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

NCT01485744 | Completed Phase 1 DMC

• 1 other identifier: 11-164
• Study Type: interventional
• Target: 39
• Locations: 1 country
• Sites: 2

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.

Conditions

Pancreatic Cancer

Keywords

metastatic; untreated; advanced

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (1)

• Response Rate

  2 years

Study Arms (1)

LDE225; Fluorouracil; Leucovorin; Oxaliplatin; Irinotecan

EXPERIMENTAL

Drug: LDE225; Fluorouracil; Leucovorin; Oxaliplatin; Irinotecan

Interventions

LDE225; Fluorouracil; Leucovorin; Oxaliplatin; Irinotecan DRUG

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.

Also known as: FOLFIRINOX, 5-FU, CPT-11

LDE225; Fluorouracil; Leucovorin; Oxaliplatin; Irinotecan

Eligibility Criteria

• Age: 18 Years - 72 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Massachusetts General Hospital: lead
• Dana-Farber Cancer Institute: collaborator

Study Sites (2)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02214, United States

Location

MeSH Terms

Conditions

Pancreatic Neoplasms; Neoplasm Metastasis

Interventions

sonidegib; Fluorouracil; Leucovorin; Oxaliplatin; Irinotecan; folfirinox

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes; Coordination Complexes; Organic Chemicals; Camptothecin; Alkaloids

Study Officials

• Jeffery W Clark, MD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Physician Hematology/Oncology

Study Record Dates

• First Submitted: December 1, 2011
• First Posted: December 5, 2011
• Study Start: December 1, 2011
• Primary Completion: November 1, 2019
• Study Completion: November 1, 2019
• Last Updated: August 4, 2020

Record last verified: 2020-07

Locations

US (2)