Everolimus, Cetuximab And Capecitabine In Patients With Metastatic Pancreatic Cancer

Study Overview

Everolimus, Cetuximab and Capecitabine in Patients With Metastatic Pancreatic Cancer

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.

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.

Metastatic Pancreatic Cancer

DRUG: Capecitabine
DRUG: Cetuximab
DRUG: Everolimus

AMCmedonc08/345

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2010-02-25	Results First Submitted N/A	Last Update Submitted that met QC Criteria 2021-04-19
First Submitted that Met QC Criteria 2010-03-01	Results First Submitted that Met QC Criteria N/A	Last Update Posted (ACTUAL) 2021-04-21
First Posted (ACTUAL) 2010-03-02	Results First Posted N/A	Last Verified 2021-04

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Design Details

Primary Purpose:
Treatment

Allocation:
Non Randomized

Interventional Model:
Single Group

Masking:
None

Arms and Interventions

Participant Group/Arm	Intervention/Treatment

Primary Outcome Measures	Measure Description	Time Frame
phase I part: assessment of the dose limiting toxicity		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
phase II part: response rate		Assessments after every 3 cycles (9 weeks).

Secondary Outcome Measures	Measure Description	Time Frame
Time to treatment failure		Every 3 months during the first 2 years, and every 6 months thereafter.
Overall survival		Every 3 months during the first 2 years, and every 6 months thereafter.
Toxicity profile		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.
Pharmacodynamics: biomarkers in blood and tumor tissue		Day 1, 8 and 22 during treatment

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

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

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

PRINCIPAL_INVESTIGATOR: Hanneke Wilmink, MD PhD, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

Publications

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

No publications available

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Resources

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Clinical Trial Record