Metastatic Pancreatic Cancer
Conditions
Brief summary
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
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.
Interventions
DRUGIPI-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
DRUGPlacebo 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
Sponsors
Infinity Pharmaceuticals, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Evaluation of safety profile including MTD | 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 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Measurement of the maximum plasma concentration (Cmax) and area under the concentration versus time curve (AUC0-t) of IPI-926 and gemcitabine. | 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 | 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. |
Countries
Canada, United States
Outcome results
None listed