Brivanib Alaninate in Treating Patients With Persistent or Recurrent Cervical Cancer

NCT ID: NCT01267253

Last Updated: 2019-03-20

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 31 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-04-04
• Study Completion Date: 2014-02-28

Brief 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.

Detailed Description

PRIMARY OBJECTIVES:

I. 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:

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

TERTIARY OBJECTIVES:

I. 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.

Conditions

Cervical Adenocarcinoma; Cervical Adenosquamous Carcinoma; Cervical Squamous Cell Carcinoma, Not Otherwise Specified; Persistent Disease; Recurrent Cervical Carcinoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Treatment (brivanib alaninate)

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

Group Type: EXPERIMENTAL

Brivanib Alaninate

Intervention Type: DRUG

Given PO

Laboratory Biomarker Analysis

Intervention Type: OTHER

Correlative studies

Interventions

Brivanib Alaninate

Given PO

Intervention Type: DRUG

Laboratory Biomarker Analysis

Correlative studies

Intervention Type: OTHER

Other Intervention Names

BMS 582664; BMS-582664

Eligibility Criteria

Inclusion Criteria

• 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
• 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

Exclusion Criteria

• 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
• 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Gynecologic Oncology Group

NETWORK

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

John K Chan

Role: PRINCIPAL_INVESTIGATOR

NRG Oncology

Locations

Saint Joseph's Hospital and Medical Center

Phoenix, Arizona, United States

Providence Saint Joseph Medical Center/Disney Family Cancer Center

Burbank, California, United States

UCSF Medical Center-Mount Zion

San Francisco, California, United States

Smilow Cancer Hospital Care Center at Saint Francis

Hartford, Connecticut, United States

The Hospital of Central Connecticut

New Britain, Connecticut, United States

Beebe Medical Center

Lewes, Delaware, United States

Christiana Care Health System-Christiana Hospital

Newark, Delaware, United States

Florida Hospital Orlando

Orlando, Florida, United States

Sarasota Memorial Hospital

Sarasota, Florida, United States

Memorial Health University Medical Center

Savannah, Georgia, United States

Rush University Medical Center

Chicago, Illinois, United States

University of Chicago Comprehensive Cancer Center

Chicago, Illinois, United States

Sudarshan K Sharma MD Limited-Gynecologic Oncology

Hinsdale, Illinois, United States

Saint Vincent Hospital and Health Care Center

Indianapolis, Indiana, United States

Greater Baltimore Medical Center

Baltimore, Maryland, United States

Union Hospital of Cecil County

Elkton, Maryland, United States

Baystate Medical Center

Springfield, Massachusetts, United States

Michigan Cancer Research Consortium NCORP

Ann Arbor, Michigan, United States

Saint Joseph Mercy Hospital

Ann Arbor, Michigan, United States

Saint Mary Mercy Hospital

Livonia, Michigan, United States

Saint Joseph Mercy Oakland

Pontiac, Michigan, United States

Lake Huron Medical Center

Port Huron, Michigan, United States

University of Mississippi Medical Center

Jackson, Mississippi, United States

CoxHealth South Hospital

Springfield, Missouri, United States

Nebraska Methodist Hospital

Omaha, Nebraska, United States

Women's Cancer Center of Nevada

Las Vegas, Nevada, United States

Cooper Hospital University Medical Center

Camden, New Jersey, United States

Carolinas Medical Center/Levine Cancer Institute

Charlotte, North Carolina, United States

Summa Akron City Hospital/Cooper Cancer Center

Akron, Ohio, United States

Case Western Reserve University

Cleveland, Ohio, United States

Riverside Methodist Hospital

Columbus, Ohio, United States

Kettering Medical Center

Kettering, Ohio, United States

UH Seidman Cancer Center at Lake Health Mentor Campus

Mentor, Ohio, United States

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, United States

Oklahoma Cancer Specialists and Research Institute-Tulsa

Tulsa, Oklahoma, United States

Abington Memorial Hospital

Abington, Pennsylvania, United States

West Penn Hospital

Pittsburgh, Pennsylvania, United States

Women and Infants Hospital

Providence, Rhode Island, United States

Baylor All Saints Medical Center at Fort Worth

Fort Worth, Texas, United States

Lyndon Baines Johnson General Hospital

Houston, Texas, United States

M D Anderson Cancer Center

Houston, Texas, United States

Virginia Commonwealth University/Massey Cancer Center

Richmond, Virginia, United States

University of Wisconsin Hospital and Clinics

Madison, Wisconsin, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 28728751 (View on PubMed)

Other Identifiers

NCI-2011-03814

Identifier Type: REGISTRY

Identifier Source: secondary_id

CDR0000690083

Identifier Type: -

Identifier Source: secondary_id

CA182-048

Identifier Type: -

Identifier Source: secondary_id

GOG-0227G

Identifier Type: -

Identifier Source: secondary_id

GOG-0227G

Identifier Type: OTHER

Identifier Source: secondary_id

GOG-0227G

Identifier Type: OTHER

Identifier Source: secondary_id

U10CA180868

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U10CA027469

Identifier Type: NIH

Identifier Source: secondary_id

View Link

GOG-0227G

Identifier Type: -

Identifier Source: org_study_id