ABT-888 With Modified FOLFOX6 in Patients With Metastatic Pancreatic Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT01489865
Recruitment Status : Recruiting
First Posted : December 12, 2011
Last Update Posted : December 29, 2017
Information provided by (Responsible Party):
Georgetown University

December 8, 2011
December 12, 2011
December 29, 2017
February 2011
December 2018   (Final data collection date for primary outcome measure)
Dose limiting toxicities [ Time Frame: 28 days ]
Adverse events will be graded according to NCICTAE version 4
Same as current
Complete list of historical versions of study NCT01489865 on Archive Site
Objective Response [ Time Frame: 6 months ]
Complete response + Partial response
Same as current
Not Provided
Not Provided
ABT-888 With Modified FOLFOX6 in Patients With Metastatic Pancreatic Cancer
A Phase I/II Study of ABT-888 in Combination With 5-fluorouracil and Oxaliplatin (Modified FOLFOX-6) in Patients With Metastatic Pancreatic Cancer

People are being asked to participate in this study who have metastatic pancreatic cancer (cancer that has spread to other parts of the body).

The purpose of this study is to test the efficacy (effectiveness) of a new combination of drugs, ABT-888 and mFOLFOX-6 (modified 5-Fluorouracil and Oxaliplatin) for patients with metastatic pancreatic cancer.

ABT-888 inhibits an enzyme called "PARP" which helps to fix damaged DNA. By inhibiting this enzyme, ABT-888 prevents cancer cells from repairing the damage caused by the mFOLFOX-6, and will hopefully increase the killing of cancer cells, thus decreasing the tumors in your body.

This is a single arm, open-label Phase I/II study to evaluate the clinical activity of the novel inhibitor of Poly(ADP-ribose) polymerase (PARP), ABT-888 with modified FOLFOX-6 (5-Fluorouracil plus oxaliplatin) in patients with metastatic pancreatic cancer.
Phase 1
Phase 2
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Metastatic Pancreatic Cancer
Drug: ABT-888 and mFOLFOX-6
ABT-888 in escalating doses twice a day for Days 1-7 of each 14-day cycle Oxaliplatin 85 mg/M2 IV on Day 1 Leucovorin 400 mg/m2 IV on Day 1 5-FU 400 mg/m2 IV bolus followed by 2400 mg/m2 IV continuous infusion over 46 hours Days 1-3
Other Names:
  • ABT-888
  • 5-Fluorouracil
  • Eloxatin
Experimental: ABT-888 and mFOLFOX-6
ABT-888 orally at escalating does in Phase I and then at recommended phase II dose with standard mFOLFOX-6
Intervention: Drug: ABT-888 and mFOLFOX-6
Not Provided

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
December 2018
December 2018   (Final data collection date for primary outcome measure)

Inclusion Criteria:

  • Histologically proven pancreatic adenocarcinoma with measurable disease
  • A known BRCA-associate genetic mutation OR family history suggesting of a breast or ovarian cancer syndrome, as defined by one or more of the following:
  • Personal or known family history of a deleterious (or indeterminate) mutation in the BRCA1, BRCA2, PALBB2, or one of the FANC genes.
  • Personal history of breast cancer and one or more of the following:

    • Diagnosed ≤ 45 years old
    • Diagnosed at any age with ≥1 1st, 2nd, or 3rd degree relative with breast cancer ≤ 50 years old and/or ≥1st, 2nd, or 3rd relative with epithelial ovarian cancer at any age
    • Two primary breast cancer with the first diagnosed at ≤ 50 years old
    • Diagnosed ≤ 60 years old with triple negative breast cancer
    • Diagnosed at any age with ≥2 1st, 2nd, or 3rd degree relatives with breast cancer at any age
    • Diagnosed at any age with ≥2 1st, 2nd, or 3rd degree relatives with pancreatic cancer or aggressive prostate cancer (Gleason score ≥7) at any age
    • 1st, 2nd, or 3rd degree male relative with breast cancer
    • Ashkenazi Jewish descent
  • Personal history of epithelial ovarian cancer
  • Personal history of male breast cancer
  • Personal history of pancreatic cancer and ≥2 1st, 2nd, or 3rd degree relatives with breast, epitherlial ovarian, pancreatic, or aggressive prostate cancer (Gleason score ≥7) at any age
  • Age >= 18 years
  • ECOG performance status 0-2
  • Subjects with no brain metastases or a history of previously treated brain metastases who have been treated with surgery or stereotactic radiosurgery at least 4 weeks prior to enrollment and have a baseline MRI that shows no evidence of intercranial disease and have not had treatment with steroids within 1 week of study enrollment.
  • Subjects may have received any number of prior therapies except prior therapy with a PARP inhibitor
  • At least 14 days must have passed since all prior anti-cancer therapy
  • At least 28 days must have passed since any prior antibody-based therapies
  • At least 28 days must have passed since any prior investigational agent
  • All patients must have completely recovered from all transient side effects related to prior therapies and any side effects that are expected to be more durable or permanent must have resolved to Grade 1
  • Adequate hepatic, bone marrow and renal function
  • Partial thromboplastin time must be </= 2 X upper limit of institution's normal range and INR < 2. Subjects on an anticoagulant must have a PTT </= 5 X upper limit of institution's normal range and INR < 5.
  • Life expectancy > 12 weeks
  • Women of childbearing potential must have a negative serum pregnancy test within 14 days prior to initiation of treatment
  • Subject must be capable of understanding and complying with parameters as outlined in protocol and able to sign and date the informed consent form
  • Patients must have fully recovered from all effects of surgery.

Exclusion Criteria:

  • Active severe infection, or known chronic infection with HIV, Hepatitis B virus or Hepatitis C virus
  • Cardiovascular disease problems including unstable angina, therapy for life-threatening ventricular arrhythmia, or myocardial infarction, stroke, or congestive heart failure within the last 6 months
  • Life-threatening visceral disease or other severe concurrent disease
  • Women who are pregnant or breast-feeding
  • Anticipated survival under 3 months
  • The subject has had another active malignancy within the past 5 years except for cervical cancer in situ, in situ carcinoma of the bladder, or non-melanoma carcinoma of the skin.
  • Active uncontrolled infection
  • Symptomatic congestive heart failure
  • Unstable angina pectoris or cardiac arrhythmia
  • Psychiatric illness/ social situation that would limit compliance with study requirements
Sexes Eligible for Study: All
18 Years and older   (Adult, Senior)
Contact: Holly DiFebo, RN MSN 202-687-5760
Contact: Lisa Ley, RN MSN 202-687-6653
United States
LCCC 2009-608
Not Provided
Plan to Share IPD: No
Georgetown University
Georgetown University
Principal Investigator: Michael Pishvaian, MD PhD Georgetown University
Georgetown University
December 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP