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

This study has been completed.
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals ) Identifier:
First received: December 5, 2011
Last updated: January 24, 2016
Last verified: January 2016

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.

Condition Intervention Phase
Pancreatic Cancer
Drug: LDE225+gemcitabine
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase Ib, Open-label, Multicenter, Dose-escalation, Safety and Tolerability Study of LDE225 in Combination With Gemcitabine in Patients With Locally Advanced or Metastatic Pancreatic Adenocarcinoma

Resource links provided by NLM:

Further study details as provided by Novartis:

Primary Outcome Measures:
  • Incidence rate and category of dose limiting toxicities (DLTs) [ Time Frame: first 8 weeks of study treatment ] [ Designated as safety issue: No ]
    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.

Secondary Outcome Measures:
  • Incidence rate of Adverse Events and Serious Adverse Events [ Time Frame: at Informed Consent Form (ICF) sign off until 120 days after the last dose of study drug ] [ Designated as safety issue: Yes ]
    Adverse events and serious adverse events, changes in hematology and chemistry values and assessment of physical and neurological examinations, vital signs and electrocardiograms that occur during the reported period

  • Plasma pharmacokinetics(PK) parameters of LDE225 [ Time Frame: baseline, week 9 of the study ] [ Designated as safety issue: No ]
    Area Under the Curve (AUC), Maximum observed plasma concentration after drug administration (Cmax), Time to reach Cmax (Tmax), etc.

  • Plasma pharmacokinetics (PK) of gemcitabine [ Time Frame: Baseline, week 9 of the study ] [ Designated as safety issue: No ]
    If possible: AUC, Cmax, Tmax, Half life (T1/2), Total body clearance (CL), Apparent volume of distribution at steady state (Vss)

  • Antitumor efficacy of LDE225+gemcitabine [ Time Frame: baseline, week 9 of the study ] [ Designated as safety issue: No ]
    Efficacy endpoints (Objective response rate and progression free survival) as a function of Hh target gene expression in tumor samples

  • Progression free survival [ Time Frame: baseline, 8 weeks ] [ Designated as safety issue: No ]
    the effect of LDE225+gemcitabine on progression free survival. Progression Free Survival is defined as the time from date of enrollment to the date of the first documented progression, or death due to any cause, or start of new anti-cancer therapy.

  • Objective Response Rate [ Time Frame: Baseline, 8 weeks ] [ Designated as safety issue: No ]
    The effect of LDE225+gemcitabine on objective response rate. Objective response rate is defined as the proportion of patients with a confirmed complete response (CR) or partial response (PR) as their best overall response per RECIST 1.0

  • Duration of Response [ Time Frame: Baseline, 8 weeks ] [ Designated as safety issue: No ]
    The effect of LDE225+gemcitabine on duration of response. Duration of response is defined as the time from the first occurrence of complete response or partial response until the date of the first documented disease progression or death due to underlying cancer.

  • Serum tumor marker Ca 19-9 [ Time Frame: On Day 1 of every cycle (cycle = 28 days) ] [ Designated as safety issue: No ]
    the effect of LDE225+gemcitabine on changes overtime in the serum tumor marker Ca 19-9 levels from baseline as assessed by central lab

Enrollment: 18
Study Start Date: March 2012
Study Completion Date: July 2014
Primary Completion Date: July 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: LDE225+gemcitabine
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
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.


Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • 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)

Exclusion Criteria:

  • Treatment with prior radiotherapy
  • Pancreatic cancer that is potentially curable by surgery
  • Women of childbearing potential unless they are using highly effective method of contraception Other protocol-defined inclusion/exclusion criteria may apply

Other protocol-defined inclusion/exclusion criteria may apply.

  Contacts and Locations
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Please refer to this study by its identifier: NCT01487785

United States, Massachusetts
Massachusetts General Hospital Dept. of Mass General Hospital
Boston, Massachusetts, United States, 02114
United States, New York
Memorial Sloan Kettering Cancer Center MSKCC - SC
New York, New York, United States, 10021
United States, Utah
University of Utah / Huntsman Cancer Institute Huntsman UT
Salt Lake City, Utah, United States, 84103
Novartis Investigative Site
Barcelona, Catalunya, Spain, 08035
United Kingdom
Novartis Investigative Site
Liverpool, United Kingdom, L7 8XP
Sponsors and Collaborators
Novartis Pharmaceuticals
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

Responsible Party: Novartis ( Novartis Pharmaceuticals ) Identifier: NCT01487785     History of Changes
Other Study ID Numbers: CLDE225X2103  2010-024218-70 
Study First Received: December 5, 2011
Last Updated: January 24, 2016
Health Authority: United States: Food and Drug Administration
United Kingdom: Medicines and Healthcare Products Regulatory Agency
Spain: Agencia Española de Medicamentos y Productos Sanitarios

Keywords provided by Novartis:
metastatic pancreatic cancer
locally advanced

Additional relevant MeSH terms:
Pancreatic Neoplasms
Digestive System Diseases
Digestive System Neoplasms
Endocrine Gland Neoplasms
Endocrine System Diseases
Neoplasms by Site
Pancreatic Diseases
Anti-Infective Agents
Antimetabolites, Antineoplastic
Antineoplastic Agents
Antiviral Agents
Enzyme Inhibitors
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs processed this record on May 26, 2016