BIBF 1120 in Bevacizumab Resistant, Persistent, or Recurrent Epithelial Ovarian Cancer
Condition: Ovarian Cancer; Fallopian Tube Cancer; Peritoneal Cancer
MeSH terms: Ovarian Neoplasms; Carcinoma, Ovarian Epithelial; Fallopian Tube Neoplasms
Intervention: BIBF 1120
Intervention description: PO 200mg BID
Intervention MeSH terms: Nintedanib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 32.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Recurrent epithelial ovarian carcinoma; Persistent epithelial ovarian carcinoma; Bevacizumab resistant epithelial ovarian carcinoma

Summary:

      The main purpose of this study is to see if BIBF 1120 can increase the number of women with
      bevacizumab resistant, persistent, or recurrent epithelial ovarian cancer who do not progress
      for at least six months.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Recurrent or persistent epithelial ovarian, fallopian tube, or primary peritoneal
             carcinoma w/ histologic documentation of the original primary tumor via the pathology
             report:

               -  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 or detectable disease. Measurable is 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. Detectable defined as no measurable disease but either
             ascities/pleural effusion or solid/cystic abnormalities that don't meet RECIST 1.1 -
             both within the setting of CA125 >2xULN

          -  Those with measurable disease must 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 ECOG 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
                  w/ bevacizumab

          -  Prior therapy

               -  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 not required to receive, 2 additional cytotoxic regimens
                  for management of recurrent or persistent disease according to the following:

                    -  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
             information

          -  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
                  study therapy

        Exclusion Criteria:

          -  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 perforation

          -  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 deficit.

          -  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 this
             study.

          -  Central pulmonary metastases/recent hemoptysis (≥1/2 tsp of red blood) w/in 28 days of
             registration.

               -  Clinically significant proteinuria (i.e. >Grade 1) or UPC ratio above 1.0

               -  Suspicion of transmural tumor bowel involvement based on the investigator's
                  discretion.

          -  Clinical symptoms/signs of gastrointestinal obstruction & require IV hydration &/or
             nutrition.

          -  Patients taking warfarin are not eligible