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.
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
