AzTrials
AzTrials

Cervical AdenocarcinomaPhase 2NCT01267253

Brivanib Alaninate in Treating Patients With Persistent or Recurrent Cervical Cancer

A Phase 2 study testing Brivanib Alaninate and Laboratory Biomarker Analysis in people with Cervical Adenocarcinoma and Cervical Adenosquamous Carcinoma, run by Gynecologic Oncology Group at 43 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 studies how well brivanib alaninate works in treating patients with cervical cancer that has come back. Brivanib alaninate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth or 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
31 participants
Where
43 sitesUnited States
Study dates
4 Apr 2011to 28 Feb 2014
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 persistent or recurrent squamous cell carcinoma, adenosquamous carcinoma, adenocarcinoma, or non-squamous cell carcinoma of the cervix with documented disease progression (disease not amenable to curative therapy); histologic confirmation of the original primary tumor is required via the pathology report
  • All patients must have measurable disease, defined by Response Evaluation Criteria In Solid Tumors (RECIST 1.1); measurable disease is defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded); each lesion must be >= 10 mm when measured by computed tomography (CT), magnetic resonance imaging (MRI) or caliper measurement by clinical exam; or >= 20 mm when measured by chest x-ray; lymph nodes must be >= 15 mm in short axis when measured by CT or MRI
  • Patient must have at least one ?target lesion? to be used to assess response on this protocol as defined by RECIST 1.1
  • 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 protocol or rare tumor protocol for the same patient population
Show all 35Show fewer
  • 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 chemotherapy and immunologic agents, must be discontinued at least three weeks prior to registration
  • Any prior radiation therapy must be completed at least 4 weeks prior to registration
  • At least 4 weeks must have elapsed from the time of any major surgical procedure
  • Patients must have had one prior systemic chemotherapeutic regimen for management of advanced, metastatic, or recurrent carcinoma of the cervix; chemotherapy administered concurrent with primary radiation (e.g.; weekly cisplatin) is not counted as a systemic chemotherapy regimen for management of advanced, metastatic, or recurrent disease; adjuvant chemotherapy given following the completion of radiation therapy (or concurrent chemotherapy and radiation therapy) is not counted as a systemic chemotherapy regimen for management of advanced, metastatic, or recurrent disease (e.g.; paclitaxel and carboplatin for up to 4 cycles)
  • Patients are allowed to receive, but are not required to receive, one additional cytotoxic regimen for management of recurrent or persistent disease
  • Patients must have NOT received any non-cytotoxic (biologic or targeted) agents as part of their primary treatment or for management of recurrent or persistent disease
  • Non-cytotoxic (biologic or targeted) agents include (but are not limited to) monoclonal antibodies, cytokines, and small-molecule inhibitors of signal transduction
  • Absolute neutrophil count (ANC) greater than or equal to 1,500/mcl
  • 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 of normal (ULN)
  • Urinalysis needs to be assessed at baseline and proteinuria must be less than or equal to 2+ by dipstick
  • If the urine dipstick is > 2+, 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
  • Bilirubin less than or equal to 1.5 x ULN
  • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) less than or equal to 3 x ULN
  • Alkaline phosphatase less than or equal to 2.5 x ULN
  • Albumin greater than or equal to 2.5 g/dl
  • Neuropathy (sensory and motor) less than or equal to 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 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, 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 cervical 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 cervical 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
Show all 30Show fewer
  • 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 >= grade 3 of the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) 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 any of the following:
  • Myocardial infarction within 12 months
  • Uncontrolled angina within 12 months
  • Class III-IV New York Heart Association (NYHA) congestive heart failure
  • Uncontrolled hypertension despite anti-hypertensive therapy
  • Blood pressure (BP) must be less than or equal to 140/90 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 ventricular ejection fraction (LVEF) testing and have an ejection fraction >= institutional lower limit of normal (LLN)
  • Patients with valvular heart disease >= grade 2
  • 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 cannot 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; HIV-positive subjects on combination antiretroviral therapy are ineligible
  • Patients with known brain metastases
  • Patients who are pregnant or nursing
  • Patients with inability to swallow tablets or untreated malabsorption syndrome
  • Patients with 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 are excluded
  • Patients converted to anticoagulation with low molecular weight heparin will be allowed provided the patient?s PT is such that INR is =< 1.5 x ULN

Trial locations and contacts

43 sites in 1 country.

