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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01485744
Recruitment Status : Active, not recruiting
First Posted : December 5, 2011
Last Update Posted : November 8, 2018
Dana-Farber Cancer Institute
Information provided by (Responsible Party):
Jeffrey W. Clark, MD, Massachusetts General Hospital

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.

Condition or disease Intervention/treatment Phase
Pancreatic Cancer Drug: LDE225; Fluorouracil; Leucovorin; Oxaliplatin; Irinotecan Phase 1

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

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 39 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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 Start Date : December 2011
Estimated Primary Completion Date : March 2019
Estimated Study Completion Date : March 2019

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

Primary Outcome Measures :
  1. 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. Toxicity [ Time Frame: 2 years ]
    To determine the types, frequency, and severity of adverse events occurring in subjects receiving LDE225 in combination with FOLFIRINOX

Secondary Outcome Measures :
  1. Response Rate [ Time Frame: 2 years ]
    To determine the response rate of pancreatic cancers treated with LDE225 in combination with FOLFIRINOX

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 72 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01485744

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United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 02214
Sponsors and Collaborators
Massachusetts General Hospital
Dana-Farber Cancer Institute
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Principal Investigator: Jeffery W Clark, MD Massachusetts General Hospital

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Responsible Party: Jeffrey W. Clark, MD, Physician Hematology/Oncology, Massachusetts General Hospital Identifier: NCT01485744     History of Changes
Other Study ID Numbers: 11-164
First Posted: December 5, 2011    Key Record Dates
Last Update Posted: November 8, 2018
Last Verified: November 2018

Keywords provided by Jeffrey W. Clark, MD, Massachusetts General Hospital:

Additional relevant MeSH terms:
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Pancreatic Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Endocrine Gland Neoplasms
Digestive System Diseases
Pancreatic Diseases
Endocrine System Diseases
Antineoplastic Agents
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs