- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01431794
Gemcitabine + Nab-paclitaxel With LDE-225 (Hedgehog Inhibitor) as Neoadjuvant Therapy for Pancreatic Adenocarcinoma
Phase 1/2 Safety and Feasibility of Gemcitabine and Nab-Paclitaxel in Combination With LDE-225 as Neoadjuvant Therapy in Patients With Borderline Resectable Pancreatic Adenocarcinoma.
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
The investigators propose treating 6-12 patients during the phase 1 portion and 40 patients in the phase 2 stage.
Phase 1 Stage:
Four cycles of gemcitabine 1000 mg/m2 and nab-paclitaxel 125 mg/m2 on days 1, 8 and 15 in combination with escalating doses (400mg, or 600mg, or 800mg) of LDE-225. After completion of neoadjuvant therapy, the subjects will receive combined chemotherapy and radiation. Then subjects who are eligible for resection will go ahead with surgery. Following resection, subjects will complete two additional cycles of gemcitabine 1000 mg/m2 and nab-paclitaxel 125 mg/m2 in combination with LDE-225.
Phase 2 Stage: In the Phase 2 stage the patients will be randomized to receive gemcitabine and nab-paclitaxel with or without the hedgehog inhibitor LDE225:
- Arm A: Four cycles of gemcitabine 1000 mg/m2 and nab-paclitaxel 125 mg/m on days 1, 8 and 15 in combination with LDE-225 at the recommended phase 2 dose.
- Arm B: Four cycles of gemcitabine 1000 mg/m2 and nab-paclitaxel 125 mg/m on days 1, 8 and 15.
After completion of neoadjuvant therapy, the subjects will receive combined chemotherapy and radiation. Then subjects who are eligible for resection will go ahead with surgery. Following resection, subjects will complete two additional cycles of the pre-surgical therapy.
Several correlative laboratory studies will be conducted during the course of this study. They were designed around the goals of providing us with a better understanding of how the stroma-tumor interaction and the intra-tumoral drug levels of gemcitabine are affected with the use of LDE-225. Two additional biopsies are required to participate in this study.
Study Type
Enrollment (Actual)
Phase
- Phase 2
- Phase 1
Contacts and Locations
Study Locations
-
-
Maryland
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Baltimore, Maryland, United States, 21205
- Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
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-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Histologically or cytologically confirmed adenocarcinoma of the pancreas.
- Must have borderline resectable pancreatic adenocarcinoma
- Measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension
- No previous radiotherapy, surgery, chemotherapy or investigational drug therapy.
- Age >18 years
- Life expectancy of greater than 1 month.
- ECOG (Eastern Cooperative Oncology Group) performance status 0 or 1
- Adequate organ and marrow function
- Asymptomatic for jaundice and ascites. Pain symptoms should be stable.
- Negative serum pregnancy test
- Sexually active males should agree to use a barrier form of contraception, even if they have had a vasectomy, during the study and for 6 months after stopping LDE225. Males should not donate sperm during treatment, and for up to six months after last dose. Sexually active females of child bearing potential agree to using highly effective contraception during study and for 20 months after final dose of LDE225.
- Agree not to donate blood products for 12 months after stopping LDE225.
- Willing to have two biopsies while on treatment for correlative studies.
Exclusion Criteria:
- Patients who have had previous radiotherapy, surgical resection, chemotherapy or investigational drug therapy for pancreatic adenocarcinoma.
- Patient has known metastatic disease.
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to LDE225 or other agents used in the study.
- Patients taking medications with narrow therapeutic indices that are metabolized by cytochrome P450 (CYP450), including warfarin sodium (Coumadin®)
- Uncontrolled illness including, but not limited to, ongoing or active infection requiring IV antibiotics, symptomatic congestive heart failure not controlled with medication, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
- Pregnant women are excluded
- Patient has undergone a major surgery, other than diagnostic surgery within four weeks prior to starting treatment on this study.
- Patients who are receiving treatment with medications known to be moderate and strong inhibitors or inducers of CYP3A4/5 or drugs metabolized by CYP2B6 or CYP2C9 that have narrow therapeutic index, and that cannot be discontinued before starting treatment with LDE225. Medications that are strong CYP3A4/5 inhibitors should be discontinued at least 7 days and strong CYP3A/5 inducers for at least 2 weeks prior to starting treatment with LDE225.
- Patients with neuromuscular disorders.
- Patients with impaired cardiac function.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Phase I-Gem,nab-paclitaxel,LDE225-600mg
Four cycles of Gemcitabine (gem) 1000 mg/m2 and nab-Paclitaxel 125 mg/ m2 on days 1, 8, and 15 every 28 days cycle in combination with escalating doses of oral LDE225 (Sonidegib), 600 mg daily.
|
Phase I: oral LDE225 (Sonidegib), 600mg daily. Phase II Arm A: LDE225 at the recommended phase 2 dose on Days 1, 8 and 15. Cycles repeated every 28 days.
