Avastin and Tarceva for Upper Gastrointestinal Cancers

This study has been completed.
Sponsor:
Collaborator:
Aarhus University Hospital
Information provided by:
Rigshospitalet, Denmark
ClinicalTrials.gov Identifier:
NCT00350753
First received: July 10, 2006
Last updated: July 14, 2009
Last verified: July 2009
  Purpose

Erlotinib and bevacizumab have shown activity individually, as single drugs, or in combination with chemotherapy in upper gastro-intestinal cancers, including esophageal and gastro-esophageal adenocarcinomas, gastric cancer and pancreatic cancer. Biomarkers indicating an important role of EGF and VEGF have been found in these tumors, and in cholangiocarcinomas as well. There is promise that combined treatment with erlotinib and bevacizumab is active and tolerable in a broad range of upper gastro-intestinal cancers, justifying an experimental phase II-study of patients with these diagnoses, refractory or intolerant to standard systemic therapy.


Condition Intervention Phase
Cholangiocarcinoma
Gallbladder Cancer
Drug: Erlotinib and bevacizumab
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 II Study of Erlotinib and Bevacizumab in Patients With Advanced Upper Gastrointestinal Carcinomas, Refractory or Intolerable to Standard Systemic Therapy

Resource links provided by NLM:


Further study details as provided by Rigshospitalet, Denmark:

Primary Outcome Measures:
  • Objective response by RECIST criteria [ Time Frame: From time of treatment start to response evaluation ] [ Designated as safety issue: No ]
  • Time to progression [ Time Frame: 1 year ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Toxicity evaluated by NCI-CTCae version 3.0 [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
  • Survival [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  • Biomarkers [ Time Frame: 6 months ] [ Designated as safety issue: No ]

Estimated Enrollment: 126
Study Start Date: June 2006
Study Completion Date: June 2009
Primary Completion Date: June 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Erlotinib and bevacizumab Drug: Erlotinib and bevacizumab
Erlotonib 150 mg daily bevacizumab 10 mg/kg every 14 days

Detailed Description:

Primary Objective

  • To determine the median time to progression (TTP) and response rate (RR) of the combination of erlotinib and bevacizumab in patients with advanced upper gastro-intestinal carcinomas, refractory or intolerant to standard systemic therapy.

Secondary Objective

  • To determine safety, tolerability and toxicity.
  • To determine median and overall survival (OS).
  • To correlate efficacy of treatment with the expression of tumor markers obtained in serum (EFGR, bFGF, p-VEGF-A, and sVEGF-R2), in paraffin embedded tumor tissue (micro vessel density (MVD), and expression of VEGFR and EGFR, after immunostaining), and in fresh frozen tumor biopsies (micro array-based analyses of patterns of gene expression).

Treatment:

Bevacizumab (AvastinÒ) will be given intravenously at 10 mg/kg every other week.

Erlotinib is given as an orally daily dose and most be taken at least one hour before or two hours after ingestion of food.

  Eligibility

Ages Eligible for Study:   18 Months and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologically or cytologically verified carcinoma of the gall bladder or bile ducts.
  • PS 0-1 (ECOG scale)
  • Age > 18 years
  • Life expectancy > 3 months
  • Sufficient organ function, defined as:

    • Platelets > 100 x 109/liter
    • Leukocytes > 3,0 x 109/liter
    • ACN > 1,5 x 109/liter
    • ASAT and/or ALAT < 3 x upper normal limit
    • Bilirubin < 1,5 x upper normal limit
    • EDTA clearance > 45 ml/min
    • APTT and INR < normal limit
  • Fertile females must use oral contraceptive, IUD (intrauterine device) or preservatives. Fertile males must use preservatives.

Exclusion Criteria:

  • Radiotherapy or chemotherapy within the last 4 weeks
  • Co-medication that may interfere with study results; e.g. immuno-suppressive agents other than corticosteroids
  • Any prior EGFR- or VEGFR-based therapy
  • Any condition (medical, social, psychological), which would prevent adequate information and follow-up
  • Tumor located close to major blood vessels and judged to possess a high risk of serious bleeding
  • Any other active malignancy, except basal or squamous cell carcinoma of the skin, or carcinoma in situ
  • Any significant cardiac disease (New York Heart Association Class II or greater), significant arrythmia, congestive heart failure, acute myocardial infarction within 6 months or unstable angina pectoris
  • Clinically significant peripheral vascular disease
  • Evidence of coagulopathy
  • Use of ASA, NSAIDs or clopidogrel
  • Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to treatment, anticipation of need for major surgical procedure during the curse of the study

    o Minor surgical procedures, fine needle aspirations or core biopsies within 7 days prior to treatment

  • History of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess within 6 month prior to treatment
  • Any ongoing infection, uncontrolled diabetes mellitus, serious non-healing wound or ulcer
  • Pregnancy or breast feeding
  • Ongoing therapeutic anti-coagulation
  • Hypertension with blood pressure > 150/100 mmHg
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00350753

Locations
Denmark
Rigshospitalet
Copenhagen, Denmark, 2100
Odense University Hospital
Odense, Denmark, 5000
Århus Sygehus
Århus, Denmark, 8000 C
Sponsors and Collaborators
Rigshospitalet, Denmark
Aarhus University Hospital
Investigators
Principal Investigator: Ulrik Lassen, MD., PH.D. Rigshospitalet, Dept. of Oncology
  More Information

No publications provided

Responsible Party: Ulrik Lassen, Rigshospitalet
ClinicalTrials.gov Identifier: NCT00350753     History of Changes
Other Study ID Numbers: EB-UGI-01, 2006-001308-35
Study First Received: July 10, 2006
Last Updated: July 14, 2009
Health Authority: Denmark: Danish Medicines Agency

Keywords provided by Rigshospitalet, Denmark:
Cholangiocarcinoma

Additional relevant MeSH terms:
Gallbladder Neoplasms
Cholangiocarcinoma
Gastrointestinal Neoplasms
Biliary Tract Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Biliary Tract Diseases
Digestive System Diseases
Gallbladder Diseases
Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Gastrointestinal Diseases
Bevacizumab
Erlotinib
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Pharmacologic Actions
Growth Inhibitors
Antineoplastic Agents
Therapeutic Uses
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on April 22, 2014