LDE225 With Fluorouracil, Leucovorin, Oxaliplatin, and Irinotecan for Untreated Advanced Pancreatic Cancer
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Purpose
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 |
- 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
- 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) |
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Drug: LDE225; Fluorouracil; Leucovorin; Oxaliplatin; Irinotecan
- FOLFIRINOX
- 5-FU
- CPT-11
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
Eligibility| 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| 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 | |
| Principal Investigator: | Eunice Kwak, MD, PhD | Massachusetts General Hospital |
More Information
No publications provided
| 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:
|
metastatic untreated advanced |
Additional relevant MeSH terms:
|
Pancreatic Neoplasms Digestive System Neoplasms Neoplasms by Site Neoplasms Endocrine Gland Neoplasms Digestive System Diseases Pancreatic Diseases Endocrine System Diseases Fluorouracil Oxaliplatin Irinotecan Leucovorin Levoleucovorin Antimetabolites Molecular Mechanisms of Pharmacological Action |
Pharmacologic Actions Antimetabolites, Antineoplastic Antineoplastic Agents Therapeutic Uses Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs Vitamin B Complex Vitamins Micronutrients Growth Substances Antidotes Protective Agents Antineoplastic Agents, Phytogenic Radiation-Sensitizing Agents |
ClinicalTrials.gov processed this record on May 19, 2013