Dose-escalation, and Safety Study of LDE225 and Gemcitabine in Locally Advanced or Metastatic Pancreatic Cancer Patients

NCT01487785 | Completed Phase 1

• 2 other identifiers: CLDE225X21032010-024218-70
• Study Type: interventional
• Target: 18
• Locations: 3 countries
• Sites: 5

Brief Summary

This phase Ib study includes two phases: dose escalation phase and safety expansion phase. During the dose escalation phase, successive cohorts of eligible patients (minimum 3 and maximum 6 evaluable patients per cohort) will receive increasing oral doses of LDE225 administered on a continuous once daily (QD) dose in combination of gemcitabine. This phase of the study will determine the maximum tolerated dose (MTD) and/ or recommended dose for expansion (RDE) of LDE225 administered in combination with gemcitabine in locally advanced or metastatic pancreatic adenocarcinoma patients. During the safety expansion phase, once the MTD of LDE225 is established, additional patients will be enrolled and treated at the MTD of LDE225 in combination with gemcitabine in order to further evaluate its safety, tolerability and explore the potential efficacy of the combined treatments on the patients in locally advanced or metastatic pancreatic adenocarcinoma.

Conditions

Pancreatic Cancer

Keywords

metastatic pancreatic cancer; LDE225; gemcitabine; locally advanced; adenocarcinoma

Outcome Measures

Primary Outcomes (1)

• Incidence rate and category of dose limiting toxicities (DLTs)

  Dose limiting toxicities that occur during the first 8 weeks (56 days) of treatment with LDE225+gemcitabine. Dose limiting toxicity is defined as an adverse event or abnormal laboratory value assessed as unrelated to disease, disease progression, intercurrent illness, or concomitant medications that meets study specific criteria.

  first 8 weeks of study treatment

Secondary Outcomes (8)

• Incidence rate of Adverse Events and Serious Adverse Events

  at Informed Consent Form (ICF) sign off until 120 days after the last dose of study drug

• Plasma pharmacokinetics(PK) parameters of LDE225

  baseline, week 9 of the study

• Plasma pharmacokinetics (PK) of gemcitabine

  Baseline, week 9 of the study

• Antitumor efficacy of LDE225+gemcitabine

  baseline, week 9 of the study

• Progression free survival

  baseline, 8 weeks

Study Arms (1)

LDE225+gemcitabine

EXPERIMENTAL

Increasing doses of LDE225 (from 400 mg) once a day + 1000 mg/m2 of gemcitabine on days 1, 8 and 15 of every 28 day cycle.

Drug: LDE225+gemcitabine

Interventions

LDE225+gemcitabine DRUG

Patients will receive increasing doses of LDE225 (from 400 mg), depending on the cohort they are assigned to, orally once daily and standard doses of gemcitabine (1000 mg/m2) on days 1, 8 and 15 of every 28-day cycle. Patients will receive the study treatment until they progressed, experience unacceptable toxicity, withdraw from the study, or the investigator decides it is in their best interest to discontinue the study treatment.

LDE225+gemcitabine

Eligibility Criteria

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

You may qualify if:

• Patients with locally advanced or metastatic pancreatic adenocarcinoma that have not been previously treated or have progressed despite chemotherapy
• Performance status of 0 or 1 per WHO classification
• Adequate hematologic , renal and liver function
• Adequate blood creatine kinase value (CK \< 1.5ULN)

You may not qualify if:

• Treatment with prior radiotherapy
• Pancreatic cancer that is potentially curable by surgery

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (5)

Massachusetts General Hospital Dept. of Mass General Hospital

Boston, Massachusetts, 02114, United States

Location

Memorial Sloan Kettering Cancer Center MSKCC - SC

New York, New York, 10021, United States

Location

University of Utah / Huntsman Cancer Institute Huntsman UT

Salt Lake City, Utah, 84103, United States

Location

Novartis Investigative Site

Barcelona, Catalonia, 08035, Spain

Location

Novartis Investigative Site

Liverpool, L7 8XP, United Kingdom

Location

Related Links

• Results for CLDE225X2103 can be found on the Novartis Clinical Trial Results Website

MeSH Terms

Conditions

Pancreatic Neoplasms; Adenocarcinoma

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Study Design

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

Study Record Dates

• First Submitted: December 5, 2011
• First Posted: December 7, 2011
• Study Start: March 1, 2012
• Primary Completion: July 1, 2014
• Study Completion: July 1, 2014
• Last Updated: December 19, 2020

Record last verified: 2016-01

Locations

GB (1); ES (1); US (3)