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

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2014 by Duke University
Sponsor:
Collaborator:
Boehringer Ingelheim
Information provided by (Responsible Party):
AA Secord, Duke University Medical Center
ClinicalTrials.gov Identifier:
NCT01669798
First received: July 10, 2012
Last updated: October 17, 2014
Last verified: October 2014
  Purpose

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.


Condition Intervention Phase
Ovarian Cancer
Fallopian Tube Cancer
Peritoneal Cancer
Drug: BIBF 1120
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Evaluation of BIBF 1120 in the Treatment of Bevacizumab-Resistant, Persistent, or Recurrent Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Carcinoma

Resource links provided by NLM:


Further study details as provided by Duke University:

Primary Outcome Measures:
  • Progression Free Survival [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Objective Tumor Response via RECIST 1.1 [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    To determine the proportion of patients who have objective tumor response (complete or partial) based on RECIST 1.1 criteria.

  • Duration of Progression-Free Survival [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    To characterize the duration of progression-free survival and overall survival; Progression-Free Survival (PFS) is defined as the duration of time from study entry to time of progression or death, whichever occurs first.

  • Objective Tumor Response Based on GCIG CA-125 Criteria [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    To determine the proportion of patients who have objective tumor response (complete or partial) based on Gynaecologic Cancer InterGroup(GCIG) CA-125 criteria.

  • VEGF Levels Correlated With Treatment Outcome [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    To measure baseline levels of VEGF and correlate with treatment outcome

  • Additional Growth Factor Correlation with Treatment Response [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    To measure baseline and on treatment levels of additional growth factors that may be co- or counter- regulated with VEGF and correlate with response to treatment

  • Coagulation and Endothelial Cell Activation Markers [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    To measure baseline and on treatment levels of coagulation and endothelial cell activation markers that may predict thrombotic or bleeding risks related to treatment

  • Adverse Event Frequency and Severity [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
    To determine frequency and severity of adverse events as assessed using NCI Common Toxicity Criteria version 4.


Estimated Enrollment: 56
Study Start Date: February 2013
Estimated Study Completion Date: September 2015
Estimated Primary Completion Date: June 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: BIBF 1120
BIBF 1120 will be administered at a daily oral dose of 200 mg BID until disease progression or adverse effects prohibit further therapy.
Drug: BIBF 1120
PO 200mg BID
Other Names:
  • Vargatef™
  • Nintedanib

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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 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

    • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01669798

Contacts
Contact: Beatrice Z Nelson, RN, BSN, OCN 919-684-3792 beatrice.nelson@duke.edu

Locations
United States, North Carolina
Duke Cancer Institute Recruiting
Durham, North Carolina, United States, 27710
Contact: Beatrice Z Nelson, RN, BSN, OCN    919-684-3792    beatrice.nelson@dm.duke.edu   
Principal Investigator: Angeles A Secord, MD         
Sub-Investigator: Andrew Berchuck, MD         
Sub-Investigator: Laura J Havrilesky, MD         
Sub-Investigator: Fidel A Valea, MD         
Sub-Investigator: Paula S Lee, MD         
Sub-Investigator: Stephanie Gaillard, MD, PhD         
United States, Virginia
University of Virginia Recruiting
Charlottesville, Virginia, United States, 22908
Contact: Sanja Arapovic    434-924-2745    su2x@virginia.edu   
Principal Investigator: Linda Duska, MD         
Sub-Investigator: Susan Modesitt, MD         
Sub-Investigator: Leigh Cantrell, MD         
Virginia Oncology Associates Recruiting
Norfolk, Virginia, United States, 23502
Contact: Wendi Gobhardt, RN, BSN, OCN    757-213-5813    wendi.gobhardt@usoncology.com   
Principal Investigator: Michael E McCollum, MD         
Sub-Investigator: Robert C Squatrito, MD         
Sub-Investigator: Stacey Rogers, MD         
Sub-Investigator: Cori O Damuth, NP-C         
Sub-Investigator: Shanti Powers, PA-C         
Sponsors and Collaborators
AA Secord
Boehringer Ingelheim
Investigators
Principal Investigator: Angeles A Secord, MD Duke University
  More Information

No publications provided

Responsible Party: AA Secord, Associate Professor, Duke University Medical Center
ClinicalTrials.gov Identifier: NCT01669798     History of Changes
Other Study ID Numbers: Pro00033060
Study First Received: July 10, 2012
Last Updated: October 17, 2014
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board
United States: Data and Safety Monitoring Board

Keywords provided by Duke University:
Recurrent epithelial ovarian carcinoma
Persistent epithelial ovarian carcinoma
Bevacizumab resistant epithelial ovarian carcinoma

Additional relevant MeSH terms:
Fallopian Tube Neoplasms
Ovarian Neoplasms
Adnexal Diseases
Endocrine Gland Neoplasms
Endocrine System Diseases
Fallopian Tube Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Gonadal Disorders
Neoplasms
Neoplasms by Site
Ovarian Diseases
Urogenital Neoplasms
Bevacizumab
Nintedanib
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Antineoplastic Agents
Enzyme Inhibitors
Growth Inhibitors
Growth Substances
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on October 30, 2014