Gemcitabine Hydrochloride and Cisplatin With or Without Veliparib or Veliparib Alone in Patients With Locally Advanced or Metastatic Pancreatic Cancer

Inclusion Criteria:

• Male or female patients with cytologically or histologically confirmed locally advanced or metastatic pancreas adenocarcinoma with a BRCA1 or 2 or PALB2 mutation confirmed by report from Myriad Genetics (USA); BRCA 1 or 2 or PALB2 mutation can be confirmed locally for all international sites

  • For Part I, non-randomized, lead-in portion, patients with a known BRCA 1 or 2 or PALB2 mutation are eligible along with patients who potentially may have a likelihood of having a BRCA mutation (e.g., personal or family history of breast, pancreas, ovary, endometrial, prostate or other likely related malignancy)

• Patients can have either locally advanced or metastatic pancreas adenocarcinoma for which no prior therapy has been administered for either locally advanced or metastatic disease (Part I [Arms A, B])

  • Prior adjuvant therapy is permissible if gemcitabine or a fluoropyrimidine was administered with or without radiation and if disease recurrence has been documented at least 6 months after completion of adjuvant therapy

• Patients can have either locally advanced or metastatic pancreas adenocarcinoma and received prior therapy (Part II [Arm C])

  • Up to two prior treatment regimens are permissible (excluding a prior PARP inhibitor) for either localized or metastatic pancreas adenocarcinoma
  • Prior combined chemotherapy and radiotherapy is permissible provided the patient has measurable disease outside the radiation port
  • Prior therapy must have been completed at least 3 weeks prior to starting study therapy

• Eastern Cooperative Oncology Group (ECOG) performance status:

  • For Part I (Arm A, B): 0-1 (Karnofsky > 70%)
  • For Part II (Arm C): 0-2 (Karnofsky ≥ 60%)
• Life expectancy of greater than 3 months
• Absolute neutrophil count >= 1,500/mcL
• Hemoglobin >= 9.0 g/dL
• Platelets > 100,000/mcL
• Total bilirubin =< 2 times institutional upper limit of normal (ULN)
• Aspartate aminotransferase/serum glutamic oxaloacetic transaminase (AST/SGOT) and alanine aminotransferase/serum glutamic pyruvate transaminase (ALT/SGPT) < institutional ULN unless there is evidence of liver metastases in which case the AST (SGOT) / ALT (SGPT) must be < 5 times institutional ULN
• Creatinine =< 1.5 x ULN

• Measurable disease by RECIST criteria

  • For the lead-in, non-randomized portion of Part I, either measurable or evaluable disease is acceptable
• If a woman is of child-bearing potential a negative serum or urine pregnancy test is required; women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation
• Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

• Patients who have had chemotherapy or radiotherapy within 3 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 3 weeks earlier

  • For Part I, prior adjuvant therapy with gemcitabine or a fluoropyrimidine therapy is permitted if completed > 6 months prior to recurrence; no prior PARP inhibitor therapy is allowed
  • For Part II, no prior PARP inhibitor therapy is permitted; up to two prior treatment regimens are permitted as follows: 1 adjuvant and 1 metastatic; 1 locally advanced and 1 metastatic; or 2 metastatic, or a variation thereof
• Patients may not be receiving any other investigational agents
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to veliparib or other agents used in study
• For Part I: patients with known contraindications to platinum agents are excluded
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated with veliparib; this may also apply to other agents used in this study

• Patients with an active infection, e.g., hepatitis B virus or hepatitis C virus

  • Human immunodeficiency virus (HIV)-positive patients who are otherwise well and who do not have evidence of significant immune compromise are eligible
• Patients with active seizure or history of seizure are not eligible

• Patients with uncontrolled central nervous system (CNS) metastasis are not eligible

  • Patients with CNS metastases are to be stable for > 3 months after treatment and off steroid treatment prior to study enrollment
• Patients with prior malignancy successfully treated who are currently stable and on no active treatment are eligible
• Patients who are unable to swallow pills/capsules are ineligible