Everolimus, Cetuximab and Capecitabine in Patients With Metastatic Pancreatic Cancer
Primary Purpose
Metastatic Pancreatic Cancer
Status
Completed
Phase
Phase 1
Locations
Netherlands
Study Type
Interventional
Intervention
Capecitabine
Cetuximab
Everolimus
Sponsored by
About this trial
This is an interventional treatment trial for Metastatic Pancreatic Cancer focused on measuring mTOR inhibition, EGFR inhibition, pancreatic cancer, pharmacodynamics
Eligibility Criteria
Inclusion Criteria:
- Signed informed content obtained prior to treatment
- Cytological or histological confirmed adenocarcinoma of the pancreas
- Metastatic pancreatic cancer
- Measurable lesion according to RECIST criteria
- ECOG/ WHO performance 0-2
- Age > 18 years
- Life expectancy > 3 months
- Adequate renal function (creatinine < 150 µmol/L)
- Adequate liver function (bilirubin < 1.5 times upper limit of normal, ALAT or ASAT < 5.0 times upper limit of normal in case of liver metastases and < 2.5 the upper limit of normal in absence of liver metastases
- Adequate bone marrow function (WBC > 3.0 x 10 9/L, platelets > 100 x 10 9/L)
- Mentally, physically, and geographically able to undergo treatment and follow up
Exclusion Criteria:
- Clinical or radiological evidence of CNS metastases
- Pregnancy (positive serum pregnancy test) and lactation
- Serious concomitant systemic disorder that would compromise the safety of the patient, at the discretion of the investigator
- Patients who have any severe and/or uncontrolled medical conditions
- Previous treatment with an mTOR inhibitor
Sites / Locations
- Academic Medical Center
Outcomes
Primary Outcome Measures
phase I part: assessment of the dose limiting toxicity
phase II part: response rate
Secondary Outcome Measures
Time to treatment failure
Overall survival
Toxicity profile
Pharmacodynamics: biomarkers in blood and tumor tissue
Full Information
NCT ID
NCT01077986
First Posted
February 25, 2010
Last Updated
April 19, 2021
Sponsor
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
1. Study Identification
Unique Protocol Identification Number
NCT01077986
Brief Title
Everolimus, Cetuximab and Capecitabine in Patients With Metastatic Pancreatic Cancer
Official Title
A Phase I/ II, Non-randomized, Feasibility/ Safety and Efficacy Study of the Combination of Everolimus, Cetuximab and Capecitabine in Patients With Metastatic Pancreatic Cancer
Study Type
Interventional
2. Study Status
Record Verification Date
April 2021
Overall Recruitment Status
Completed
Study Start Date
August 2009 (undefined)
Primary Completion Date
August 2010 (Actual)
Study Completion Date
August 2011 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
In this study the investigators want to determine the activity and safety of concurrent interruption of the MAPK and PI3K pathways by EGFR and mTOR inhibition in patients with metastatic pancreatic cancer.
