Know Cancer

forgot password

A Phase II Evaluation of Brivanib (BMS582664, IND #108417) in the Treatment of Persistent or Recurrent Carcinoma of the Cervix (BMS Study CA182-048)

Phase 2
18 Years
Not Enrolling
Cervical Cancer

Thank you

Trial Information

A Phase II Evaluation of Brivanib (BMS582664, IND #108417) in the Treatment of Persistent or Recurrent Carcinoma of the Cervix (BMS Study CA182-048)



- To assess the activity of brivanib for patients with persistent or recurrent carcinoma
of the cervix with the frequency of patients who survive progression free for at least
6 months after initiating therapy or have objective tumor response.

- To determine the nature and degree of toxicity of brivanib as assessed by the NCI
Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 in this cohort of


- To characterize the distribution of progression-free survival (PFS) and overall

- To determine the effect of brivanib on the duration of objective response in persistent
or recurrent carcinoma of the cervix.


- To obtain the serum expression levels of surrogate markers of brivanib effects
including angiogenic factors (VEGF and bFGF) and markers of endothelial damage
(E-selectin, VCAM-1, and ICAM-1). (exploratory)

- To determine whether these marker expression levels alone or in combination are
associated with response, PFS, or overall survival. (exploratory)

OUTLINE: This is a multicenter study.

Patients receive oral brivanib once daily on days 1-28. Courses repeat every 28 days in the
absence of disease progression or unacceptable toxicity.

Serum samples may be collected periodically for correlative biomarker studies.

After completion of study therapy, patients are followed up every 3 months.

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 RECIST 1.1 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 CT, 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 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 must have had one prior systemic chemotherapeutic regimen for management of
advanced, metastatic, or recurrent carcinoma of the cervix

- Chemotherapy administered in conjunction with primary radiation as a
radio-sensitizer is not counted as a systemic chemotherapy regimen

- 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 according to
the following definition:

- Due to the novel nature of biologic compounds, patients are encouraged to
enroll on second-line non-cytotoxic studies prior to receiving additional
cytotoxic therapy

- 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

- No known brain metastases


- 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

- Absolute neutrophil count (ANC) greater than or equal to 1,500/mcl

- Platelets greater than or equal to100,000/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

- AST and ALT less than or equal to 3 x ULN

- Bilirubin less than or equal to 1.5 x ULN

- Alkaline phosphatase less than or equal to 2.5 x ULN

- Albumin greater than or equal to 2.5 g/dL

- PT such that international normalized ratio (INR) is < 1.5 x ULN

- No baseline serum potassium < 3.5 mmol/L (potassium supplementation may be given to
restore the serum potassium above this level prior to entry study)

- Neuropathy (sensory and motor) less than or equal to grade 1

- Patients should be free of active infection requiring antibiotics (with the exception
of uncomplicated UTI)

- Not pregnant or nursing

- Patients of childbearing potential must have a negative serum pregnancy test
performed 48 hours prior to study entry

- Patients must 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 ECG should be repeated if QTc is found to be > 450 msec

- QTc must NOT be > 450 msec on both ECGs performed during the same visit

- 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

- No gastrointestinal bleeding or any other hemorrhage/bleeding event > grade 3 of the
NCI CTCAE within 30 days prior to study entry

- No poor wound healing, non-healing ulcers, or bone fractures within the last 3 months

- No uncontrolled or significant cardiovascular disease including any of the following:

- Myocardial infarction within 12 months

- Uncontrolled angina within 12 months

- New York Heart Association (NYHA) class III-IV congestive heart failure

- Uncontrolled hypertension despite anti-hypertensive therapy

- BP must be less than or equal to 140/90 at screening

- Patients with a history of hypertension who are receiving treatment with
calcium channel blockers that are CYP3A4 inhibitors should be changed to an
alternative antihypertensive medication before study entry

- History of stroke, TIA, or other CNS ischemic event

- Cardiac arrhythmias requiring anti-arrhythmic therapy other than beta blockers
or digoxin

- Patients must have pre-therapy LVEF testing and have an ejection fraction >
institutional LLN

- Patients with valvular heart disease > grade 2

- No serious uncontrolled medical disorder or active infection that would impair the
ability of the subject to receive protocol therapy or whose control may be
jeopardized by the complications of this therapy

- No pre-existing thyroid abnormality with thyroid function that cannot be maintained
in the normal range with medication

- No hyponatremia (sodium < 130 mEq/L)

- No active/known HIV, hepatitis B, or hepatitis C

- No inability to swallow tablets or untreated malabsorption syndrome


- See Disease Characteristics

- Recovered from effects of recent surgery, radiotherapy, or chemotherapy

- At least 4 weeks must have elapsed from the time of any major surgical procedure

- 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

- Patients on therapeutic warfarin anticoagulation are excluded

- Anticoagulation with low molecular weight heparin is allowed provided the
patient's PT is such that international normalized ratio (INR) is < 1.5 x ULN

