Veliparib and Floxuridine in Treating Patients With Metastatic Epithelial Ovarian, Primary Peritoneal Cavity, or Fallopian Tube Cancer

NCT01749397 | Completed Phase 1

• 8 other identifiers: NCI-2012-02767MC11149182P30CA015083P50CA136393U01CA069912UM1CA186686UM1CA186691
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 5

Brief Summary

This phase I trial studies the side effects and best dose of veliparib when given together with floxuridine in treating patients with epithelial ovarian, primary peritoneal cavity, or fallopian tube cancer that has spread to other places in the body. Veliparib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as floxuridine, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving veliparib together with floxuridine may kill more tumor cells.

Conditions

Stage IV Fallopian Tube Cancer AJCC v6 and v7; Stage IV Ovarian Cancer AJCC v6 and v7; Stage IV Primary Peritoneal Cancer AJCC v7

Outcome Measures

Primary Outcomes (1)

• Maximum tolerated dose defined as the dose level below the lowest dose that induces dose-limiting toxicity in at least one-third of patients using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0

  The number and severity of all adverse events (overall, by dose-level, and by tumor group) will be tabulated and summarized in this patient population. The grade 3+ adverse events will also be described and summarized in a similar fashion. This will provide an indication of the level of tolerance for this treatment combination in this patient group.

  21 days

Secondary Outcomes (10)

• Incidence of adverse events

  Up to 3 months

• Incidence of toxicities assessed using CTCAE version 4.0

  Up to 3 months

• Incidence of non-hematologic toxicities evaluated via the CTC standard toxicity grading

  Up to 3 months

• Incidence of hematologic toxicity

  Up to 3 months

• Response profile assessed using Response Evaluation Criteria in Solid Tumors

  Up to 3 months

Other Outcomes (1)

• Pharmacokinetic parameters

  Prior to administration of floxuridine and veliparib, 0.25, 0.5, 1, 2, 4, 6, and 9 hours (day 1 and 3 of course 1), prior to administration of floxuridine and veliparib on days 4-5 of course 1, and prior to administration of veliparib on day 6 course 1

Study Arms (1)

Treatment (veliparib and floxuridine)

EXPERIMENTAL

Patients receive veliparib PO 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.

Drug: Floxuridine; Other: Laboratory Biomarker Analysis; Other: Pharmacological Study; Drug: Veliparib

Interventions

Floxuridine DRUG

Given IP

Also known as: 2''-Deoxy-5-fluorouridine, 5-Fluoro-2''-deoxyuridine, 5-Fluorodeoxyuridine, 5-Fluorouracil deoxyriboside, 5-FUdR, FDUR, Floxuridin, Fluorodeoxyuridine, Fluorouridine Deoxyribose, Fluoruridine Deoxyribose, FUdR, WR-138720

Treatment (veliparib and floxuridine)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (veliparib and floxuridine)

Pharmacological Study OTHER

Correlative studies

Treatment (veliparib and floxuridine)

Veliparib DRUG

Given IV

Also known as: ABT-888, PARP-1 inhibitor ABT-888

Treatment (veliparib and floxuridine)

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically confirmed epithelial ovarian, primary peritoneal or fallopian tube malignancy that is metastatic and for which standard curative measures do not exist
• 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
• Obtained =\< 7 days prior to registration: Absolute neutrophil count (ANC) \>= 1500/mm\^3
• Obtained =\< 7 days prior to registration: Platelets (PLT) \>= 100,000/mm\^3
• Obtained =\< 7 days prior to registration: Total bilirubin =\< 1.5 x institutional upper limit of normal (ULN)
• Obtained =\< 7 days prior to registration: Creatinine =\< 1.5 x institutional ULN
• Obtained =\< 7 days prior to registration: Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) =\< 3 x institutional ULN
• Obtained =\< 7 days prior to registration: 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

You may not qualify if:

• 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:

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (5)

Mayo Clinic in Arizona

Scottsdale, Arizona, 85259, United States

Location

Johns Hopkins University/Sidney Kimmel Cancer Center

Baltimore, Maryland, 21287, United States

Location

Mayo Clinic in Rochester

Rochester, Minnesota, 55905, United States

Location

Siteman Cancer Center at Washington University

St Louis, Missouri, 63110, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

MeSH Terms

Interventions

Floxuridine; 5-fluoro-2'-deoxyuridine; veliparib

Intervention Hierarchy (Ancestors)

Deoxyuridine; Uridine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Andrea E Wahner Hendrickson

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 11, 2012
• First Posted: December 13, 2012
• Study Start: December 7, 2012
• Primary Completion: October 20, 2017
• Study Completion: November 21, 2019
• Last Updated: July 2, 2020

Record last verified: 2020-06

Locations

US (5)