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

Study Overview
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Brief Summary
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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).

Detailed Description
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IPI 926 is an inhibitor of the Hedgehog Pathway. IPI-926 in combination with gemcitabine may improve therapeutic outcomes in patients with pancreatic cancer. Infinity is conducting a Phase 1b/2 clinical trial to evaluate the safety and efficacy of IPI-926 in combination with gemcitabine in patients with previously untreated metastatic pancreatic cancer.

Official Title
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A Phase 1b/2 Study Evaluating IPI-926 in Combination With Gemcitabine in Patients With Metastatic Pancreatic Cancer

Conditions
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Metastatic Pancreatic Cancer

Intervention / Treatment
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* Drug: IPI-926 plus gemcitabine
* Drug: Placebo plus gemcitabine


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Arm 1 (Phase 2)<br>IPI-926 in combination with gemcitabine | Drug: IPI-926 plus gemcitabine<br>* Daily IPI-926 (oral) at 160 mg plus gemcitabine (infusion) at 1000 mg/m2 once weekly for 3 weeks of a 28 day cycle<br>* Other names: Hedgehog;|
| Placebo Comparator: Arm 2 (Phase 2)<br>Placebo in combination with gemcitabine | Drug: IPI-926 plus gemcitabine<br>* Daily IPI-926 (oral) at 160 mg plus gemcitabine (infusion) at 1000 mg/m2 once weekly for 3 weeks of a 28 day cycle<br>* Other names: Hedgehog;Drug: Placebo plus gemcitabine<br>* Daily Oral placebo/IPI-926 160 mg plus gemcitabine infusion at 1000 mg/m2 once every 3 weeks in a 28 day cycle<br>* Other names: Gemzar;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluation of safety profile including MTD | To determine the safety profile, including maximum tolerated dose, of IPI-926 plus gemcitabine in patients with previously untreated metastatic pancreatic cancer. | Once per week for 3 weeks of a 4 week cycle | 
| Overall survival comparison | 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. | An average of 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Measurement of the maximum plasma concentration (Cmax) and area under the concentration versus time curve (AUC0-t) of IPI-926 and gemcitabine. | - To evalutate pharmacokinetics (PK) of IPI-926, gemcitabine, and their relevant metabolites. | During the 3rd week of the first 4 week cycle | 
| Comparison of PFS, TTP and ORR | - 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. | An average of 6 months |