Ph1b/2 Study of PF-04136309 in Combination With Gem/Nab-P in First-line Metastatic Pancreatic Patients
Condition: Metastatic Pancreatic Ductal Adenocarcinoma
MeSH terms: Adenocarcinoma
Intervention: PF-04136309; Nab-paclitaxel; Gemcitabine
Intervention description: PF-04136309 oral dosing; Nab-paclitaxel IV dosing; Gemcitabine IV dosing
Intervention MeSH terms: Paclitaxel; Gemcitabine
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Masking: None (Open Label)
Enrollment: 22.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: CCR2i, nab-paclitaxel, Abraxane, gemcitabine, pancreas

Summary:

      The purpose of this Phase 1b/2 study is to evaluate the safety and tolerability of
      PF-04136309 in combination with nab-paclitaxel and gemcitabine, characterize the
      dose-limiting toxicities (DLTs) and overall safety profile of escalated doses of PF-04136309
      and the associated schedule, determine the maximum tolerated dose (MTD), and to assess the
      enhancement of efficacy of PF-04136309 in combination with nab-paclitaxel and gemcitabine
      versus nab-paclitaxel + gemcitabine + placebo in terms of Progression Free Survival.
    

Eligibility criteria:

        Inclusion Criteria

          1. Histologically or cytologically proven diagnosis of metastatic ductal adenocarcinoma
             of the pancreas.

          2. All patients must provide a baseline tumor sample at registration. If an archival
             sample is not available, patients must have a metastatic biopsy collected at the
             screening visit.

          3. Patient must have received no previous radiotherapy, surgery, chemotherapy or
             investigational therapy for the treatment of metastatic disease.

          4. Measurable disease as per RECIST v. 1.1.

          5. Resolved acute effects of any prior therapy to baseline severity or Grade ≤1 NCI
             CTCAE.

          6. Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0 or 1.

          7. Age ≥18 years.

          8. Adequate Bone Marrow, Renal and liver Functions.

        Exclusion Criteria

          1. Patients with known symptomatic brain metastases requiring steroids.

          2. Prior therapy with modulators of monocyte or TAM function.

          3. Participation in other studies involving investigational drug(s) (Phases 1-4) within 4
             weeks of registering for the current study and/or during study participation.

          4. Diagnosis of any second malignancy within the last 3 years, except for adequately
             treated basal cell carcinoma, or squamous cell skin carcinoma or in situ cervical
             carcinoma.

          5. Known hypersensitivity to nab-paclitaxel or to gemcitabine or to any of the
             excipients.

          6. Any one of the following currently or in the previous 6 months: myocardial infarction,
             severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic
             congestive heart failure, cerebrovascular accident, transient ischemic attack;
             symptomatic pulmonary embolism; congenital long QT syndrome, torsades de points,
             arrhythmias (including sustained ventricular tachyarrhythmia and ventricular
             fibrillation), right bundle branch block and left anterior hemiblock (bifascicular
             block), ongoing cardiac dysrhythmias of NCI CTCAE Grade >=2, atrial fibrillation of
             any grade, or QTc interval >470 msec at screening.

          7. Concurrent administration of herbal preparations.

          8. Use of oral anticoagulants. Use of subcutaneous anti coagulation is allowed.
             Concurrent use of potent or moderate inhibitors or inducers of CYP3A4 and/or CYP2C8.

          9. Active and clinically significant bacterial, fungal or viral infection including
             hepatitis B (HBV), hepatitis C (HCV), known human immunodeficiency virus (HIV) or
             acquired immunodeficiency syndrome (AIDS) related illness.

         10. History of interstitial lung disease, or slowly progressive dyspnea and unproductive
             cough, sarcoidosis, silicosis, idiopathic pulmonary fibrosis, pulmonary
             hypersensitivity pneumonitis or multiple allergies.

         11. Other severe acute or chronic medical or psychiatric condition, including recent
             (within the past year) or active suicidal ideation or behavior) or laboratory
             abnormality that may increase the risk associated with study participation or
             investigational product administration or may interfere with the interpretation of
             study results and, in the judgment of the Investigator, would make the patient
             inappropriate for entry into this study.

         12. Pregnant female patients; breastfeeding female patients; males patients with partners
             currently pregnant, male patients able to father children and female patients of
             childbearing potential who are unwilling or unable to use two (2) highly effective
             methods of contraception as outlined in this protocol for the duration of the study
             and for 28 days after last dose of PF-04136309, and for 6 months after last dose of
             nab-paclitaxel, gemcitabine, or both.

         13. Patients who are investigational site staff members directly involved in the conduct
             of the trial and their family members, site staff members otherwise supervised by the
             Investigator, or patients who are Pfizer employees directly involved in the conduct of
             the trial.