Detailed Description
This phase I/II non randomized single center study will be performed as a two step design. Part I is dose finding, whereby dose escalations will be performed for everolimus and capecitabine. Part II is the efficacy study. At the MTD doses in part II biomarker studies will be performed in blood and tumor tissue. Study design phase I part: The first week patients will be treated with everolimus alone. Capecitabine will be administered for 14 days in a 3 weekly cycle, starting on day 8. Cetuximab will be administered weekly, starting at day 8. The dose is fixed for cetuximab during study treatment, whereas the doses of everolimus and capecitabine will differ per dose level. First dose level: Everolimus 5 mg daily continuously, Capecitabine 600 mg/m2 bid for 2 weeks every 3 weeks, Cetuximab 400mg/m2 (120 min infusion) first dose, thereafter 250 mg/m2 (60 min infusion) weekly. Second dose level: Everolimus 10 mg daily continuously, Capecitabine 600 mg/m2 bid for 2 weeks every 3 weeks, Cetuximab 400mg/m2 (120 min infusion) first dose, thereafter 250 mg/m2 (60 min infusion) weekly. Third dose level: Everolimus 10 mg daily continuously, Capecitabine 800 mg/m2 bid for 2 weeks every 3 weeks, Cetuximab 400mg/m2 (120 min infusion) first dose, thereafter 250 mg/m2 (60 min infusion) weekly. Study design phase II part At the MTD 14-25 patients with pancreatic cancer will be included. In the phase II part, everolimus will be administered during one week before start of cetuximab. At day 8 the first dose of cetuximab will be administered. Capecitabine will be started one week thereafter. This enables us to perform pharmacodynamic studies to assess biomarker changes during the different phases of treatment. Everolimus will be administered continuously in a dose of 5 or 10 mg orally once daily (dependent on MTD from part 1). Capecitabine will be administered orally in a dose of 400 - 800 mg/m2 twice daily for 14 days followed by one week rest (dependent on MTD from part 1). Patients will receive cetuximab infusions via an infusion pump, with an initial dose of 400 mg/m² (over 120 min) and subsequent weekly infusions of 250 mg/m² (over 60 min), starting day 8.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Metastatic Pancreatic Cancer
Keywords
mTOR inhibition, EGFR inhibition, pancreatic cancer, pharmacodynamics
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
35 (Actual)
8. Arms, Groups, and Interventions
Intervention Type
Drug
Intervention Name(s)
Capecitabine
Other Intervention Name(s)
Xeloda
Intervention Description
Capecitabine will be administered for 14 days in a 3 weekly cycle, starting on day 8.
Intervention Type
Drug
Intervention Name(s)
Cetuximab
Other Intervention Name(s)
Erbitux
Intervention Description
Cetuximab will be administered weekly, starting at day 8.
Intervention Type
Drug
Intervention Name(s)
Everolimus
Other Intervention Name(s)
certican
Intervention Description
Everolimus will be administered daily, starting on day 1.
Primary Outcome Measure Information:
Title
phase I part: assessment of the dose limiting toxicity
Time Frame
During treatment: assessments on day 1 every cycle (3 weeks). After treatment: every 3 months during the first 2 years, and every 6 months thereafter
Title
phase II part: response rate
Time Frame
Assessments after every 3 cycles (9 weeks).
Secondary Outcome Measure Information:
Title
Time to treatment failure
Time Frame
Every 3 months during the first 2 years, and every 6 months thereafter.
Title
Overall survival
Time Frame
Every 3 months during the first 2 years, and every 6 months thereafter.
Title
Toxicity profile
Time Frame
During treatment: assessments on day 1 every cycle (3 weeks). After treatment: every 3 months during the first 2 years, and every 6 months thereafter.
Title
Pharmacodynamics: biomarkers in blood and tumor tissue
Time Frame
Day 1, 8 and 22 during treatment
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Signed informed content obtained prior to treatment
Cytological or histological confirmed adenocarcinoma of the pancreas
Metastatic pancreatic cancer
Measurable lesion according to RECIST criteria
ECOG/ WHO performance 0-2
Age > 18 years
Life expectancy > 3 months
Adequate renal function (creatinine < 150 µmol/L)
Adequate liver function (bilirubin < 1.5 times upper limit of normal, ALAT or ASAT < 5.0 times upper limit of normal in case of liver metastases and < 2.5 the upper limit of normal in absence of liver metastases
Adequate bone marrow function (WBC > 3.0 x 10 9/L, platelets > 100 x 10 9/L)
Mentally, physically, and geographically able to undergo treatment and follow up
Exclusion Criteria:
Clinical or radiological evidence of CNS metastases
Pregnancy (positive serum pregnancy test) and lactation
Serious concomitant systemic disorder that would compromise the safety of the patient, at the discretion of the investigator
Patients who have any severe and/or uncontrolled medical conditions
Previous treatment with an mTOR inhibitor
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Hanneke Wilmink, MD PhD
Organizational Affiliation
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Official's Role
Principal Investigator
Facility Information:
Facility Name
Academic Medical Center
City
Amsterdam
ZIP/Postal Code
1105 AZ
Country
Netherlands
12. IPD Sharing Statement
Learn more about this trial
Everolimus, Cetuximab and Capecitabine in Patients With Metastatic Pancreatic Cancer
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