43 sites in 1 country

United States43 sites

  • Abington Memorial Hospital

    Abington, Pennsylvania, 19001

  • Summa Akron City Hospital/Cooper Cancer Center

    Akron, Ohio, 44304

  • Michigan Cancer Research Consortium NCORP

    Ann Arbor, Michigan, 48106

  • Saint Joseph Mercy Hospital

    Ann Arbor, Michigan, 48106

  • Greater Baltimore Medical Center

    Baltimore, Maryland, 21204

  • Providence Saint Joseph Medical Center/Disney Family Cancer Center

    Burbank, California, 91505

  • Cooper Hospital University Medical Center

    Camden, New Jersey, 08103

  • Carolinas Medical Center/Levine Cancer Institute

    Charlotte, North Carolina, 28203

  • Rush University Medical Center

    Chicago, Illinois, 60612

  • University of Chicago Comprehensive Cancer Center

    Chicago, Illinois, 60637

  • Case Western Reserve University

    Cleveland, Ohio, 44106

  • Riverside Methodist Hospital

    Columbus, Ohio, 43214

  • Union Hospital of Cecil County

    Elkton, Maryland, 21921

  • Baylor All Saints Medical Center at Fort Worth

    Fort Worth, Texas, 76104

  • Smilow Cancer Hospital Care Center at Saint Francis

    Hartford, Connecticut, 06105

  • Sudarshan K Sharma MD Limited-Gynecologic Oncology

    Hinsdale, Illinois, 60521

  • Lyndon Baines Johnson General Hospital

    Houston, Texas, 77026-1967

  • M D Anderson Cancer Center

    Houston, Texas, 77030

  • Saint Vincent Hospital and Health Care Center

    Indianapolis, Indiana, 46260

  • University of Mississippi Medical Center

    Jackson, Mississippi, 39216

  • Kettering Medical Center

    Kettering, Ohio, 45429

  • Women's Cancer Center of Nevada

    Las Vegas, Nevada, 89169

  • Beebe Medical Center

    Lewes, Delaware, 19958

  • Saint Mary Mercy Hospital

    Livonia, Michigan, 48154

  • University of Wisconsin Hospital and Clinics

    Madison, Wisconsin, 53792

  • UH Seidman Cancer Center at Lake Health Mentor Campus

    Mentor, Ohio, 44060

  • The Hospital of Central Connecticut

    New Britain, Connecticut, 06050

  • Christiana Care Health System-Christiana Hospital

    Newark, Delaware, 19718

  • University of Oklahoma Health Sciences Center

    Oklahoma City, Oklahoma, 73104

  • Nebraska Methodist Hospital

    Omaha, Nebraska, 68114

  • Florida Hospital Orlando

    Orlando, Florida, 32803

  • Saint Joseph's Hospital and Medical Center

    Phoenix, Arizona, 85013

  • West Penn Hospital

    Pittsburgh, Pennsylvania, 15224

  • Saint Joseph Mercy Oakland

    Pontiac, Michigan, 48341

  • Lake Huron Medical Center

    Port Huron, Michigan, 48060

  • Women and Infants Hospital

    Providence, Rhode Island, 02905

  • Virginia Commonwealth University/Massey Cancer Center

    Richmond, Virginia, 23298

  • UCSF Medical Center-Mount Zion

    San Francisco, California, 94115

  • Sarasota Memorial Hospital

    Sarasota, Florida, 34239

  • Memorial Health University Medical Center

    Savannah, Georgia, 31404

  • Baystate Medical Center

    Springfield, Massachusetts, 01199

  • CoxHealth South Hospital

    Springfield, Missouri, 65807

  • 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) in the Treatment of Persistent or Recurrent Carcinoma of the Cervix (BMS Study CA182-048)

This phase II trial studies how well brivanib alaninate works in treating patients with cervical cancer that has come back. Brivanib alaninate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth or by blocking blood flow to the tumor.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To estimate the proportion of patients with persistent or recurrent cervical cancer, who survive progression-free for at least 6 months and the proportion of patients who have objective tumor response (complete or partial), treated with brivanib (brivanib alaninate).

