LDE225 With Fluorouracil, Leucovorin, Oxaliplatin, And Irinotecan For Untreated Advanced Pancreatic Cancer

Study Overview

LDE225 With Fluorouracil, Leucovorin, Oxaliplatin, and Irinotecan for Untreated Advanced Pancreatic Cancer

LDE225 is a new medicine that blocks the Hedgehog (Hh) pathway. The Hh pathway is a cascade of molecular events that control cell growth and have been linked with the development of many human cancers, including pancreatic cancer. Information from research studies suggests that LDE225 in combination with FOLFIRINOX may help to stop the growth of cancer cells. In this research study, the investigators are looking to determine the maximum dose of LDE225 in combination that can be given safely to patients with locally advanced or metastatic pancreatic cancer.

Study medication will be given in cycles of 14 days. Subjects will keep a study drug diary for each treatment cycle. LDE225 capsules will be taken by mouth in the morning every day of each cycle. On days 1-2 of each cycle, subjects will take LDE225 at the clinic followed by FOLFIRINOX intravenous infusion (through a vein). Subjects will come to the clinic weekly for the first 5 weeks, then every other week (Week 7, 9, 11, etc.) and receive the following procedures: Review of current medications and any side effects Physical exam Performance Status Blood tests (2 teaspoons of blood) Assessment of tumor (repeated every 8 weeks) ECG at week 3 and 5 Subjects will also have pharmacokinetic (PK) blood samples taken. PK samples are used to find out the amount of study medication in the blood. Each PK sample is about 1/2 teaspoon of blood. Subjects will have PK samples taken on: Day 1 of Cycles 1, 2, 3, 4, 6, and 7 before the dose of LDE225 Day 1 of Cycle 5 - drawn before the first dose of LDE225 and at 1, 2, 3, 4, 5, and 6 hours Day 2 of Cycle 5: One PK blood sample

Pancreatic Cancer

DRUG: LDE225; Fluorouracil; Leucovorin; Oxaliplatin; Irinotecan

11-164

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2011-12-01	Results First Submitted N/A	Last Update Submitted that met QC Criteria 2020-07-31
First Submitted that Met QC Criteria 2011-12-02	Results First Submitted that Met QC Criteria N/A	Last Update Posted (ACTUAL) 2020-08-04
First Posted (ACTUAL) 2011-12-05	Results First Posted N/A	Last Verified 2020-07

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Design Details

Primary Purpose:
Treatment

Allocation:
Na

Interventional Model:
Single Group

Masking:
None

Arms and Interventions

Participant Group/Arm	Intervention/Treatment
EXPERIMENTAL: LDE225; Fluorouracil; Leucovorin; Oxaliplatin; Irinotecan	DRUG: LDE225; Fluorouracil; Leucovorin; Oxaliplatin; Irinotecan LDE225 200-800 mg daily orally. Fluorouracil 2400 mg IV every other week. Irinotecan 180 mg/m2 IV every other week. Oxaliplatin 85 mg/m2 IV every other week. Leucovorin 400 mg/m2 IV every other week.

Participant Group/Arm

Intervention/Treatment

EXPERIMENTAL: LDE225; Fluorouracil; Leucovorin; Oxaliplatin; Irinotecan

DRUG: LDE225; Fluorouracil; Leucovorin; Oxaliplatin; Irinotecan

LDE225 200-800 mg daily orally. Fluorouracil 2400 mg IV every other week. Irinotecan 180 mg/m2 IV every other week. Oxaliplatin 85 mg/m2 IV every other week. Leucovorin 400 mg/m2 IV every other week.

Primary Outcome Measures	Measure Description	Time Frame
Maximum Tolerated Dose	To determine the maximal tolerated doses of LDE225 in combination with FOLFIRINOX in patients with locally advanced or metastatic pancreatic adenocarcinoma	2 years
Toxicity	To determine the types, frequency, and severity of adverse events occurring in subjects receiving LDE225 in combination with FOLFIRINOX	2 years

Secondary Outcome Measures	Measure Description	Time Frame
Response Rate	To determine the response rate of pancreatic cancers treated with LDE225 in combination with FOLFIRINOX	2 years

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

Histologically or cytologically confirmed locally advanced or metastatic pancreatic adenocarcinoma
Previously untreated locally advanced or metastatic pancreatic adenocarcinoma. Pts newly diagnosed with metastatic recurrence after adjuvant therapy for resected disease are eligible, if completion of adjuvant therapy was > 8 months ago
Measurable disease
Adequate organ and marrow function
Able to take oral drugs

Concurrent active primary or metastatic cancer other than superficial squamous cell or basal cell skin cancer
Pregnant or breastfeeding
Receiving any other standard or investigation anticancer agents, with the exception of hormonal therapy
Prior chemoradiation to the primary pancreatic tumor unless there is a measurable distant site of disease
Known CNS metastases
History of hypersensitivity reactions to any components of the treatment regimen
Known malabsorption syndromes
Neuromuscular disorders
Receiving other anti-neoplastic therapy concurrently
Requires warfarin/Coumadin for therapeutic coagulation
Receiving treatment with medications known to be moderate and strong inhibitors or inducers of CYP3A4/5
Uncontrolled diarrhea
Peripheral neuropathy > grade 1 due to any cause
Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia other than chronic atrial fibrillation, or psychiatric illness/social situations that would limit compliance with study requirements
HIV positive

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Dana-Farber Cancer Institute

Investigators

PRINCIPAL_INVESTIGATOR: Jeffery W Clark, MD, Massachusetts General Hospital

Publications

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

No publications available

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Resources

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Caregivers

Clinical Trial Record