- No prior therapy with brivanib, anti-vascular, anti-PDGFR (platelet-derived growth
factor receptor), or anti-FGFR (fibroblast growth factor receptor) therapy

- Patients are 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

- No patients that are on required chronic anti-platelet therapy (aspirin > 300 mg/day,
or clopidogrel greater than or equal to 75 mg/day)

- Patients may NOT receive amifostine or other protective reagents

Type of Study:


Study Design:

Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Progression-free for at least 6 months

Safety Issue:


Principal Investigator

John K. Chan, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

University of California, San Francisco


United States: Federal Government

Study ID:




Start Date:

April 2011

Completion Date:

Related Keywords:

  • Cervical Cancer
  • cervical adenocarcinoma
  • cervical adenosquamous cell carcinoma
  • cervical small cell carcinoma
  • cervical squamous cell carcinoma
  • recurrent cervical cancer
  • stage IVA cervical cancer
  • stage IVB cervical cancer
  • Uterine Cervical Neoplasms



University of Chicago Cancer Research Center Chicago, Illinois  60637
CCOP - Christiana Care Health Services Wilmington, Delaware  19899
George Bray Cancer Center at the Hospital of Central Connecticut - New Britain Campus New Britain, Connecticut  06050
Baystate Regional Cancer Program at D'Amour Center for Cancer Care Springfield, Massachusetts  01199
CCOP - Michigan Cancer Research Consortium Ann Arbor, Michigan  48106
Saint Joseph Mercy Cancer Center Ann Arbor, Michigan  48106-0995
Case Comprehensive Cancer Center Cleveland, Ohio  44106-5065
University of Wisconsin Paul P. Carbone Comprehensive Cancer Center Madison, Wisconsin  53792-6164
St. Joseph's Hospital and Medical Center Phoenix, Arizona  85001-2071
Rush University Medical Center Chicago, Illinois  60612-3824
Sarasota Memorial Hospital Sarasota, Florida  34239
Blumenthal Cancer Center at Carolinas Medical Center Charlotte, North Carolina  28232-2861
Hulston Cancer Center at Cox Medical Center South Springfield, Missouri  65807
Lake/University Ireland Cancer Center Mentor, Ohio  44060
Women and Infants Hospital of Rhode Island Providence, Rhode Island  02905
Florida Hospital Cancer Institute at Florida Hospital Orlando Orlando, Florida  32803-1273
Stony Brook University Cancer Center Stony Brook, New York  11794-8174
Riverside Methodist Hospital Cancer Care Columbus, Ohio  43214
UCSF Helen Diller Family Comprehensive Cancer Center San Francisco, California  94115
Curtis and Elizabeth Anderson Cancer Institute at Memorial Health University Medical Center Savannah, Georgia  31403-3089
University of Mississippi Cancer Clinic Jackson, Mississippi  39216-4505
Oklahoma University Cancer Institute Oklahoma City, Oklahoma  73104
M. D. Anderson Cancer Center at University of Texas Houston, Texas  77030-4009
Virginia Commonwealth University Massey Cancer Center Richmond, Virginia  23298-0037
Methodist Estabrook Cancer Center Omaha, Nebraska  68114-4199
Saint Francis/Mount Sinai Regional Cancer Center at Saint Francis Hospital and Medical Center Hartford, Connecticut  06105
Cancer Care Associates - Saint Francis Campus Tulsa, Oklahoma  74136-1929
Rosenfeld Cancer Center at Abington Memorial Hospital Abington, Pennsylvania  19001
Cancer Institute of New Jersey at Cooper - Voorhees Voorhees, New Jersey  08043
Charles F. Kettering Memorial Hospital Kettering, Ohio  45429
Western Pennsylvania Cancer Institute at Western Pennsylvania Hospital Pittsburgh, Pennsylvania  15224-1791
Tunnell Cancer Center at Beebe Medical Center Lewes, Delaware  19958
Greater Baltimore Medical Center Cancer Center Baltimore, Maryland  21204
St. Mary Mercy Hospital Livonia, Michigan  48154
St. Joseph Mercy Oakland Pontiac, Michigan  48341-2985
Mercy Regional Cancer Center at Mercy Hospital Port Huron, Michigan  48060
Summa Center for Cancer Care at Akron City Hospital Akron, Ohio  44309-2090
Union Hospital of Cecil County Elkton MD, Maryland  21921
Gynecologic Oncology Hinsdale, Illinois  60521
Women's Cancer Center - La Canada Las Vegas, Nevada  89169
Roy and Patricia Disney Family Cancer Center at Providence Saint Joseph Medical Center Burbank, California  91505
Lyndon B. Johnson General Hospital Houston, Texas  77026-1967
St. Vincent Oncology Center Indianapolis, Indiana  46260
All Saints Episcopal Hospital - Fort Worth Fort Worth, Texas  76104