Everolimus, Cetuximab and Capecitabine in Patients With Metastatic Pancreatic Cancer

This study has been completed.
Sponsor:
Information provided by:
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
ClinicalTrials.gov Identifier:
NCT01077986
First received: February 25, 2010
Last updated: May 19, 2014
Last verified: September 2010
  Purpose

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.


Condition Intervention Phase
Metastatic Pancreatic Cancer
Drug: Capecitabine
Drug: Cetuximab
Drug: Everolimus
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA):

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]
  • phase II part: response rate [ Time Frame: Assessments after every 3 cycles (9 weeks). ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Time to treatment failure [ Time Frame: Every 3 months during the first 2 years, and every 6 months thereafter. ] [ Designated as safety issue: No ]
  • Overall survival [ Time Frame: Every 3 months during the first 2 years, and every 6 months thereafter. ] [ Designated as safety issue: No ]
  • 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. ] [ Designated as safety issue: Yes ]
  • Pharmacodynamics: biomarkers in blood and tumor tissue [ Time Frame: Day 1, 8 and 22 during treatment ] [ Designated as safety issue: No ]

Estimated Enrollment: 35
Study Start Date: August 2009
Study Completion Date: August 2011
Primary Completion Date: August 2010 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: Capecitabine
    Capecitabine will be administered for 14 days in a 3 weekly cycle, starting on day 8.
    Other Name: Xeloda
    Drug: Cetuximab
    Cetuximab will be administered weekly, starting at day 8.
    Other Name: Erbitux
    Drug: Everolimus
    Everolimus will be administered daily, starting on day 1.
    Other Name: certican
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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01077986

Locations
Netherlands
Academic Medical Center
Amsterdam, Netherlands, 1105 AZ
Sponsors and Collaborators
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Investigators
Principal Investigator: Hanneke Wilmink, MD PhD Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
  More Information

No publications provided

Responsible Party: J.W. Wilmink, MD PhD, Academisch Medisch Centrum, Universiteit van Amsterdam (AMC-UvA)
ClinicalTrials.gov Identifier: NCT01077986     History of Changes
Other Study ID Numbers: AMCmedonc08/345
Study First Received: February 25, 2010
Last Updated: May 19, 2014
Health Authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Keywords provided by Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA):
mTOR inhibition
EGFR inhibition
pancreatic cancer
pharmacodynamics

Additional relevant MeSH terms:
Pancreatic Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Endocrine Gland Neoplasms
Digestive System Diseases
Pancreatic Diseases
Endocrine System Diseases
Everolimus
Sirolimus
Fluorouracil
Capecitabine
Cetuximab
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Antibiotics, Antineoplastic
Antineoplastic Agents
Antifungal Agents
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on July 31, 2014