Pancreatic cancer
Conditions
Interventions
Trade Name: Abraxane
Pharmaceutical Form: Powder for solution for injection/infusion
INN or Proposed INN: PACLITAXEL
CAS Number: 33069-62-4
Concentration unit: mg milligram(s)
Concentration type: equa
Sponsors
Academic Medical Center
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Patients eligible for inclusion in this study have to fulfill all of the following criteria: 1.patients must provide written informed consent according to ICH/GCP, and national/local regulations prior to any screening procedures. 2. Male or female adult patients (> 18 years) 3. Patients with histologically/cytologically confirmed diagnosis of pancreatic ductal adenocarcinoma. 4. a. Phase I Patients with non resectable or metastasized pancreatic ductal adenocarcinoma 4b. Phase II Patients with non resectable or metastasized pancreatic ductal adenocarcinomanot pre-treated with chemotherapy or radiotherapy unless adjuvant treatment with gemcitabine >6 months 5. Measurable disease as assessed by RECIST 1.1 6. ECOG performance status 0-2 7. Patient has adequate bone marrow and organ function as defined by the following laboratory values: • Absolute Neutrophil Count > 1.5 x 109/L • Hemoglobin > 9.0 g/dL (5.6 mmol/L) • Platelets > 100 x 109/L • Serum total bilirubin within normal range (or = 1.5 x ULN (upper limit of normal); or total bilirubin 60 mL/min/1.73 m2 • Alanine aminotransferase (AST) and aspartate aminotransferase (ALT) within normal range or =65 years) yes F.1.3.1 Number of subjects for this age range 15
Exclusion criteria
Exclusion criteria: 1. Use of other investigational drugs within 30 days of enrollment or 5 half-lives of the study drug, whichever is longer. For investigational biologics enrollment can occur when the expected PD effect has returned to baseline. 2. History of hypersensitivity to LDE225, or to drugs of similar chemical classes. 3. Patient has received previous treatment with smoothened inhibitors. 4. Patients with known CNS metastases or a primary CNS malignancy 5. Patients who have neuromuscular disorders (e.g. inflammatory myopathies, muscular dystrophy, amyotrophic lateral sclerosis and spinal muscular atrophy) or are on concomitant treatment with drugs that are recognized to cause rhabdomyolysis, such as HMG CoA inhibitors (statins), clofibrate and gemfibrozil. If it is essential that the patient remains on a statin to control hyperlipidemia, only Pravastatin may be used with extra caution. 6. Patients who are planning on embarking on new physical activities, such as strenuous exercise, that can result in significant increases in plasma CK levels while on study treatment. 7. Patients who require the use of warfarin (substrate of CYP2C9) cannot be enrolled as LDE225 is a competitive inhibitors of CYP2C9 based on in-vitro data. 8. Patients who are not willing to avoid consumption of Seville oranges, grapefruit or grapefruit juice grapefruit hybrids, pommelos 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. 9. Patients who are not willing to stop taking herbal medications at least 7 days prior to the first dose of study treatment. 10. 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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Phase I To determine the toxicity and optimal dose of LDE225 when co-administered with fixed doses of gemcitabine and nab-paclitaxel in patients with advanced and metastasized pancreatic cancer. Phase II To determine the anti-tumor activity of LDE225 when co-administered with gemcitabine and nab-paclitaxel in patients with advanced and metastasized pancreatic cancer. ;Secondary Objective: To determine survival and progression free survival of LDE 225 in combination with nab-paclitaxel and gemcitabine. ;Primary end point(s): 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. Phase II Response rate according to RECIST 1.1 ;Timepoint(s) of evaluation of this end point: Fase I: coninuously during treatment Fase II: every two months | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Adverse events (AEs ), serious adverse events (SAEs) according to NCI CTC version 4.0 2. Median survival and progression free survival • Changes in vascularity with DCE MRI: Observe the difference in Ktrans between baseline, after 8 weeks of treatment and at tumor progression. • Changes in tumor stroma density with DWI MRI : Observe the difference in AUC between baseline, after 8 weeks of treatment and at tumor progression. 3. Correlation of SPARC (matrix), SMO and Gli (tumor cells) expression in initial tumor biopsy material and CA19.9 (serum) levels during therapy with tumor response. ;Timepoint(s) of evaluation of this end point: 1.continuously during treatment 2. Every two months 3. Baseline | — |
Countries
Netherlands
Contacts
Public ContactEva van Daalen
Academic Medical Center
Outcome results
None listed