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Phase II Evaluation of BIBF 1120 in the Treatment of Bevacizumab-Resistant, Persistent, or Recurrent Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Carcinoma

Phase 2
18 Years
Open (Enrolling)
Ovarian Cancer, Fallopian Tube Cancer, Peritoneal Cancer

Thank you

Trial Information

Phase II Evaluation of BIBF 1120 in the Treatment of Bevacizumab-Resistant, Persistent, or Recurrent Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Carcinoma

Ovarian cancer patients with platinum-resistant and refractory disease have the lowest
response rates to relapse chemotherapy: various chemotherapeutic agents, such as paclitaxel,
liposomal doxorubicin, topotecan, docetaxel, platinum, etoposide, ifosfamide, gemcitabine,
and vinorelbine are available but result in response rates of 7-40%. Unfortunately, relapse
therapy is not curative and treatment is only palliative. Recently two phase II trials
demonstrated that anti-angiogenic therapy with bevacizumab alone or in combination with
chemotherapy in women with recurrent disease had response rates ranging from 16-24% with an
acceptable toxicity profile. However, resistance can develop to VEGF inhibition. Therefore
other novel anti-angiogenic agents, such as BIBF 1120, should be evaluated in the treatment
of ovarian cancer.

Inclusion Criteria:

- 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
w/ bevacizumab

- 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
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

- 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
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

- Clinical symptoms/signs of gastrointestinal obstruction & require IV hydration &/or

- Patients taking warfarin are not eligible

Type of Study:


Study Design:

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Progression Free Survival

Outcome Description:

To assess the activity of BIBF 1120 as measured by the proportion of patients who survive progression-free for at least 6 months after initiating study therapy in patients with bevacizumab-resistant, persistent or recurrent epithelial ovarian, fallopian tube, or primary peritoneal carcinoma.

Outcome Time Frame:

6 months

Safety Issue:


Principal Investigator

Angeles A Secord, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Duke University


United States: Food and Drug Administration

Study ID:




Start Date:

February 2013

Completion Date:

September 2014

Related Keywords:

  • Ovarian Cancer
  • Fallopian Tube Cancer
  • Peritoneal Cancer
  • Recurrent epithelial ovarian carcinoma
  • Persistent epithelial ovarian carcinoma
  • Bevacizumab resistant epithelial ovarian carcinoma
  • Ovarian Neoplasms
  • Peritoneal Neoplasms
  • Fallopian Tube Neoplasms



Duke Cancer Institute Durham, North Carolina  27710