NCT02358161

Brief Summary

The 5 year survival of patients with locally advanced or metastatic pancreatic cancer is less than 5 %. Since the introduction of gemcitabine, further advances in therapy in the advanced/metastatic setting have been extremely slow. Numerous phase III studies have evaluated different gemcitabine-based regimens as first-line therapy, but in most cases, any observed benefits have been small and restricted to patients with a good performance status (PS). Recently two new chemotherapy combination schedules, FOLFIRINOX and Gemcitabine + nab-paclitaxel demonstrated a significant survival improvement compared to gemcitabine alone. Nab-paclitaxel is especially interesting because it is able to break-down the tumor matrix and increases the concentration of cytotoxic drugs in the tumor. Our study will explore the modification of the desmoplastic reaction seen in pancreatic cancer using two approaches, targeting tumor stroma by nab-paclitaxel and the hedgehog inhibitor LDE225 and targeting the tumor cells with gemcitabine and nab-paclitaxel.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
78

participants targeted

Target at P75+ for phase_1 pancreatic-cancer

Timeline
Completed

Started Sep 2015

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

April 15, 2014

Completed
10 months until next milestone

First Posted

Study publicly available on registry

February 6, 2015

Completed
7 months until next milestone

Study Start

First participant enrolled

September 1, 2015

Completed
3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

September 1, 2018

Completed
4 months until next milestone

Study Completion

Last participant's last visit for all outcomes

January 1, 2019

Completed
Last Updated

January 9, 2020

Status Verified

January 1, 2020

Enrollment Period

3 years

First QC Date

April 15, 2014

Last Update Submit

January 7, 2020

Conditions

Pancreatic Cancer

Keywords

Pancreatic cancerLDE225Gemcitabinenab paclitaxel

Outcome Measures

Primary Outcomes (1)

  • Dose limiting Toxicity (DLT) and MTD of LDE225 co-administered with gemcitabine and nab-paclitaxel

    Phase I: DLT and MTD of LDE225 co-administered with fixed doses of gemcitabine and nab-paclitaxel in patients with advanced or metastasized pancreatic cancer

    first six weeks after start treatment

Secondary Outcomes (2)

  • Median survival

    1 year

  • Progression free survival

    6 months

Study Arms (1)

LDE225

EXPERIMENTAL

DLT adn MTD of LED225 co-administered with fixed doses of gemcitabine and nab-paclitaxel in patients with advanced or metastasized pancreatic cancer.

Drug: gemcitabine and nab paclitaxel

Interventions

gemcitabine and nab paclitaxelDRUG

DLT adn MTD of LED225 co-administered with fixed doses of gemcitabine and nab-paclitaxel in patients with advanced or metastasized pancreatic cancer

Also known as: Gemzar, Abraxane
LDE225

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Patients must provide written informed consent according to International Conference on Harmonisation of technical requirements for registration og pharmaceuticals for human use (ICH)/Good cClinical Practice (GCP), and national/local regulations prior to any screening procedures.
  • Male or female adult patients (\> 18 years)
  • Patients with histologically/cytologically confirmed diagnosis of pancreatic ductal adenocarcinoma.
  • a. Phase I: patients with non resectable or metastasized pancreatic ductal adenocarcinoma.
  • Measurable disease as assessed by RECIST 1.1 (Response Evaluation Criteria In Solid Tumors) .
  • ECOG (Eastern Cooperative Oncology Group) (WHO) performance status 0-2
  • Patient has adequate bone marrow and organ function . Patient is able to swallow and retain oral medication
  • \. Absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule;

You may not qualify if:

  • History of hypersensitivity to LDE225, or to drugs of similar chemical classes.
  • Patient has received previous treatment with smoothened inhibitors.
  • Patients with known CNS (Central Nervous System) metastases or a primary CNS malignancy.
  • Patients who have neuromuscular disorders or are on concomitant treatment with drugs that are recognized to cause rhabdomyolysis, such as HMG CoA (3-hydroxy-3-methyl-glutaryl Coenzyme A) inhibitors (statins), clofibrate and gemfibrozil.
  • Patients who are planning on embarking on new physical activities, such as strenuous exercise, that can result in significant increases in plasma CK (Creatine Kinase) levels while on study treatment.
  • Patients who require the use of coumarin derivates cannot be enrolled as LDE225 is a competitive inhibitors of CYP2C9 based on in-vitro data.
  • Patients with chronic use of corticosteroids
  • Patients who are not willing to avoid consumption of Seville oranges, grapefruit or grapefruit juice grapefruit hybrids, pomelos and exotic citrus fruits during the entire study and preferably 7 days before the first dose of study medications, due to potential CYP3A4 interaction with the study medications.
  • Patients who are not willing to stop taking herbal medications at least 7 days prior to the first dose of study treatment.
  • Patient is currently being treated with drugs known to be strong inhibitors or inducers of CYP3A4/5, which cannot be discontinued or switched to a different medication 7 days prior to starting study treatment and for the duration of the study..
  • Current medical history of the following:
  • History of or presence of clinically significant uncontrolled ventricular or atrial tachyarrhythmia
  • Clinically significant resting bradycardia (\< 45 beats per minute) or any primary of secondary heart block
  • History of unstable angina pectoris
  • Clinically significant cardio-vascular disease (e.g. congestive heart failure NYHA Class III-IV (New York Heart Association), atherosclerosis, labile hypertension or uncontrolled hypertension
  • +10 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Academic Medical Center

Amsterdam, 1105 AZ, Netherlands

Location

MeSH Terms

Conditions

Pancreatic Neoplasms

Interventions

GemcitabineTaxesAlbumin-Bound Paclitaxel

Condition Hierarchy (Ancestors)

Digestive System NeoplasmsNeoplasms by SiteNeoplasmsEndocrine Gland NeoplasmsDigestive System DiseasesPancreatic DiseasesEndocrine System Diseases

Intervention Hierarchy (Ancestors)

Heterocyclic CompoundsDeoxycytidineCytidinePyrimidine NucleosidesPyrimidinesHeterocyclic Compounds, 1-RingEconomicsHealth Care Economics and OrganizationsPaclitaxelTaxoidsCyclodecanesCycloparaffinsHydrocarbons, AlicyclicHydrocarbons, CyclicHydrocarbonsOrganic ChemicalsDiterpenesTerpenesAlbuminsProteinsAmino Acids, Peptides, and Proteins

Study Officials

  • J. W. Wilmink, MD, PhD

    Academic Medical Center, Medical Oncology

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
M.D., PhD.

Study Record Dates

First Submitted

April 15, 2014

First Posted

February 6, 2015

Study Start

September 1, 2015

Primary Completion

September 1, 2018

Study Completion

January 1, 2019

Last Updated

January 9, 2020

Record last verified: 2020-01

Locations

NL(1)