Brivanib in Treating Patients With Persistent or Recurrent Cervical Cancer

This study has suspended participant recruitment.
Sponsor:
Collaborator:
Information provided by:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT01267253
First received: December 24, 2010
Last updated: September 6, 2012
Last verified: September 2012
  Purpose

RATIONALE: Brivanib 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.

PURPOSE: This phase II trial is studying how well brivanib works in treating patients with persistent or recurrent cervical cancer.


Condition Intervention Phase
Cervical Cancer
Drug: brivanib alaninate
Other: laboratory biomarker analysis
Phase 2

Study Type: Interventional
Study Design: Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Evaluation of Brivanib (BMS582664, IND #108417) in the Treatment of Persistent or Recurrent Carcinoma of the Cervix (BMS Study CA182-048)

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Progression-free for at least 6 months [ Designated as safety issue: No ]
  • Objective tumor response (complete or partial) [ Designated as safety issue: No ]
  • Adverse events as assessed by NCI CTCAE v4.0 [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Progression-free survival [ Designated as safety issue: No ]
  • Overall survival [ Designated as safety issue: No ]

Estimated Enrollment: 51
Study Start Date: April 2011
Estimated Primary Completion Date: February 2013 (Final data collection date for primary outcome measure)
Detailed Description:

OBJECTIVES:

Primary

  • 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 patients.

Secondary

  • To characterize the distribution of progression-free survival (PFS) and overall survival.
  • To determine the effect of brivanib on the duration of objective response in persistent or recurrent carcinoma of the cervix.

Tertiary

  • 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • 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

PATIENT CHARACTERISTICS:

  • 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

PRIOR CONCURRENT THERAPY:

  • 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 disease
  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01267253

  Show 44 Study Locations
Sponsors and Collaborators
Gynecologic Oncology Group
Investigators
Principal Investigator: John K. Chan, MD University of California, San Francisco
  More Information

Additional Information:
No publications provided

Responsible Party: Philip J. DiSaia, Gynecologic Oncology Group
ClinicalTrials.gov Identifier: NCT01267253     History of Changes
Other Study ID Numbers: CDR0000690083, GOG-0227G
Study First Received: December 24, 2010
Last Updated: September 6, 2012
Health Authority: United States: Federal Government

Keywords provided by National Cancer Institute (NCI):
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

Additional relevant MeSH terms:
Uterine Cervical Neoplasms
Uterine Neoplasms
Genital Neoplasms, Female
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Uterine Cervical Diseases
Uterine Diseases
Genital Diseases, Female

ClinicalTrials.gov processed this record on August 20, 2014