II. To determine the nature and degree of toxicity of brivanib in this cohort of patients.

SECONDARY OBJECTIVES:

  1. To estimate the progression-free survival (PFS) and overall survival (OS) of patients with persistent or recurrent cervical cancer treated with brivanib.

TERTIARY OBJECTIVES:

  1. To obtain the serum expression levels of surrogate markers of brivanib effects including angiogenic factors (vascular endothelial growth factor [VEGF] and basic fibroblast growth factor [bFGF]) and markers of endothelial damage (E-selectin, vascular cell adhesion molecule 1 [VCAM-1], and (intercellular adhesion molecule 1 [ICAM-1]). (exploratory) II. To determine whether these marker expression levels alone or in combination are associated with response, PFS, or overall survival. (exploratory)

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 therapy, 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
Medical subject headings
Uterine Cervical Neoplasms

What participants receive

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

  • Brivanib AlaninateDrug

    Also called BMS 582664, BMS-582664

    Given PO

  • Laboratory Biomarker AnalysisOther

    Correlative studies

Study groups in NCT01267253
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. Objective Tumor Response

    Proportion of participants with objective tumor response. Objective tumor response is defined as complete or partial tumor response assessed by RECIST 1.1

    Measured: Every other cycle for first 6 months; then every 3 months thereafter until disease progression confirmed; and at any other time if clinically indicated based on symptoms or physical signs suggestive of progressive disease.

  2. PFS for at Least 6 Months Without Non-protocol Therapy From Study Entry.

    Proportion of participants who survive progression-free for at least 6 months without non-protocol therapy from study entry. Progression is assessed by RECIST 1.1.

    Measured: Every other cycle for first 6 months; then every 3 months therafter until disease progression confirmed; and at any other time if cliniclly indicated based on symptoms or physical signs suggestive of progressive disease

  3. Adverse Events (Grade 3 or Higher) During Treatment Period

    Number of participants with a maximum grade of 3 or higher during treatment period. Adverse events are graded and categorized using CTCAE v.4.0

    Measured: During treatment period and up to 30 days after stopping the study treatment.

Secondary outcomes (2)

  1. Progression-free Survival

    Progression-free survival is the period of time from study entry to time of disease progression, death or date of last contact, whichever occurs first. Progression is assessed by RECIST 1.1

    Measured: From study entry to time of progression or death, whichever occurs first, up to 5 years of follow-up

  2. Overall Survival

    Overall survival is defined as the duration of time from study entry to time of death or the date of last contact..

    Measured: From study entry to time of death or the date of last contact, up to 5 years of follow-up.

Timeline

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

  1. First posted28 Dec 2010 (estimated)
  2. Study start4 Apr 2011
  3. Primary completion28 Feb 2014
  4. Study completion28 Feb 2014

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
31 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01267253
Sponsor's protocol ID
GOG-0227G
Other IDs
NCI-2011-03814, CDR0000690083, CA182-048, GOG-0227G, GOG-0227G, GOG-0227G, U10CA180868, U10CA027469
Status last verified
Mar 2019
First submitted
24 Dec 2010
Last updated
20 Mar 2019
Data monitoring committee
Yes

Publications

  • Chan JK, Deng W, Higgins RV, Tewari KS, Bonebrake AJ, Hicks M, Gaillard S, Ramirez PT, Chafe W, Monk BJ, Aghajanian C. A phase II evaluation of brivanib in the treatment of persistent or recurrent carcinoma of the cervix: An NRG Oncology/Gynecologic Oncology Group study. Gynecol Oncol. 2017 Sep;146(3):554-559. doi: 10.1016/j.ygyno.2017.05.033. Epub 2017 Jul 18.

    PubMed 28728751

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Brivanib Alaninate and Laboratory Biomarker Analysis in people with Cervical Adenocarcinoma and Cervical Adenosquamous Carcinoma, run by Gynecologic Oncology Group at 43 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 35 inclusion and 30 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 20 Mar 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 43 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 4 Jan 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?

Objective Tumor Response (time frame: Every other cycle for first 6 months; then every 3 months thereafter until disease progression confirmed; and at any other time if clinically indicated based on symptoms or physical signs suggestive of progressive disease.). The study lists 3 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 NCT01267253, which also lists 1 linked publication.

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 20 Mar 2019.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Keep searching with a free account

You’ve used your 3 free searches for this session. Log in or create a free AzTrials account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in