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NCT Number: NCT01487785

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

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.

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Key information

Conditions

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

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Novartis Investigative Site, Barcelona, Catalonia, Spain

Loading trial locations.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

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.

Primary outcomes

  1. Incidence rate and category of dose limiting toxicities (DLTs)

    Time frame: first 8 weeks of study treatment

    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 outcomes

  1. 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

    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

  2. Plasma pharmacokinetics(PK) parameters of LDE225

    Time frame: baseline, week 9 of the study

    Area Under the Curve (AUC), Maximum observed plasma concentration after drug administration (Cmax), Time to reach Cmax (Tmax), etc.

  3. Plasma pharmacokinetics (PK) of gemcitabine

    Time frame: Baseline, week 9 of the study

    If possible: AUC, Cmax, Tmax, Half life (T1/2), Total body clearance (CL), Apparent volume of distribution at steady state (Vss)

  4. Antitumor efficacy of LDE225+gemcitabine

    Time frame: baseline, week 9 of the study

    Efficacy endpoints (Objective response rate and progression free survival) as a function of Hh target gene expression in tumor samples

  5. Progression free survival

    Time frame: baseline, 8 weeks

    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.

  6. Objective Response Rate

    Time frame: Baseline, 8 weeks

    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

  7. Duration of Response

    Time frame: Baseline, 8 weeks

    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.

  8. Serum tumor marker Ca 19-9

    Time frame: On Day 1 of every cycle (cycle = 28 days)

    the effect of LDE225+gemcitabine on changes overtime in the serum tumor marker Ca 19-9 levels from baseline as assessed by central lab

Sponsors and collaborators

Lead sponsor

Novartis Pharmaceuticals

Industry

Registry information

Official study 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

Important dates

Study start
2012
Primary completion
2014
Study completion
2014
First posted
Dec 7, 2011
Registry last updated
Dec 19, 2020

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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