Doxorubicin + BIBF 1120 in Patients for Ovarian Cancer

This study has been terminated.
(Drug Availability Issue caused funding to be withdrawn; enrolled patients will remain on study receiving study drug and follow-up per protocol)
Sponsor:
Collaborator:
Boehringer Ingelheim
Information provided by (Responsible Party):
Hoosier Cancer Research Network
ClinicalTrials.gov Identifier:
NCT01485874
First received: December 2, 2011
Last updated: August 20, 2014
Last verified: August 2014
  Purpose

The purpose of this trial is to determine whether BIBF 1120 can be safely combined with pegylated liposomal doxorubicin (phase I), and to determine the clinical activity of the combination in patients with platinum-resistant ovarian cancer (phase II).


Condition Intervention Phase
Ovarian Cancer
Drug: Doxil (Pegylated Liposomal Doxorubicin)
Drug: BIBF 1120
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I-II Clinical Trial of Pegylated Liposomal Doxorubicin (Doxil®) in Combination With BIBF 1120 in Patients With Ovarian Cancer: Hoosier Oncology Group GYN10-149

Resource links provided by NLM:


Further study details as provided by Hoosier Cancer Research Network:

Primary Outcome Measures:
  • Phase I: Safety and Toxicity of Treatment Regimen [ Time Frame: 3 months ] [ Designated as safety issue: Yes ]
    To find the maximum tolerated dose (MTD) to be used during the Phase II trial and evaluate the safety and toxicity of the combination BIBF 1120 plus PLD in patients with recurrent or resistant epithelial ovarian or endometrial cancer.

  • Phase II: Objective Response Rate [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    To assess response rate (objective response) in patients with recurrent or resistant epithelial ovarian cancer treated with BIBF 1120 plus PLD.


Secondary Outcome Measures:
  • Phase I and II: Progression-Free Survival [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    To determine the progression-free survival of Phase I and II patients with recurrent or resistant epithelial ovarian cancer treated with BIBF 1120 plus PLD.

  • Phase I and II: Clinical Benefit [ Time Frame: 12 months ] [ Designated as safety issue: No ]

    To determine the rate of clinical benefit for Phase I and II defined as:

    • the number of patients experiencing an objective response or
    • a CA125 response, in the absence of disease progression by clinical or radiographic criteria
    • sustained stable disease ≥ 3 months by clinical and radiographic criteria


Enrollment: 11
Study Start Date: November 2011
Estimated Study Completion Date: June 2015
Estimated Primary Completion Date: June 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Doxil + BIBF 1120 Drug: Doxil (Pegylated Liposomal Doxorubicin)
Phases I and II: 40 mg/m2 IV over 60 min (+/- 15 min) on day 1 of 28-day cycle
Drug: BIBF 1120

Phase I: Escalating cohorts days -2 through +2, orally 100mg bid, 150mg bid, 200mg bid

Phase II: MTD orally, bid, day 2 of 28-day cycle


Detailed Description:

OUTLINE: This is a phase I/II multi-center study.

Phase I:

All patients will receive a fixed dose of pegylated liposomal doxorubicin (Doxil) of 40 mg/m2 administered IV every 28 days. The dose of BIBF 1120 will be escalated in successive cohorts of patients. A maximum of 12 cycles of combined therapy will be administered corresponding to maximum cumulative dose of PLD of 480 mg/m2. Continuation therapy with single agent BIBF 1120 may continue for selected patients.

The escalation phase will follow the standard 3+3 design. Patients will be accrued to each dose level in cohorts of up to 3-6 evaluable patients. Escalation will continue until a DLT is observed, the highest dose level is reached, or medical judgment indicates. An expansion cohort of 3 to 6 patients will be treated at the MTD (or highest dose level if the MTD is not reached), in order to ensure tolerability of the regimen prior to initiating the Phase II component of the study.

Phase II:

Patients will receive a fixed dose of pegylated liposomal doxorubicin (Doxil) of 40 mg/m2 administered IV every 28 days. Patients will be treated at either dose Level +2 or the MTD dose level of BIBF 1120 as defined by the Phase I cohort. Each cycle will be 28 days. Patients will continue treatment with the combination therapy for a total of up to 12 cycles.

