FOLFIRI or Modified FOLFIRI and Veliparib as Second Line Therapy in Treating Patients With Metastatic Pancreatic Cancer
Condition: Metastatic Pancreatic Adenocarcinoma; Recurrent Pancreatic Carcinoma; Stage IV Pancreatic Cancer AJCC v6 and v7
MeSH terms: Pancreatic Neoplasms
Intervention: Fluorouracil; Fluorouracil; Irinotecan Hydrochloride; Laboratory Biomarker Analysis; Leucovorin Calcium; Veliparib
Intervention description: Given IV; Given IV bolus; Given IV; Correlative studies; Given IV; Given PO
Intervention MeSH terms: Calcium, Dietary; Leucovorin; Folic Acid; Fluorouracil; Irinotecan; Veliparib; Camptothecin; Calcium; Levoleucovorin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 123.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This randomized phase II trial studies how well modified irinotecan hydrochloride, leucovorin
      calcium, fluorouracil (FOLFIRI) and veliparib as a second line of therapy work compared to
      FOLFIRI in treating patients with pancreatic cancer that has come back after a period of
      improvement (metastatic). Drugs used in chemotherapy, such as irinotecan hydrochloride,
      leucovorin calcium, and fluorouracil, work in different ways to stop the growth of tumor
      cells, either by killing the cells, by stopping them from dividing, or by stopping them from
      spreading. Veliparib may stop the growth of tumor cells by blocking some of the enzymes
      needed for cell growth. It is not yet known whether modified FOLFIRI and veliparib as second
      line therapy is more effective than FOLFIRI alone in treating metastatic pancreatic cancer.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients must have histologically or cytologically documented pancreatic
             adenocarcinoma; patients with pancreatic neuroendocrine tumors, lymphoma of the
             pancreas, or ampullary cancer are not eligible

          -  Patients must have metastatic disease that is measurable; computed tomography (CT)
             scans or magnetic resonance imaging (MRI)s used to assess measurable disease must have
             been completed within 28 days prior to registration; CT scans or MRIs used to assess
             non-measurable disease must have been completed within 42 days prior to registration;
             all disease must be assessed and documented on the Baseline Tumor Assessment Form

          -  Patients must not have history of brain metastases

          -  Patients must have had one and only one prior regimen of systemic therapy for
             metastatic disease unless the patient meets the criteria below

          -  Prior systemic therapy and chemoradiotherapy for treatment of resectable, borderline
             resectable or locally advanced unresectable disease is allowed and does not count
             toward prior therapy for metastatic disease

          -  Patients who received systemic therapy with gemcitabine/nab-paclitaxel for resectable
             or borderline/locally advanced unresectable disease and progressed with metastatic
             disease within 3 months of the past dose of systemic therapy are eligible

          -  Patients must have completed systemic therapy at least 14 days prior to registration,
             any surgical procedure must have been performed at least 14 days prior to
             registration, and radiation therapy must be completed at least 7 days prior to
             registration; patients must have recovered from major side effects of prior therapies
             or procedures in the opinion of the local site investigator prior to registration

          -  Patients must not have received prior irinotecan-based chemotherapy (e.g. irinotecan
             hydrochloride, leucovorin calcium, fluorouracil, and oxaliplatin [FOLFIRINOX] or
             FOLFIRI)

          -  Patients must not have received prior PARP inhibitor therapy including, but not
             limited to ABT-888, olaparib, rucaparib, and talazoparib (BMN637)

          -  Patients must have a Zubrod performance status of 0-1

          -  Within 14 days prior to registration: Absolute neutrophil count (ANC) >= 1,500/mcL

          -  Within 14 days prior to registration: Hemoglobin >= 9 g/dL

          -  Within 14 days prior to registration: Platelets >= 100,000/mcL

          -  Within 14 days prior to registration: Total bilirubin =< 1.5 x institutional upper
             limit of normal (IULN)

          -  Within 14 days prior to registration: Serum albumin >= 3.0 g/dL

          -  Within 14 days prior to registration: Aspartate aminotransferase (AST) and alanine
             aminotransferase (ALT) =< 2.5 x IULN; patients with liver metastases may have AST and
             ALT of =< 5.0 x IULN

          -  Within 14 days prior to registration: Serum creatinine =< 2.0 mg/dL

          -  Patients must have CA19-9 obtained within 14 days prior to registration; if CA19-9 is
             normal a carcinoembryonic antigen (CEA) must be tested within 14 days prior to
             registration

          -  Patients must have blood urea nitrogen (BUN), alkaline phosphatase, sodium, potassium,
             calcium, glucose, chloride, and bicarbonate levels obtained within 14 days prior to
             registration

          -  Patients must not have any clinically significant and uncontrolled major medical
             condition(s) including, but not limited to uncontrolled nausea/vomiting/diarrhea;
             active uncontrolled infection; symptomatic congestive heart failure (New York Heart
             Association [NYHA] class >= II); unstable angina pectoris or cardiac arrhythmia;
             psychiatric illness/social situation that would limit compliance with study
             requirements

          -  Patients must not have active seizure or history of seizure

          -  Patients must be able to swallow whole capsule

          -  Patients must have a complete physical examination and medical history within 28 days
             prior to registration

          -  Patients must not have known Gilbert's syndrome

          -  Patients must not have known hypersensitivity to irinotecan, fluorouracil, or
             leucovorin

          -  Patients of childbearing potential must have a negative pregnancy test within 28 days
             prior to registration and must not be nursing; women/men of reproductive potential
             must have agreed to use an effective contraceptive method during the study and for 6
             months following completion of treatment; a woman is considered to be of "reproductive
             potential" if she has had menses at any time in the preceding 12 consecutive months;
             in addition to routine contraceptive methods, "effective contraception" also includes
             heterosexual celibacy and surgery intended to prevent pregnancy (or with a side-effect
             of pregnancy prevention) defined as a hysterectomy, bilateral oophorectomy or
             bilateral tubal ligation; however, if at any point a previously celibate patient
             chooses to become heterosexually active during the time period for use of
             contraceptive measures outlined in the protocol, he/she is responsible for beginning
             contraceptive measures

          -  Patients must be willing and able to undergo a biopsy after signed consent and prior
             to registration; patients must have tumor tissue and blood samples available and be
             willing to submit tumor and blood samples; NOTE: core biopsy required; fine needle
             aspiration (FNA) is not an acceptable substitute for core biopsy

          -  If archival tumor is available for submission, patients must be willing to submit
             tumor sample

          -  Patients must be offered the opportunity to participate in specimen banking for future
             use

          -  Patients must be informed of the investigational nature of this study and must sign
             and give written informed consent in accordance with institutional and federal
             guidelines

          -  As a part of the Oncology Patient Enrollment Network (OPEN) registration process the
             treating institution's identity is provided in order to ensure that the current
             (within 365 days) date of institutional review board approval for this study has been
             entered in the system