Avastin and Tarceva for Upper Gastrointestinal Cancers - Full Text View

Sponsor:	Rigshospitalet, Denmark
Collaborator:	Morten Ladekarl, MD, DMSc.,Dept. of Oncology, Århus University Hospital, Denmark
Information provided by:	Rigshospitalet, Denmark
ClinicalTrials.gov Identifier:	NCT00350753

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 II

Study Type:	Interventional
Study Design:	Treatment, Non-Randomized, Open Label, Uncontrolled, Single Group Assignment, Safety/Efficacy Study
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:

MedlinePlus related topics: Cancer Gallbladder Cancer

Drug Information available for: Erlotinib hydrochloride Erlotinib Bevacizumab

U.S. FDA Resources

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
Erlotinib and bevacizumab: Experimental	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
Århus Sygehus
Århus, Denmark, 8000 C
Odense University Hospital
Odense, Denmark, 5000

Sponsors and Collaborators

Rigshospitalet, Denmark

Morten Ladekarl, MD, DMSc.,Dept. of Oncology, Århus University Hospital, Denmark

Investigators

Principal Investigator:

Ulrik Lassen, MD., PH.D.

Rigshospitalet, Dept. of Oncology

More Information

No publications provided

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

Keywords provided by Rigshospitalet, Denmark:

Cholangiocarcinoma

Additional relevant MeSH terms:

Gallbladder Diseases
Molecular Mechanisms of Pharmacological Action
Gastrointestinal Diseases
Antineoplastic Agents
Physiological Effects of Drugs
Bevacizumab
Protein Kinase Inhibitors
Neoplasms by Site
Biliary Tract Diseases
Therapeutic Uses
Angiogenesis Modulating Agents
Growth Inhibitors
Erlotinib
Cholangiocarcinoma

Digestive System Neoplasms
Biliary Tract Neoplasms
Neoplasms by Histologic Type
Growth Substances
Enzyme Inhibitors
Angiogenesis Inhibitors
Pharmacologic Actions
Carcinoma
Neoplasms
Digestive System Diseases
Gastrointestinal Neoplasms
Gallbladder Neoplasms
Adenocarcinoma
Neoplasms, Glandular and Epithelial

ClinicalTrials.gov processed this record on November 30, 2009