Ipilimumab and Gemcitabine Hydrochloride in Treating Patients With Stage III-IV or Recurrent Pancreatic Cancer That Cannot Be Removed by Surgery
Condition: Duct Cell Adenocarcinoma of the Pancreas; Recurrent Pancreatic Cancer; Stage III Pancreatic Cancer; Stage IV Pancreatic Cancer
MeSH terms: Pancreatic Neoplasms
Intervention: ipilimumab; gemcitabine hydrochloride; laboratory biomarker analysis
Intervention description: Given IV; Given IV; Correlative studies
Intervention MeSH terms: Gemcitabine; Ipilimumab; Antineoplastic Agents, Immunological; Antibodies; Immunoglobulins; Antibodies, Monoclonal
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Intervention model: Sequential Assignment
Masking: None (Open Label)
Enrollment: 21.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This phase I trial studies the side effects and best dose of ipilimumab when given together
      with gemcitabine hydrochloride in treating patients with stage III-IV or recurrent pancreatic
      cancer that cannot be removed by surgery. Monoclonal antibodies, such as ipilimumab, can
      block tumor growth in different ways. Some block the ability of tumor cells to grow and
      spread. Others find tumor cells and help kill them or tumor-killing substances to them. Drugs
      used in chemotherapy, such as gemcitabine hydrochloride, work in different ways to kill tumor
      cells or stop them from growing. Giving monoclonal antibody therapy together with
      chemotherapy may kill more tumor cells.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Willing and able to give written informed consent

          -  Histologic or cytologic diagnosis of pancreas adenocarcinoma advanced or recurrent
             (stage III or IV) that is unresectable; histologic or cytologic pathology from any
             prior surgery is sufficient for diagnosis

          -  Must have measurable disease by modified WHO criteria

          -  White blood cells (WBC) >= 2000/uL

          -  Absolute neutrophil count (ANC) >= 1500/uL

          -  Platelets >= 100 x 10^3/uL

          -  Hemoglobin >= 9 g/dL (>= 80 g/L; may be transfused)

          -  Creatinine =< 2.0 x upper limit of normal (ULN)

          -  Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 2.5 x ULN

          -  Bilirubin =< 2.0 x ULN, (except patients with Gilbert's Syndrome, who must have a
             total bilirubin less than 3.0 mg/dL)

          -  No active or chronic infection with human immunodeficiency virus (HIV), hepatitis B,
             or hepatitis C

          -  Performance status: Eastern Cooperative Oncology Group (ECOG) 0-1

          -  Prior systemic therapy for advanced pancreas cancer with gemcitabine is prohibited;
             prior gemcitabine with radiotherapy for localized pancreas cancer is allowed provided
             disease is present outside of the radiated field; prior gemcitabine as adjuvant
             therapy to surgical resection is allowed provided 3 months or greater has elapsed
             between the last dose of gemcitabine and the detection of recurrent disease

          -  Women of childbearing potential (WOCBP) must be using an adequate method of
             contraception to avoid pregnancy throughout the study and for up to 26 weeks after the
             last dose of investigational product, in such a manner that the risk of pregnancy is
             minimized; WOCBP include any female who has experienced menarche and who has not
             undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation,
             or bilateral oophorectomy) or is not post-menopausal; post-menopause is defined as:
             amenorrhea >= 12 consecutive months without another cause, or for women with irregular
             menstrual periods and taking hormone replacement therapy (HRT), a documented serum
             follicle stimulating hormone (FSH) level >= 35 mIU/mL; women who are using oral
             contraceptives, other hormonal contraceptives (vaginal products, skin patches, or
             implanted or injectable products), or mechanical products such as an intrauterine
             device or barrier methods (diaphragm, condoms, spermicides) to prevent pregnancy, or
             are practicing abstinence or where their partner is sterile (eg, vasectomy) should be
             considered to be of childbearing potential

          -  WOCBP must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L
             or equivalent units of human chorionic gonadotrophin [HCG]) within 72 hours before the
             start of ipilimumab

          -  Men of fathering potential must be using an adequate method of contraception to avoid
             conception throughout the study (and for up to 26 weeks after the last dose of
             investigational product) in such a manner that the risk of pregnancy is minimized

          -  Patients on stable anticoagulation are eligible for enrollment; for patients on
             warfarin, prothrombin time (PT)/international normalized ratio (INR) should be
             monitored every 2 weeks during induction therapy, monthly thereafter, or more frequent
             as clinically indicated

        Exclusion Criteria:

          -  Any other malignancy from which the patient has been disease-free for less than 5
             years, with the exception of adequately treated and cured basal or squamous cell skin
             cancer, superficial bladder cancer or carcinoma in situ of the cervix

          -  Autoimmune disease: Patients with a history of inflammatory bowel disease, including
             ulcerative colitis and Crohn's Disease, are excluded from this study, as are patients
             with a history of symptomatic disease (eg, rheumatoid arthritis, systemic progressive
             sclerosis [scleroderma], systemic lupus erythematosus, autoimmune vasculitis [eg,
             Wegener's Granulomatosis]); motor neuropathy considered of autoimmune origin (e.g.
             Guillain-Barre Syndrome and Myasthenia Gravis)

          -  Any underlying medical or psychiatric condition, which in the opinion of the
             investigator will make the administration of ipilimumab hazardous or obscure the
             interpretation of adverse events (AEs), such as a condition associated with frequent
             diarrhea

          -  Any non-oncology vaccine therapy used for prevention of infectious diseases (for up to
             1 month before or after any dose of ipilimumab)

          -  A history of prior treatment with ipilimumab or prior tumor necrosis factor receptor
             superfamily, member 9 (CD137) agonist or cytotoxic T-lymphocyte-associated protein 4
             (CTLA4) inhibitor or agonist

          -  Concomitant therapy with any of the following: interleukin (IL)2, interferon, or other
             non-study immunotherapy regimens; immunosuppressive agents; other investigation
             therapies; or chronic use of systemic corticosteroids

          -  WOCBP who are unwilling or unable to use an acceptable method of contraception to
             avoid pregnancy for their entire study period and for at least 8 weeks after cessation
             of study drug, or have a positive pregnancy test at baseline, or are pregnant or
             breastfeeding

          -  Prisoners or subjects who are compulsorily detained (involuntarily incarcerated) for
             treatment of either a psychiatric or physical (eg, infectious) illness

          -  Patients with symptoms of partial or complete bowel obstruction and recent (within 6
             month) history of fistula, intra-abdominal abscess or bowel perforation

          -  Patients with a history or evidence of central nervous system (CNS) disease, including
             brain tumor, seizures not controlled with standard medical therapy or any brain
             metastases

          -  Patients currently receiving radiation therapy or those having received radiation
             within 4 weeks of study entry

          -  Patients with any known active infection or known history of tuberculosis