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

July 31, 2020 updated by: Jeffrey W. Clark, MD, Massachusetts General Hospital

A Phase 1b Clinical Trial of LDE225 in Combination With Fluorouracil, Leucovorin, Oxaliplatin and Irinotecan (FOLFIRINOX) in Previously Untreated Locally Advanced or Metastatic Pancreatic Adenocarcinoma, With an Expansion Cohort at the Recommended Phase 2 Dose

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 Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

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

Study Type

Interventional

Enrollment (Actual)

39

Phase

  • Phase 1

Contacts and Locations

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

Study Locations

  • United States
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • Massachusetts General Hospital
      • Boston, Massachusetts, United States, 02214
        • Dana-Farber Cancer Institute

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.

Eligibility Criteria

Ages Eligible for Study

18 years to 72 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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

Study Plan

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

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

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.
Other Names:
  • 5-FU
  • CPT-11
  • FOLFIRINOX

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

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

Collaborators and Investigators

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

Sponsor

Massachusetts General Hospital

Collaborators

Dana-Farber Cancer Institute

Investigators

  • Principal Investigator: Jeffery W Clark, MD, Massachusetts General Hospital

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 Major Dates

Study Start

December 1, 2011

Primary Completion (Actual)

November 1, 2019

Study Completion (Actual)

November 1, 2019

Study Registration Dates

First Submitted

December 1, 2011

First Submitted That Met QC Criteria

December 2, 2011

First Posted (Estimate)

December 5, 2011

Study Record Updates

Last Update Posted (Actual)

August 4, 2020

Last Update Submitted That Met QC Criteria

July 31, 2020

Last Verified

July 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 11-164

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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