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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

Phase 1/Phase 2
18 Years
Open (Enrolling)
Ovarian Cancer

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Trial Information

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

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

ECOG Performance Status 0-1

Life Expectancy: Not specified


- 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)


- 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


- Creatinine levels ≤ 1.5 times ULN


- 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

- Partial thromboplastin time (PTT) ≤1.5 times ULN

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 v1.0 criteria on screening testing

- Be ≥18 years of age at the time of registration for protocol therapy.

- 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 not expected to cause
myelotoxicity should have been off treatment for at least 4 weeks as wash-out period

- 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

- Known or clinically manifest brain metastases, as progressive neurologic dysfunction
may develop, that would confound the evaluation of neurologic and other adverse

- 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

- 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

Type of Study:


Study Design:

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

Outcome Measure:

Phase I: Safety and Toxicity of Treatment Regimen

Outcome Description:

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.

Outcome Time Frame:

3 months

Safety Issue:


Principal Investigator

Daniela Matei, M.D.

Investigator Role:

Principal Investigator

Investigator Affiliation:

Hoosier Oncology Group


United States: Food and Drug Administration

Study ID:




Start Date:

November 2011

Completion Date:

June 2013

Related Keywords:

  • Ovarian Cancer
  • BIBF 1120
  • Ovarian Neoplasms



Indiana University Melvin and Bren Simon Cancer CenterIndianapolis, Indiana  46202-5289