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

Primary Purpose

Pancreatic Cancer

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
LDE225; Fluorouracil; Leucovorin; Oxaliplatin; Irinotecan
Sponsored by
Massachusetts General Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Pancreatic Cancer focused on measuring metastatic, untreated, advanced

Eligibility Criteria

18 Years - 72 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Massachusetts General Hospital
  • Dana-Farber Cancer Institute

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

LDE225; Fluorouracil; Leucovorin; Oxaliplatin; Irinotecan

Arm Description

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Response Rate
To determine the response rate of pancreatic cancers treated with LDE225 in combination with FOLFIRINOX

Full Information

First Posted
December 1, 2011
Last Updated
July 31, 2020
Sponsor
Massachusetts General Hospital
Collaborators
Dana-Farber Cancer Institute
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1. Study Identification

Unique Protocol Identification Number
NCT01485744
Brief Title
LDE225 With Fluorouracil, Leucovorin, Oxaliplatin, and Irinotecan for Untreated Advanced Pancreatic Cancer
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
July 2020
Overall Recruitment Status
Completed
Study Start Date
December 2011 (undefined)
Primary Completion Date
November 2019 (Actual)
Study Completion Date
November 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Massachusetts General Hospital
Collaborators
Dana-Farber Cancer Institute

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.
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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pancreatic Cancer
Keywords
metastatic, untreated, advanced

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
39 (Actual)

8. Arms, Groups, and Interventions

Arm Title
LDE225; Fluorouracil; Leucovorin; Oxaliplatin; Irinotecan
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
LDE225; Fluorouracil; Leucovorin; Oxaliplatin; Irinotecan
Other Intervention Name(s)
FOLFIRINOX, 5-FU, CPT-11
Intervention Description
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 Measure Information:
Title
Maximum Tolerated Dose
Description
To determine the maximal tolerated doses of LDE225 in combination with FOLFIRINOX in patients with locally advanced or metastatic pancreatic adenocarcinoma
Time Frame
2 years
Title
Toxicity
Description
To determine the types, frequency, and severity of adverse events occurring in subjects receiving LDE225 in combination with FOLFIRINOX
Time Frame
2 years
Secondary Outcome Measure Information:
Title
Response Rate
Description
To determine the response rate of pancreatic cancers treated with LDE225 in combination with FOLFIRINOX
Time Frame
2 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
72 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jeffery W Clark, MD
Organizational Affiliation
Massachusetts General Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Massachusetts General Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
Dana-Farber Cancer Institute
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02214
Country
United States

12. IPD Sharing Statement

Learn more about this trial

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

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