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Gemcitabine

Paclitaxel

Albumin-Bound Paclitaxel

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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.

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.

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 (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 (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.

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.

LDE225-600mg

Four cycles of Gemcitabine 1000 mg/m2 on days 1, 8, and 15 every 28 days.

Four cycles of nab-Paclitaxel 125 mg/m2 on days 1, 8, and 15 every 28 days.

nab-paclitaxel

Phase I: oral LDE225 (Sonidegib), 400mg daily.

LDE225-400mg

Phase I: oral LDE225 (Sonidegib), 800mg daily.

LDE225-800mg

Ana De Jesus-Acosta, MD

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.

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.

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.

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).

Number of participants with borderline resectable pancreatic adenocarcinoma (PDA) who undergo resection after therapy

Number of months alive from cycle 1, Day 1 until 5 years post-intervention or death, whichever comes first.

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.

Novartis Pharmaceuticals

The Skip Viragh Foundation

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Only for eligible participants. There were no participants enrolled in Phase I: gem, nab-paclitaxel, and LDE225-400mg, Phase I: gem, nab-paclitaxel, and LDE225-800mg, Phase II Arm A, and Phase II Arm B because the study was terminated early

Four cycles of Gemcitabine 1000 mg/m2 and nab-Paclitaxel 125 mg/ m2 on days 1, 8, and 15 every 28 days cycle with oral LDE225, 600mg.

Phase I, Gem, Nab-paclitaxel, and LDE225-600mg

Four cycles of Gemcitabine 1000 mg/m2 and nab-Paclitaxel 125 mg/ m2 on days 1, 8, and 15 every 28 days cycle with oral LDE225, 400mg.

Phase I, Gem, Nab-paclitaxel, and LDE225-400mg

Four cycles of Gemcitabine 1000 mg/m2 and nab-Paclitaxel 125 mg/ m2o n days 1, 8, and 15 every 28 days cycle with oral LDE225, 800mg.

Phase I, Gem, Nab-paclitaxel, and LDE225-800mg

Phase II:

Arm A: 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 I dose. Cycles repeated every 28 days.

Phase II, Arm A: Gem, Nab-paclitaxel, and LDE 225

Phase II:

Arm B: Four cycles of gemcitabine 1000 mg/m2 and nab-Paclitaxel 125 mg/m2 on days 1, 8 and 15. Cycles repeated every 28 days.

Phase II, Arm B: Gemcitabine and Nab-paclitaxel

Phase I:

Four cycles of Gemcitabine 1000 mg/m2 and nab-Paclitaxel 125 mg/ m2 on days 1, 8, and 15 every 28 days cycle in combination with oral LDE225 600 mg daily

Phase I:

Four cycles of Gemcitabine 1000 mg/m2 and nab-Paclitaxel 125 mg/ m2 on days 1, 8, and 15 every 28 days cycle in combination with oral LDE225 400 mg daily

Phase I:

Four cycles of Gemcitabine 1000 mg/m2 and nab-Paclitaxel 125 mg/ m2 on days 1, 8, and 15 every 28 days cycle in combination with oral LDE225 800 mg daily

Phase II:

Arm A: 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 from Phase I. Cycles repeated every 28 days.

Total

Age, Continuous

Sex: Female, Male

Not Hispanic or Latino

Race/Ethnicity, Customized

All participants were enrolled in Phase 1, gem, nab-paclitaxel, and LDE225-600mg arm only. Other arms did not have any participants due to the study's early termination.

Dr. Ana De Jesus-Acosta

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: Gem, Nab-paclitaxel, and 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), 400 mg daily.

Phase I: Gem, Nab-paclitaxel, and 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), 800 mg daily.

Phase I: Gem, Nab-paclitaxel, and LDE225-800mg

This measure only applies to the Phase I arms. All 13 subjects participated in the Arm/group: Phase I: gem, nab-paclitaxel, and LDE225-600mg. There were no participants enrolled in other two Arm/group as the study was terminated.

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

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.

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.

Gemcitabine: Four cycles of Gemcitabine 1000 mg/m2 on days 1, 8, and 15 every 28 days.

nab-paclitaxel: Four cycles of nab-Paclitaxel 125 mg/m2 on days 1, 8, and 15 every 28 days.

LDE225-400mg: Phase I: oral LDE225 (Sonidegib), 400mg daily.

LDE225-800mg: Phase I: oral LDE225 (Sonidegib), 800mg daily.

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. Cycles repeated every 28 days.

Gemcitabine: Four cycles of Gemcitabine 1000 mg/m2 on days 1, 8, and 15 every 28 days.

nab-paclitaxel: Four cycles of nab-Paclitaxel 125 mg/m2 on days 1, 8, and 15 every 28 days.

Phase II-Arm B:Gem,Nab-paclitaxel

No data was collected to assess this outcome measure as the study was terminated before Phase II.

Phase II - Resection Rate of Two Preoperative Chemotherapy Regimens in Patients With Borderline Resectable PDA

Overall Survival

Overall Tumor Response as Determined by Number of Participants With Complete or Partial Response

Four cycles of Gemcitabine 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.

Four cycles of Gemcitabine 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 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.

Spots Global Cancer Trial Database for stromal cells