Overview

BIBF 1120 in Bevacizumab Resistant, Persistent, or Recurrent Epithelial Ovarian Cancer

Status:
Completed
Trial end date:
2018-02-01
Target enrollment:
0
Participant gender:
Female
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.
Phase:
Phase 2
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
AA Secord
Collaborator:
Boehringer Ingelheim
Treatments:
Bevacizumab
Nintedanib
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