Ph1b/2 Study of PF-04136309 in Combination With Gem/Nab-P in First-line Metastatic Pancreatic Patients

• Status: Terminated
• Trial end date: 2017-10-10
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Pfizer
• Treatments: Albumin-Bound Paclitaxel; Gemcitabine; Paclitaxel

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.