Other Names:
Four cycles of Gemcitabine 1000 mg/m2 on days 1, 8, and 15 every 28 days.
Other Names:
Four cycles of nab-Paclitaxel 125 mg/m2 on days 1, 8, and 15 every 28 days.
Other Names:
|
Active Comparator: Phase II-Arm A:Gem,nab-paclitaxel,LDE225
Four cycles of gemcitabine 1000 mg/m2 and nab-Paclitaxel 125 mg/m2 on days 1, 8 and 15 in combination with LDE-225 at the recommended phase 2 dose.
Cycles repeated every 28 days.
|
Phase I: oral LDE225 (Sonidegib), 600mg daily. Phase II Arm A: LDE225 at the recommended phase 2 dose on Days 1, 8 and 15. Cycles repeated every 28 days.
Other Names:
Four cycles of Gemcitabine 1000 mg/m2 on days 1, 8, and 15 every 28 days.
Other Names:
Four cycles of nab-Paclitaxel 125 mg/m2 on days 1, 8, and 15 every 28 days.
Other Names:
Phase I: oral LDE225 (Sonidegib), 400mg daily.
Other Names:
Phase I: oral LDE225 (Sonidegib), 800mg daily.
Other Names:
|
Active Comparator: Phase II-Arm B:Gem,nab-paclitaxel
Four cycles of gemcitabine 1000 mg/m2 and nab-Paclitaxel 125 mg/m2 on days 1, 8 and 15.
Cycles repeated every 28 days.
|
Four cycles of Gemcitabine 1000 mg/m2 on days 1, 8, and 15 every 28 days.
Other Names:
Four cycles of nab-Paclitaxel 125 mg/m2 on days 1, 8, and 15 every 28 days.
Other Names:
|
Experimental: Phase I-Gem,nab-paclitaxel,LDE225-400mg
Four cycles of Gemcitabine (gem) 1000 mg/m2 and nab-Paclitaxel 125 mg/ m2 on days 1, 8, and 15 every 28 days cycle in combination with escalating doses of oral LDE225 (Sonidegib), 400 mg daily.
|
Four cycles of Gemcitabine 1000 mg/m2 on days 1, 8, and 15 every 28 days.
Other Names:
Four cycles of nab-Paclitaxel 125 mg/m2 on days 1, 8, and 15 every 28 days.
Other Names:
Phase I: oral LDE225 (Sonidegib), 400mg daily.
Other Names:
|
Experimental: Phase I-Gem,nab-paclitaxel,LDE225-800mg
Four cycles of Gemcitabine (gem) 1000 mg/m2 and nab-Paclitaxel 125 mg/ m2 on days 1, 8, and 15 every 28 days cycle in combination with escalating doses of oral LDE225 (Sonidegib), 800 mg daily.
|
Four cycles of Gemcitabine 1000 mg/m2 on days 1, 8, and 15 every 28 days.
Other Names:
Four cycles of nab-Paclitaxel 125 mg/m2 on days 1, 8, and 15 every 28 days.
Other Names:
Phase I: oral LDE225 (Sonidegib), 800mg daily.
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Phase I - Safety and Feasibility of Gemcitabine and Nab-Paclitaxel in Combination With LDE-225 as Neoadjuvant Therapy as Measured by Number of Participants Who Tolerated the Maximal Dose of LDE-225
Time Frame: 5 years
|
Number of participants who tolerated the maximal dose of LDE-225 in combination with gemcitabine, nab-paclitaxel as neoadjuvant therapy in patients with borderline resectable pancreatic adenocarcinoma (PDA).
|
5 years
|
Phase II - Resection Rate of Two Preoperative Chemotherapy Regimens in Patients With Borderline Resectable PDA
Time Frame: 5 years
|
Number of participants with borderline resectable pancreatic adenocarcinoma (PDA) who undergo resection after therapy
|
5 years
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Overall Survival
Time Frame: 5 years
|
Number of months alive from cycle 1, Day 1 until 5 years post-intervention or death, whichever comes first.
|
5 years
|
Overall Tumor Response as Determined by Number of Participants With Complete or Partial Response
Time Frame: 5 years
|
Number of participants who experienced complete response (CR) or partial response (PR), as defined by RECIST v1.0; where CR is a disappearance of all target lesions and PR is ≥30% reduction of target lesions.
|
5 years
|
Collaborators and Investigators
Investigators
- Principal Investigator: Ana De Jesus-Acosta, MD, Sidney Kimmel Comprehensive Cancer Center JHMI
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Neoplasms by Histologic Type
- Neoplasms
- Carcinoma
- Neoplasms, Glandular and Epithelial
- Adenocarcinoma
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Antiviral Agents
- Enzyme Inhibitors
- Antimetabolites, Antineoplastic
- Antimetabolites
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Tubulin Modulators
- Antimitotic Agents
- Mitosis Modulators
- Antineoplastic Agents, Phytogenic
- Gemcitabine
- Paclitaxel
Other Study ID Numbers
- J1130
- NA_00047491 (Other Identifier: JHMIRB)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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