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

The recruitment status of this study is unknown because the information has not been verified recently.
Verified December 2011 by Massachusetts General Hospital.
Recruitment status was  Recruiting
Dana-Farber Cancer Institute
Information provided by (Responsible Party):
Eunice L. Kwak, MD, PhD, Massachusetts General Hospital
ClinicalTrials.gov Identifier:
First received: December 1, 2011
Last updated: December 20, 2011
Last verified: December 2011
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 Intervention Phase
Pancreatic Cancer
Drug: LDE225; Fluorouracil; Leucovorin; Oxaliplatin; Irinotecan
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:

Further study details as provided by Massachusetts General Hospital:

Primary Outcome Measures:
  • Maximum Tolerated Dose [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
    To determine the maximal tolerated doses of LDE225 in combination with FOLFIRINOX in patients with locally advanced or metastatic pancreatic adenocarcinoma

  • Toxicity [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
    To determine the types, frequency, and severity of adverse events occurring in subjects receiving LDE225 in combination with FOLFIRINOX

Secondary Outcome Measures:
  • Response Rate [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    To determine the response rate of pancreatic cancers treated with LDE225 in combination with FOLFIRINOX

Estimated Enrollment: 40
Study Start Date: December 2011
Estimated Primary Completion Date: September 2013 (Final data collection date for primary outcome measure)
Intervention Details:
    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
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


Ages Eligible for Study:   18 Years to 72 Years
Genders Eligible for Study:   Both
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01485744

Contact: Eunice Kwak, MD, PhD 617-724-4000 ekwak@partners.org

United States, Massachusetts
Massachusetts General Hospital Recruiting
Boston, Massachusetts, United States, 02114
Principal Investigator: Eunice Kwak, MD, PhD         
Dana-Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02214
Principal Investigator: Brian Wolpin, MD         
Sponsors and Collaborators
Massachusetts General Hospital
Dana-Farber Cancer Institute
Principal Investigator: Eunice Kwak, MD, PhD Massachusetts General Hospital
  More Information

Responsible Party: Eunice L. Kwak, MD, PhD, Clinical Director, Developmental Therapeutics, Principal Investigator, Assistant in Medicine, Massachusetts General Hospital
ClinicalTrials.gov Identifier: NCT01485744     History of Changes
Other Study ID Numbers: 11-164 
Study First Received: December 1, 2011
Last Updated: December 20, 2011
Health Authority: United States: Food and Drug Administration

Keywords provided by Massachusetts General Hospital:

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

ClinicalTrials.gov processed this record on May 23, 2016