ECOG Performance Status 0-1

Life Expectancy: Not specified

Hematopoietic:

  • Absolute neutrophil count ≥ 1500 cells/mm3
  • White cell blood count ≥ 3000 cells/mm3
  • Hemoglobin ≥ 9.0 g/dL (can be post-transfusion)
  • Platelets ≥ 100,000/mm3 (can not be post-transfusion)

Hepatic:

  • Aspartate aminotransferase and alanine aminotransferase less than or equal to 2.5 times upper limit of normal (ULN)
  • Total serum bilirubin ≤ 1.5 times ULN
  • Alkaline phosphatase ≤ 2.5 times ULN

Renal:

  • Creatinine levels ≤ 1.5 times ULN

Cardiovascular:

  • Baseline left ventricular ejection fraction greater than 50%
  • International Normalized ratio(INR) ≤ 1.5 times ULN, except patients on stable doses of coumadin or low molecular weight heparin NOTE: Patients on stable doses of coumadin or low molecular weight heparin are eligible if anticoagulant doses have been stable and no bleeding complications were recorded.
  • Partial thromboplastin time (PTT) ≤1.5 times ULN
  Eligibility

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

Inclusion Criteria:

  • Platinum-resistant (recurrence within 6 months of a platinum-containing regimen) or platinum refractory (progression while on platinum) disease.
  • Measurable disease as defined by RECIST v1.1 criteria on screening testing
  • Be ≥18 years of age at the time of providing written informed consent for participation.
  • Give written, informed consent for participation in the protocol.
  • Must consent to correlative blood sample collections.
  • Be at least 4 weeks from last treatment to allow recovery from prior toxicity to a Grade 1 or less.
  • The following exceptions are allowed: hormonal therapy - 1 week wash-out; radiation therapy - 3 week wash-out; weekly chemotherapy - 3 week wash-out
  • Patients coming off experimental therapy with biological agents with long half lives (e.g., antibodies) not expected to cause myelotoxicity should be off treatment for at least 4 weeks.
  • Negative serum pregnancy test within 14 days prior to the study entry and be practicing an effective form of contraception if hysterectomy and/or oophorectomy was not part of the prior treatment

Exclusion Criteria:

  • Prior therapy with pegylated liposomal doxorubicin or doxorubicin.
  • Prior therapy with BIBF 1120.
  • Prior anti-angiogenic therapy with tyrosine kinase inhibitors (e.g. sorafenib, sunitinib, others). Note: Prior therapy with bevacizumab is allowed, provided that at least 3 months have elapsed since the last dose of bevacizumab.
  • Grade 2 or greater neuropathy, at time of registration.
  • Active cancer within the last 5 years, with the exception of superficial skin cancer (basal cell or squamous cell skin carcinoma), carcinoma in situ of the cervix, Stage I endometrial cancer with less than 50% invasion of the myometrium, or other adequately treated Stage I or II cancer in complete remission.
  • Presence of active infection requiring antibiotic treatment, at time of registration.
  • Presence of uncontrolled serious medical condition or psychiatric illness as determined by the treating physician, at time of registration.
  • Known history of immune deficiency and be receiving combination anti-retroviral therapy
  • Known or clinically manifest brain metastases, as progressive neurologic dysfunction may develop, that would confound the evaluation of neurologic and other adverse events.
  • Presence of gastrointestinal disorders or abnormalities that would influence the absorption of the study drug.
  • Presence of uncontrolled hypertension, arrhythmia, congestive heart failure or angina, at time of registration. Patients who have had a myocardial infarction or cardiac surgery should be at least 6 months from the event and free of active symptoms.
  • Serious illness or concomitant non-oncological disease such as neurologic, psychiatric, infection disease or laboratory abnormality that may increase the risk associated with study participation or study drug administration.
  • Major injuries within the past 4 weeks prior to start of study treatment with incomplete wound healing and/or planned surgery during the on-treatment study period.
  • History of clinically significant hemorrhagic or thromboembolic event in the past 6 months
  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: NCT01485874

Locations
United States, Indiana
Indiana University Melvin and Bren Simon Cancer Center
Indianapolis, Indiana, United States, 46202
Sponsors and Collaborators
Hoosier Cancer Research Network
Boehringer Ingelheim
Investigators
Principal Investigator: Daniela Matei, M.D. Hoosier Cancer Research Network
  More Information

Additional Information:
No publications provided

Responsible Party: Hoosier Cancer Research Network
ClinicalTrials.gov Identifier: NCT01485874     History of Changes
Other Study ID Numbers: GYN10-149
Study First Received: December 2, 2011
Last Updated: August 20, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Hoosier Cancer Research Network:
BIBF 1120

Additional relevant MeSH terms:
Ovarian Neoplasms
Endocrine Gland Neoplasms
Neoplasms by Site
Neoplasms
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Urogenital Neoplasms
Endocrine System Diseases
Gonadal Disorders
Doxorubicin
Liposomal doxorubicin
Nintedanib
Antibiotics, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 18, 2014