Gemcitabine + Nab-paclitaxel With LDE-225 (Hedgehog Inhibitor) as Neoadjuvant Therapy for Pancreatic Adenocarcinoma

NCT01431794 | Terminated Phase 1 Results DMC FDA Drug

• 2 other identifiers: J1130NA_00047491
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Pancreatic Ductal Adenocarcinoma

Keywords

Pancreatic ductal adenocarcinoma (PDA)Neoplasms; LDE225; nab-paclitaxel; abraxane; gemcitabine; neoadjuvant; cytotoxic; hedgehog inhibitor; stromal cells; resectable PDA; Pancreatic Diseases; Carcinoma; Sonidegib

Outcome Measures

Primary Outcomes (2)

• 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

  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

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

  5 years

Secondary Outcomes (2)

• Overall Survival

  5 years

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

  5 years

Study Arms (5)

Phase I-Gem,nab-paclitaxel,LDE225-600mg

EXPERIMENTAL

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.

Drug: LDE225-600mg; Drug: Gemcitabine; Drug: nab-paclitaxel

Phase II-Arm A:Gem,nab-paclitaxel,LDE225

ACTIVE COMPARATOR

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.

Drug: LDE225-600mg; Drug: Gemcitabine; Drug: nab-paclitaxel; Drug: LDE225-400mg; Drug: LDE225-800mg

Phase II-Arm B:Gem,nab-paclitaxel

ACTIVE COMPARATOR

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

Drug: Gemcitabine; Drug: nab-paclitaxel

Phase I-Gem,nab-paclitaxel,LDE225-400mg

EXPERIMENTAL

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.

Drug: Gemcitabine; Drug: nab-paclitaxel; Drug: LDE225-400mg

Phase I-Gem,nab-paclitaxel,LDE225-800mg

EXPERIMENTAL

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.

Drug: Gemcitabine; Drug: nab-paclitaxel; Drug: LDE225-800mg

Interventions

LDE225-600mg DRUG

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.

Also known as: Sonidegib

Phase I-Gem,nab-paclitaxel,LDE225-600mg; Phase II-Arm A:Gem,nab-paclitaxel,LDE225

Gemcitabine DRUG

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

Also known as: gem

Phase I-Gem,nab-paclitaxel,LDE225-400mg; Phase I-Gem,nab-paclitaxel,LDE225-600mg; Phase I-Gem,nab-paclitaxel,LDE225-800mg; Phase II-Arm A:Gem,nab-paclitaxel,LDE225; Phase II-Arm B:Gem,nab-paclitaxel

nab-paclitaxel DRUG

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

Also known as: abraxane

Phase I-Gem,nab-paclitaxel,LDE225-400mg; Phase I-Gem,nab-paclitaxel,LDE225-600mg; Phase I-Gem,nab-paclitaxel,LDE225-800mg; Phase II-Arm A:Gem,nab-paclitaxel,LDE225; Phase II-Arm B:Gem,nab-paclitaxel

LDE225-400mg DRUG

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

Also known as: Sonidegib

Phase I-Gem,nab-paclitaxel,LDE225-400mg; Phase II-Arm A:Gem,nab-paclitaxel,LDE225

LDE225-800mg DRUG

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

Also known as: Sonidegib

Phase I-Gem,nab-paclitaxel,LDE225-800mg; Phase II-Arm A:Gem,nab-paclitaxel,LDE225

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins: lead
• Novartis Pharmaceuticals: collaborator
• The Skip Viragh Foundation: collaborator

Study Sites (1)

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Baltimore, Maryland, 21205, United States

Location

MeSH Terms

Conditions

Pancreatic Diseases; Carcinoma

Interventions

sonidegib; Gemcitabine; 130-nm albumin-bound paclitaxel; Albumin-Bound Paclitaxel

Condition Hierarchy (Ancestors)

Digestive System Diseases; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Paclitaxel; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Albumins; Proteins; Amino Acids, Peptides, and Proteins

Results Point of Contact

• Title: Dr. Ana De Jesus-Acosta
• Organization: Johns Hopkins University School of Medicine

adejesu1@jhmi.edu

443-287-0411

Study Officials

• Ana De Jesus-Acosta, MD

  Sidney Kimmel Comprehensive Cancer Center JHMI

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 19, 2011
• First Posted: September 12, 2011
• Study Start: December 27, 2011
• Primary Completion: November 5, 2018
• Study Completion: November 5, 2018
• Last Updated: January 22, 2020
• Results First Posted: June 25, 2019

Record last verified: 2020-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)