A Phase I Trial of the Combination of the PARP Inhibitor ABT-888 With Intraperitoneal Floxuridine (FUDR) in Epithelial Ovarian, Primary Peritoneal and Fallopian Tube Cancers

Location:

Rochester, Minn.

Trial status:

Open for Enrollment

Why is this study being done?

PRIMARY OBJECTIVES: I. To determine the maximum tolerated dose of the combination of ABT-888 (veliparib) and intraperitoneal (IP) floxuridine in adult patients with advanced ovarian, primary peritoneal or fallopian tube cancer. SECONDARY OBJECTIVES: I. To describe the adverse event profile associated with this treatment combination. II. To assess for preliminary evidence of efficacy, such as tumor responses, of the treatment combination. III. To assess progression free survival (PFS) in the maximum tolerated dose (MTD) cohort. TERTIARY OBJECTIVES: I. Assess the pharmacokinetic profile of ABT-888 and floxuridine when given in combination. II. Assess whether the presence of mutations in the homologous recombination pathway or loss of expression of non-homologous end joining (NHEJ) components correlates with response to floxuridine + ABT-888. OUTLINE: This is a dose-escalation study of veliparib. Patients receive veliparib orally (PO) twice daily (BID) on days 1-10 and floxuridine IP on days 3-5. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up for 3 months.

Who is eligible to participate?

Inclusion Criteria: - Histologically confirmed epithelial ovarian, primary peritoneal or fallopian tube malignancy that is metastatic and for which standard curative measures do not exist - Disease confined to the intraperitoneal and retroperitoneal cavity; note: nodal disease below the diaphragm, implants adherent to the surface of the liver or intrahepatic lesions will not be exclusionary; patients remain eligible if all intrahepatic tumor is debulked at the time of the intraperitoneal catheter placement - EXPANSION PHASE ONLY: Evaluable or measurable disease with the largest nodule measuring less than 5 cm in greatest dimension by radiographic imaging after debulking procedure - Candidate for and willingness to have a surgically placed intraperitoneal catheter and tissue acquisition at the time of port placement; note: if an intraperitoneal catheter is already in place, a tumor biopsy will still be required; a guided core-needle biopsy is sufficient in these cases - Able to swallow and absorb the medication - Absolute neutrophil count (ANC) >= 1500/mm^3 - Platelets (PLT) >= 100,000/mm^3 - Total bilirubin =< 1.5 x institutional upper limit of normal (ULN) - Creatinine =< 1.5 x institutional ULN - Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) =< 3 x institutional ULN - Hemoglobin (Hgb) > 9.0 mg/dl - Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1, or 2 - Ability to provide informed written consent - Life expectancy >= 12 weeks - Women of childbearing potential only: negative pregnancy test done =< 7 days prior to registration Exclusion Criteria: - Known standard therapy for the patient's disease that is potentially curative or definitely capable of extending life expectancy; note: patients with recurrent platinum-sensitive ovarian, primary peritoneal or fallopian tube will be allowed, if the investigator believes the study treatment is a better alternative to initiation platinum-based chemotherapy, such as patients with a prior platinum allergy or low volume disease for whom platinum-based therapy is deferred until a later date - More than 4 prior chemotherapy regimens; note: repeat use of regimens count as 1 prior regimen; switching front-line therapy regimens (for example, from intraperitoneal to intravenous therapy) for reasons other than progression will count as 1 prior therapy; bevacizumab and other 'targeted' agents will count in the total number of prior regimens; vaccine therapies will not count in the total of prior therapies - Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements - Any of the following prior therapies: - Chemotherapy =< 28 days prior to registration - Mitomycin C/nitrosoureas =< 42 days prior to registration - Immunotherapy =< 28 days prior to registration - Biologic therapy =< 28 days prior to registration - Radiation therapy =< 28 days prior to registration - Investigational therapy or any ancillary therapy considered investigational (utilized for a non-Food and Drug Administration [FDA] approved indication and in the context of a research investigation) =< 28 days prior to registration - Prior poly (adenosine diphosphate [ADP]-ribose) polymerase (PARP) inhibitor therapy - Failure to fully recover from acute, reversible effects of prior chemotherapy regardless of interval since last treatment - Significant cardiovascular disease defined as congestive heart failure (New York Heart Association class III or IV cardiac disease), angina pectoris requiring nitrate therapy or recent myocardial infarction (=< 6 months prior to registration) - Metastatic disease outside the intraperitoneal cavity and retroperitoneum, intrahepatic lesions, or pleural effusions; significant ascites precluding catheter placement; exception: intrahepatic lesions removed or planning to be removed during the debulking procedure - Any of the following: - Nursing women - Pregnant women - Women of childbearing potential who are unwilling to employ adequate contraception (non-barrier method) - Immunocompromised patients (other than that related to the use of corticosteroids) with the exception of patients known to be human immunodeficiency virus (HIV) positive and have a cluster of differentiation 4 (CD4) count > 400 and do not require antiretroviral therapy - Receiving any other investigational agent that would be considered a treatment for the primary neoplasm - Other active malignancy =< 1 year prior to registration - EXCEPTIONS: Non-melanotic skin cancer or carcinoma-in-situ of the cervix - NOTE: If there is a history or prior malignancy, they must not be receiving other specific treatment for their cancer

Last updated:

10/2/2014

NCT ID:

NCT01749397

IRB Number:

12-004933