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

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by National Cancer Institute (NCI)
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT01749397
First received: December 11, 2012
Last updated: September 23, 2014
Last verified: July 2014
  Purpose

This phase I trial studies the side effects and best dose of veliparib when given together with floxuridine in treating patients with metastatic epithelial ovarian, primary peritoneal cavity, or fallopian tube cancer. 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.


Condition Intervention Phase
Recurrent Fallopian Tube Cancer
Recurrent Ovarian Epithelial Cancer
Recurrent Primary Peritoneal Cavity Cancer
Stage IV Fallopian Tube Cancer
Stage IV Ovarian Epithelial Cancer
Stage IV Primary Peritoneal Cavity Cancer
Drug: veliparib
Drug: floxuridine
Other: pharmacological study
Other: laboratory biomarker analysis
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • 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 [ Time Frame: 21 days ] [ Designated as safety issue: Yes ]
    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.


Secondary Outcome Measures:
  • Incidence of adverse events [ Time Frame: Up to 3 months ] [ Designated as safety issue: Yes ]
    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.

  • Incidence of toxicities assessed using CTCAE version 4.0 [ Time Frame: Up to 3 months ] [ Designated as safety issue: Yes ]
    Overall toxicity incidence as well as toxicity profiles by dose level, patient and tumor site will be explored and summarized. Frequency distributions, graphical techniques and other descriptive measures will form the basis of these analyses.

  • Incidence of non-hematologic toxicities evaluated via the CTC standard toxicity grading [ Time Frame: Up to 3 months ] [ Designated as safety issue: Yes ]
    Frequency distributions, graphical techniques and other descriptive measures will form the basis of these analyses.

  • Incidence of hematologic toxicity [ Time Frame: Up to 3 months ] [ Designated as safety issue: Yes ]
    Hematologic toxicity measures of thrombocytopenia, neutropenia, and leukopenia will be assessed using continuous variables as the outcome measures (primarily nadir) as well as categorization via CTC standard toxicity grading. Frequency distributions, graphical techniques and other descriptive measures will form the basis of these analyses.

  • Response profile assessed using Response Evaluation Criteria in Solid Tumors [ Time Frame: Up to 3 months ] [ Designated as safety issue: No ]
    Responses will be summarized by simple descriptive summary statistics delineating complete and partial responses as well as stable and progressive disease in this patient population (overall and by tumor group).

  • Time until any treatment related toxicity [ Time Frame: Up to 3 months ] [ Designated as safety issue: Yes ]
    Will be summarized descriptively.

  • Time until treatment related grade 3+ toxicity [ Time Frame: Up to 3 months ] [ Designated as safety issue: Yes ]
    Will be summarized descriptively.

  • Time until hematologic nadirs (white blood cell, ANC, platelets) [ Time Frame: Up to 3 months ] [ Designated as safety issue: No ]
    Will be summarized descriptively.

  • Time to progression [ Time Frame: Up to 3 months ] [ Designated as safety issue: No ]
    Will be summarized descriptively.

  • Time to treatment failure [ Time Frame: From registration to documentation of progression, unacceptable toxicity, or refusal to continue participation by the patient, assessed up to 3 months ] [ Designated as safety issue: No ]
    Will be summarized descriptively.


Other Outcome Measures:
  • Pharmacokinetic parameters [ Time Frame: 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 ] [ Designated as safety issue: No ]
    Data will be presented in mean and standard deviation in table form.


Estimated Enrollment: 102
Study Start Date: December 2012
Estimated Primary Completion Date: March 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (veliparib and floxuridine)
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: veliparib
Given IV
Other Name: ABT-888
Drug: floxuridine
Given IP
Other Name: 5-FUDR
Other: pharmacological study
Correlative studies
Other Name: pharmacological studies
Other: laboratory biomarker analysis
Correlative studies

Detailed Description:

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.

  Eligibility

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

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
  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: NCT01749397

Locations
United States, Maryland
Johns Hopkins University/Sidney Kimmel Comprehensive Cancer Center Recruiting
Baltimore, Maryland, United States, 21287
Contact: Edward J. Tanner    410-955-8804    jhcccro@jhmi.edu   
Principal Investigator: Edward J. Tanner         
United States, Minnesota
Mayo Clinic Recruiting
Rochester, Minnesota, United States, 55905
Contact: Andrea E. Wahner Hendrickson    507-284-2511    wahnerhendrickson.andrea@mayo.edu   
Principal Investigator: Andrea E. Wahner Hendrickson         
Sponsors and Collaborators
Investigators
Principal Investigator: Andrea Wahner Hendrickson Mayo Clinic
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT01749397     History of Changes
Other Study ID Numbers: NCI-2012-02767, NCI-2012-02767, MC1114, 9182, UM1CA186686, P30CA015083, U01CA069912
Study First Received: December 11, 2012
Last Updated: September 23, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Neoplasms, Glandular and Epithelial
Ovarian Neoplasms
Fallopian Tube Neoplasms
Peritoneal Neoplasms
Neoplasms by Histologic Type
Neoplasms
Endocrine Gland Neoplasms
Neoplasms by Site
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Urogenital Neoplasms
Endocrine System Diseases
Gonadal Disorders
Fallopian Tube Diseases
Abdominal Neoplasms
Digestive System Neoplasms
Digestive System Diseases
Peritoneal Diseases
Floxuridine
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on October 01, 2014