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

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2014 by Georgetown University
Sponsor:
Collaborator:
Abbott
Information provided by (Responsible Party):
Georgetown University
ClinicalTrials.gov Identifier:
NCT01489865
First received: December 8, 2011
Last updated: August 13, 2014
Last verified: August 2014
  Purpose

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.


Condition Intervention Phase
Metastatic Pancreatic Cancer
Drug: Veliparib and 5-FU and Oxaliplatin and Leucovorin
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I/II Study of ABT-888 in Combination With 5-fluorouracil and Oxaliplatin (Modified FOLFOX-6) in Patients With Metastatic Pancreatic Cancer

Resource links provided by NLM:


Further study details as provided by Georgetown University:

Primary Outcome Measures:
  • Dose limiting toxicities [ Time Frame: 28 days ] [ Designated as safety issue: Yes ]
    Adverse events will be graded according to NCICTAE version 4


Secondary Outcome Measures:
  • Objective Response [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    Complete response + Partial response


Estimated Enrollment: 48
Study Start Date: February 2011
Estimated Study Completion Date: December 2017
Estimated Primary Completion Date: December 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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
Drug: Veliparib and 5-FU and Oxaliplatin and Leucovorin
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

Detailed Description:

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.

  Eligibility

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

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
  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: NCT01489865

Contacts
Contact: Lisa Ley, RN MSN 202-687-6653 Leyl@georgetown.edu
Contact: Karen Dorsch-Vogel, RN 202-687-6974 kd252@georgetown.edu

Locations
United States, District of Columbia
Georgetown Lombardi Comprehensive Cancer Center Recruiting
Washington, District of Columbia, United States, 20007
Contact: Lisa Ley, RN MSN    202-687-6653    leyl@georgetown.edu   
Contact: Karen Dorsch-Vogel, RN    202-687-6974    kd252@georgetown.edu   
Principal Investigator: Michael Pishvaian, MD PhD         
Sponsors and Collaborators
Georgetown University
Abbott
Investigators
Principal Investigator: Michael Pishvaian, MD PhD Georgetown University
  More Information

No publications provided

Responsible Party: Georgetown University
ClinicalTrials.gov Identifier: NCT01489865     History of Changes
Other Study ID Numbers: LCCC 2009-608
Study First Received: December 8, 2011
Last Updated: August 13, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Georgetown University:
Pancreas cancer
Veliparib
oxaliplatin

Additional relevant MeSH terms:
Pancreatic Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Endocrine Gland Neoplasms
Digestive System Diseases
Pancreatic Diseases
Endocrine System Diseases
Fluorouracil
Oxaliplatin
Leucovorin
Levoleucovorin
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antimetabolites, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Vitamin B Complex
Vitamins
Micronutrients
Growth Substances
Antidotes
Protective Agents

ClinicalTrials.gov processed this record on August 28, 2014