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About
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.
Full description
PRIMARY OBJECTIVES:
I. 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:
I. 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:
I. 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.
Enrollment
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Volunteers
Inclusion criteria
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
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
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:
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
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 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
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:
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
Primary purpose
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45 participants in 1 patient group
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Data sourced from clinicaltrials.gov
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