Phase II Evaluation of BIBF 1120 in the Treatment of Bevacizumab-Resistant, Persistent, or Recurrent Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Carcinoma
- Recurrent or persistent epithelial ovarian, fallopian tube, or primary peritoneal
carcinoma w/ histologic documentation of the original primary tumor via the pathology
- serious, endometrioid, mucinous, or clear cell adenocarcinoma
- undifferentiated, mixed epithelial or transitional cell carcinoma
- Brenner's Tumor
- adenocarcinoma NOS
- Had treatment-free interval following response to bevacizumab (CR, PR, or SD) of < 6
months, or have progressed during treatment w/ a bevacizumab-containing therapy
- Measurable disease as defined by RECIST 1.1. 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
- Have at least one "target lesion" to assess response as defined by RECIST 1.1. Tumors
in a previously irradiated field will be designated as "non-target" lesions
- Must have a GOG Performance Status of 0 or 1
- Free of active infection requiring antibiotics. Exception: uncomplicated UTI
- Recovery from effects of recent surgery, radiotherapy, or chemotherapy
- Hormonal therapy directed at the malignant tumor must be d/c at least a week
prior to registration. Hormone replacement therapy is permitted
- Other prior therapy directed at malignant tumor, including immunologic agents,
must be d/c at least 3 weeks prior to registration; 4 weeks if prior therapy was
- Prior therapy
- Patients must have had one prior platinum-based chemotherapeutic regimen for
management of primary disease containing carboplatin, cisplatin, or another
organoplatinum compound. This initial treatment may have included
intraperitoneal therapy, high-dose therapy, consolidation, non-cytotoxic agents
or extended therapy administered after surgical or non-surgical assessment.
- Allowed, to receive, but are not required to receive, 1 additional cytotoxic
regimen for management of recurrent or persistent disease according to the
- Patients who have received only one prior cytotoxic regimen (platinum-based
regimen for management of primary disease), must have a platinum-free
interval of less than 12 months, or have progressed during platinum-based
therapy, or have persistent disease after a platinum-based therapy.
- Patients must NOT have received any non-cytotoxic therapy for management of
recurrent or persistent disease other than bevacizumab. Patients are
allowed to receive, but are not required to receive, biologic
(non-cytotoxic) therapy as part of their primary treatment regimen.
- Must have adequate:
- Bone marrow function: Absolute neutrophil count (ANC) ≥ 1,500/mcl, equivalent to
(CTCAE v4.0) grade 1. Platelets ≥ 100,000/mcl. Hemoglobin (Hb) ≥ 9.0 g/dL
- Renal function: creatinine ≤ 1.5 x upper limit of normal (ULN)
- Hepatic function: Bilirubin should be w/in normal limits (CTCAE v4.0, grade 1).
ALT/AST, should be ≤ 1.5 x ULN (CTCAE v4.0, grade 1). For patients w/ liver
metastases, ALT/AST should be ≤ 2.5 x ULN; Alkaline phosphatase should be ≤ 2.5
x ULN (CTCAE v4.0, grade 1)
- Neurologic function: Neuropathy ≤ CTCAE v4.0, grade 1
- Blood coagulation parameters: PT w/ international normalized ratio (INR) < 1.5 x ULN
& a PTT < 1.5 x ULN (or an in-range PTT if on a stable dose of therapeutic heparin).
Low molecular weight heparin (enoxaparin or alternative anticoagulants (other than
warfarin)) are acceptable.
- Signed informed consent & authorization permitting release of personal health
- Negative serum pregnancy test if of childbearing potential prior to study entry & use
of effective form of contraception until 3 months after receiving last drug treatment
- Patients may have undergone a major or minor surgical procedure as long as:
- > 28 days prior to the first date of study therapy
- Core biopsy or IV Port placement greater than 7 days prior to the first date of
- Previous treatment w/ BIBF 1120.
- Pregnant or breastfeeding.
- Received radiation to more than 25% of marrow-bearing areas
- History of other invasive malignancies, w/ the exception of non-melanoma skin cancer,
if there is any evidence of other malignancy being present w/in the last five years.
- Received prior radiotherapy to any portion of the abdominal cavity or pelvis OTHER
THAN for treatment of ovarian, fallopian tube, or primary peritoneal cancer w/in the
last 5 years.
- Prior chemotherapy for any abdominal or pelvic tumor OTHER THAN for the treatment of
ovarian, fallopian tube, or primary peritoneal cancer or localized breast cancer w/in
the last 5 years.
- A history of abdominal or tracheal-esophageal fistula, or gastrointestinal
- A history of intra-abdominal abcess w/in 6 months of enrollment
- Serious, uncontrolled, concomitant disorder(s) such as diabetes mellitus
- Patients w/ clinically significant cardiovascular disease including: uncontrolled
hypertension: systolic > 150 mm Hg/diastolic > 90 mm Hg; unstable angina or who have
had a myocardial infarction w/in the past six months prior to registration;
congestive heart failure; cardiac arrhythmia requiring medication (doesn't include
asymptomatic atrial fibrillation); grade 2 or greater peripheral vascular disease (at
least brief (<24 hours) episodes of ischemia managed non-surgically & w/o permanent
- Serious non-healing wound, ulcer, or bone factor.
o Granulating incisions healing by secondary intention w/ no evidence of fascial
dehiscence or infection ARE eligible but require weekly wound examinations.
- Active bleeding or pathologic conditions that carry high risk of bleeding, such as
known bleeding disorder, coagulopathy, or tumor involving major vessels.
- History/evidence upon physical examination of CNS disease, including primary brain
tumor, seizures not controlled w/ standard medical therapy, any brain metastases,
CVA, TIA, or subarachnoid hemorrhage w/in 6 months of the first date of treatment on
- Central pulmonary metastases/recent hemoptysis (≥1/2 tsp of red blood) w/in 28 days
- Clinically significant proteinuria (i.e. >Grade 1) or UPC ratio above 1.0
- Suspicion of transmural tumor bowel involvement based on the investigator's
- Clinical symptoms/signs of gastrointestinal obstruction & require IV hydration &/or
- Patients taking warfarin are not eligible