Clinical trial NCT01487785: Dose-escalation, and Safety Study of LDE225 and Gemcitabine in Locally Advanced or Metastatic Pancreatic Cancer Patients
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Pancreatic Cancer
Keywords: metastatic pancreatic cancer
LDE225
gemcitabine
locally advanced
adenocarcinoma
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2011-12-07
Enrollment: 18
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Incidence rate and category of dose limiting toxicities (DLTs)
timeFrame: first 8 weeks of study treatment
Secondary outcomes:
measure: Incidence rate of Adverse Events and Serious Adverse Events
timeFrame: at Informed Consent Form (ICF) sign off until 120 days after the last dose of study drug
measure: Plasma pharmacokinetics(PK) parameters of LDE225
timeFrame: baseline, week 9 of the study
measure: Plasma pharmacokinetics (PK) of gemcitabine
timeFrame: Baseline, week 9 of the study
measure: Antitumor efficacy of LDE225+gemcitabine
timeFrame: baseline, week 9 of the study
measure: Progression free survival
timeFrame: baseline, 8 weeks
measure: Objective Response Rate
timeFrame: Baseline, 8 weeks
measure: Duration of Response
timeFrame: Baseline, 8 weeks
measure: Serum tumor marker Ca 19-9
timeFrame: On Day 1 of every cycle (cycle = 28 days)
Other outcomes:
Locations:
city: Boston
country: United States
facility: Massachusetts General Hospital Dept. of Mass General Hospital
state: Massachusetts
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center MSKCC - SC
state: New York
city: Salt Lake City
country: United States
facility: University of Utah / Huntsman Cancer Institute Huntsman UT
state: Utah
city: Barcelona
country: Spain
facility: Novartis Investigative Site
state: Catalunya
city: Liverpool
country: United Kingdom
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: