hospital

    Abington, Pennsylvania, 19001

  • McFarland Clinic PC-William R Bliss Cancer Center

    Ames, Iowa, 50010

  • University of Colorado Cancer Center - Anschutz Cancer Pavilion

    Aurora, Colorado, 80045

  • Rush University Medical Center

    Chicago, Illinois, 60612

  • MetroHealth Medical Center

    Cleveland, Ohio, 44109

  • Iowa Methodist Medical Center

    Des Moines, Iowa, 50309

  • Iowa-Wide Oncology Research Coalition NCORP

    Des Moines, Iowa, 50309

  • Medical Oncology and Hematology Associates-Des Moines

    Des Moines, Iowa, 50309

  • Medical Oncology and Hematology Associates-Laurel

    Des Moines, Iowa, 50314

  • Mercy Medical Center - Des Moines

    Des Moines, Iowa, 50314

  • Iowa Lutheran Hospital

    Des Moines, Iowa, 50316

  • Duke University Medical Center

    Durham, North Carolina, 27710

  • Spectrum Health at Butterworth Campus

    Grand Rapids, Michigan, 49503

  • Green Bay Oncology at Saint Vincent Hospital

    Green Bay, Wisconsin, 54301-3526

  • Saint Vincent Hospital Cancer Center Green Bay

    Green Bay, Wisconsin, 54301

  • Green Bay Oncology Limited at Saint Mary's Hospital

    Green Bay, Wisconsin, 54303

  • Saint Vincent Hospital and Health Care Center

    Indianapolis, Indiana, 46260

  • University of Iowa/Holden Comprehensive Cancer Center

    Iowa City, Iowa, 52242

  • Gundersen Lutheran Medical Center

    La Crosse, Wisconsin, 54601

  • North Shore University Hospital

    Manhasset, New York, 11030

  • The Hospital of Central Connecticut

    New Britain, Connecticut, 06050

  • Long Island Jewish Medical Center

    New Hyde Park, New York, 11040

  • North Shore-LIJ Health System/Center for Advanced Medicine

    New Hyde Park, New York, 11040

  • University of Oklahoma Health Sciences Center

    Oklahoma City, Oklahoma, 73104

  • Nebraska Methodist Hospital

    Omaha, Nebraska, 68114

  • Carilion Clinic Gynecological Oncology

    Roanoke, Virginia, 24016

  • Huntsman Cancer Institute/University of Utah

    Salt Lake City, Utah, 84112

  • Pacific Gynecology Specialists

    Seattle, Washington, 98104

  • Fred Hutchinson Cancer Research Center

    Seattle, Washington, 98109

  • Seattle Cancer Care Alliance

    Seattle, Washington, 98109

  • Swedish Medical Center-First Hill

    Seattle, Washington, 98122-4307

  • Northwest Hospital

    Seattle, Washington, 98133

  • University of Washington Medical Center

    Seattle, Washington, 98195

  • Washington University School of Medicine

    St Louis, Missouri, 63110

  • Oklahoma Cancer Specialists and Research Institute-Tulsa

    Tulsa, Oklahoma, 74146

Other trials in United States

About this study

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

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.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To assess the activity of brivanib (brivanib alaninate) for patients with recurrent or persistent endometrial cancer with the frequency of patients who survive progression-free for at least 6 months after initiating therapy or have objective tumor response..

SECONDARY OBJECTIVES:

  1. To determine the duration of progression-free survival and overall survival. II. To determine the nature and degree of toxicity of brivanib as assessed by Common Terminology Criteria for Adverse Events (CTCAE) version (v)3.0 in this cohort of patients.

TERTIARY OBJECTIVES:

  1. To determine whether activating mutations in fibroblast growth factor receptor 2 (FGFR2) are associated with progression-free survival status > 6 months following brivanib treatment, objective tumor response following brivanib treatment, or endometrioid histology.

II. To explore the associations between select biomarkers and response to brivanib (progression-free survival status > 6 months and objective tumor response), measures of clinical outcome (progression-free survival and overall survival) or disease status including histologic cell type: i) mutations in FGFR2 or phosphatase and tensin homolog (PTEN) in deoxyribonucleic acid (DNA) from formalin-fixed and paraffin-embedded (FFPE) tumor or normal blood cells; ii) immunohistochemical (IHC) expression of the FGFR family and ligands, steroid receptor isoforms or phosphorylated (p) v-akt murine thymoma viral oncogene homolog 1 (AKT) in FFPE tumor; iii) concentration or the change in the concentration of vascular endothelial growth factor (VEGF) or type IV collagen in pre-cycle 1, pre-cycle 2 and/or pre-cycle 3 plasma.

III. To explore the relationship among the panel of biomarkers evaluated in this cohort: i) mutations in FGFR2 or PTEN; ii) IHC expression of the FGFR family and ligands, steroid receptor isoforms or pAKT; iii) concentration or the change in the concentration of VEGF or type IV collagen.

OUTLINE:

Patients receive brivanib alaninate orally (PO) once daily (QD) 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 up every 3 months for 2 years and then every 6 months for 3 years.

Being tested
Brivanib Alaninate, Laboratory Biomarker Analysis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Brivanib AlaninateDrug

    Given PO

  • Laboratory Biomarker AnalysisOther

    Correlative studies

Study groups in NCT00888173
Study groupRoleWhat they receive
Treatment (brivanib alaninate)ExperimentalPatients receive brivanib alaninate PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Receives: Drug: Brivanib Alaninate; Other: Laboratory Biomarker Analysis

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Progression-free Survival > 6 Months

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

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

  2. 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.

    Measured: 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)

  1. Duration of Overall Survival

    Characterized graphically with Kaplan-Meier estimates and using descriptive statistics. The effect of cell type (type I versus type II endometrial cancers) on overall survival will be examined.

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

  2. Duration of Progression-free Survival

    Characterized graphically with Kaplan-Meier estimates and using descriptive statistics. The effect of cell type (type I versus type II endometrial cancers) on progression-free survival will be examined.

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

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

    Adverse Events (grade 3 or higher)

    Measured: Up to 5 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted27 Apr 2009 (estimated)
  2. Study start6 Jul 2009
  3. Primary completion16 Jul 2016
  4. Study completion16 Jul 2016

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
45 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00888173
Sponsor's protocol ID
GOG-0229I
Other IDs
NCI-2011-01918, CA182-029, CDR0000641191, GOG-0229I, GOG-0229I, U10CA180868, U10CA027469
Status last verified
Aug 2017
First submitted
24 Apr 2009
Last updated
6 Dec 2017
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Brivanib Alaninate and Laboratory Biomarker Analysis in people with Endometrial Adenocarcinoma and Endometrial Clear Cell Adenocarcinoma, run by Gynecologic Oncology Group at 35 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 30 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 6 Dec 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 35 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 6 Nov 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Progression-free Survival > 6 Months (time frame: For patients whose disease can be evaluated by physical examination, progression was assessed prior to each cycle for 6 months.). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00888173.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Dec 2017.

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