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.

• Status: Terminated
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 23 (actual)
• Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This is an open-label phase 1/2 study that will combine the chemotherapy agents gemcitabine and nab-paclitaxel with an oral hedgehog inhibitor LDE225 (Sonidegib). The objective is to assess tolerability and the resection rate of patients with borderline resectable pancreatic adenocarcinoma who use this 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: 1. 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. 2. 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.

Conditions

• Pancreatic Ductal Adenocarcinoma

Interventions

Type	Name	Description
DRUG	LDE225-600mg	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.
DRUG	Gemcitabine	Four cycles of Gemcitabine 1000 mg/m2 on days 1, 8, and 15 every 28 days.
DRUG	nab-paclitaxel	Four cycles of nab-Paclitaxel 125 mg/m2 on days 1, 8, and 15 every 28 days.
DRUG	LDE225-400mg	Phase I: oral LDE225 (Sonidegib), 400mg daily.
DRUG	LDE225-800mg	Phase I: oral LDE225 (Sonidegib), 800mg daily.

Timeline

• Start date: 2011-12-27
• Primary completion: 2018-11-05
• Completion: 2018-11-05
• First posted: 2011-09-12
• Last updated: 2020-01-22
• Results posted: 2019-06-25

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study