Clinical Trials /

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

NCT01489865

Description:

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.

Related Conditions:
  • Pancreatic Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: ABT-888 With Modified FOLFOX6 in Patients With Metastatic Pancreatic Cancer
  • 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

Clinical Trial IDs

  • ORG STUDY ID: LCCC 2009-608
  • NCT ID: NCT01489865

Conditions

  • Metastatic Pancreatic Cancer

Interventions

DrugSynonymsArms
ABT-888 and mFOLFOX-6ABT-888, 5-Fluorouracil, EloxatinABT-888 and mFOLFOX-6

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.

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.
    

Trial Arms

NameTypeDescriptionInterventions
ABT-888 and mFOLFOX-6ExperimentalABT-888 orally at escalating does in Phase I and then at recommended phase II dose with standard mFOLFOX-6
  • ABT-888 and mFOLFOX-6

Eligibility 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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Dose limiting toxicities
Time Frame:28 days
Safety Issue:
Description:Adverse events will be graded according to NCICTAE version 4

Secondary Outcome Measures

Measure:Objective Response
Time Frame:6 months
Safety Issue:
Description:Complete response + Partial response

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Active, not recruiting
Lead Sponsor:Georgetown University

Trial Keywords

  • Pancreas cancer
  • Veliparib
  • oxaliplatin

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