A Study Evaluating IPI-926 in Combination With Gemcitabine in Patients With Metastatic Pancreatic Cancer

• Evaluation of safety profile including MTD [ Time Frame: Once per week for 3 weeks of a 4 week cycle ]
  To determine the safety profile, including maximum tolerated dose, of IPI-926 plus gemcitabine in patients with previously untreated metastatic pancreatic cancer.
• Overall survival comparison [ Time Frame: An average of 6 months ]
  • To compare the overall survival (OS) of patients with previously untreated metastatic pancreatic cancer treated with IPI-926 plus gemcitabine or placebo plus gemcitabine.
  • To evaluate the safety of IPI-926 plus gemcitabine or placebo plus gemcitabine.

• Measurement of the maximum plasma concentration (Cmax) and area under the concentration versus time curve (AUC0-t) of IPI-926 and gemcitabine. [ Time Frame: During the 3rd week of the first 4 week cycle ]
  - To evalutate pharmacokinetics (PK) of IPI-926, gemcitabine, and their relevant metabolites.
• Comparison of PFS, TTP and ORR [ Time Frame: An average of 6 months ]
  - To compare the progression free survival (PFS), time to progression (TTP) and overall response rate (ORR) of patients treated with IPI-926 plus gemcitabine or placebo plus gemcitabine.

Study IPI-926-03 is a Phase 1b/2 clinical trial to evaluate IPI 926 in combination with gemcitabine in patients with previously untreated metastatic pancreatic cancer. Phase 1b is designed as a dose escalation study. Once the maximum tolerated dose of IPI-926 in combination with gemcitabine is established in the Phase 1b portion of the study, the Phase 2 portion will commence.

Phase 2 is designed as a randomized, double-blind (investigator/patient), placebo-controlled study. There is no cross-over option for patients in either arm of the Phase 2 (i.e., there is no option for patients receiving placebo to cross-over to IPI-926).

• Drug: IPI-926 plus gemcitabine
  Daily IPI-926 (oral) at 160 mg plus gemcitabine (infusion) at 1000 mg/m2 once weekly for 3 weeks of a 28 day cycle
  Other Names:

  • IPI-926
  • Hedgehog pathway inhibitor
  • Hedgehog
• Drug: Placebo plus gemcitabine
  Daily Oral placebo/IPI-926 160 mg plus gemcitabine infusion at 1000 mg/m2 once every 3 weeks in a 28 day cycle
  Other Names:

  • Gemcitabine
  • Hedgehog
  • Hedgehog pathway inhibitor
  • Gemzar

• Active Comparator: Arm 1 (Phase 2)
  IPI-926 in combination with gemcitabine
  Intervention: Drug: IPI-926 plus gemcitabine
• Placebo Comparator: Arm 2 (Phase 2)
  Placebo in combination with gemcitabine
  Interventions:

  • Drug: IPI-926 plus gemcitabine
  • Drug: Placebo plus gemcitabine

Inclusion Criteria:

• 18 years of age
• Pathologically confirmed metastatic pancreatic adenocarcinoma
• At least 1 radiologically evaluable metastatic lesion (RECIST 1.1).
• ECOG 0 or 1
• Life expectancy ≥3 months.
• All women of child bearing potential, all sexually active male patients, and partners of patients must agree to use adequate methods of birth control
• Ability to adhere to the study visit schedule
• Voluntarily signed an informed consent form

Exclusion Criteria:

• Islet cell, acinar cell carcinoma, non-adenocarcinoma, (i.e., lymphoma, sarcoma), adenocarcinoma originated from biliary tree or cystadenocarcinoma
• Prior treatment with chemotherapy for pancreatic cancer.
• Known central nervous system metastases
• Inadequate hematologic function
• Inadequate hepatic function
• Inadequate renal function
• External (percutaneous) biliary drain
• History of stroke, unstable angina, myocardial infarction, or ventricular arrhythmia requiring medication or mechanical control within the last 6 months.
• Venous thromboembolic event (e.g., pulmonary embolism or deep vein thrombosis) requiring anticoagulation not appropriately anticoagulated or have NCI CTCAE Grade 2 or greater bleeding episode in the 3 weeks prior to administration of IPI-926
• Concurrent administration of the medications or foods known to inhibit CYP3A activity to a clinically relevant degree
• Presence of active infection or systemic use of antibiotics within 72 hours of treatment
• Significant co-morbid condition or disease which in the judgment of the Investigator would place the patient at undue risk or interfere with the study.
• Known human immunodeficiency virus (HIV) positivity
• Known hypersensitivity to gemcitabine, IPI-926, or their excipients
• Pregnant or lactating women