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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

Phase 1
18 Years
Open (Enrolling)
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

Thank you

Trial Information

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


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.


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.


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

After completion of study treatment, patients are followed up at 3 months.

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

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

- 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 (ADP-ribose) polymerase (PARP) inhibitor therapy

- Failure to fully recover from acute, reversible effects of prior chemotherapy
regardless of interval since last treatment

- New York Heart Association classification III or IV

- 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

- Significant cardiovascular disease defined as congestive heart failure (New York
Heart Association class II, III or IV), angina pectoris requiring nitrate therapy, or
recent myocardial infarction (=< 6 months prior to registration)

Type of Study:


Study Design:

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

Outcome Measure:

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

Outcome Description:

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.

Outcome Time Frame:

21 days

Safety Issue:


Principal Investigator

Andrea Wahner Hendrickson

Investigator Role:

Principal Investigator

Investigator Affiliation:

Mayo Clinic


United States: Food and Drug Administration

Study ID:




Start Date:

December 2012

Completion Date:

Related Keywords:

  • 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
  • Peritoneal Neoplasms
  • Fallopian Tube Neoplasms
  • Neoplasms, Glandular and Epithelial
  • Ovarian Neoplasms



Johns Hopkins UniversityBaltimore, Maryland  21205
Mayo ClinicRochester, Minnesota  55905