Safety Study of Bevacizumab (Avastin) With Thoracic Radiation in Non-small Cell Cell Lung Cancer

April 4, 2011 updated by: Amsterdam UMC, location VUmc

Phase I Study of Concurrent Bevacizumab (Avastin) With Involved-field Thoracic Radiotherapy for Inoperable Non-squamous Non-small Cell Lung Cancer, Followed by Both Concurrent and Maintenance Bevacizumab

In spite of the use of radiation combined with conventional chemotherapy, the long-term survival prognosis for most patients with locally advanced non-small cell lung cancer is disappointing. Much effort is currently focussed on exploring new molecular targeted agents that may improve upon survival. The addition of an agent that targets blood vessel formation in tumors, bevacizumab or Avastin, to conventional chemotherapy has been shown to improve survival in metastatic non-small cell lung cancer. Data from animal studies have shown that bevacizumab and related agents also increase tumor cure rates when administered both during and after radiotherapy. This suggests that combined bevacizumab and chemo-radiation may improve survival in local-advanced disease as well. Before such clinical studies can commence, the safety and normal tissue toxicity profile of bevacizumab with thoracic radiotherapy must first be established. In this study, escalating doses of bevacizumab will be administered during radiotherapy, followed by maintenance bevacizumab.

Study Overview

Status

Terminated

Conditions

Toxicity

Intervention / Treatment

Biological: bevacizumab

Study Type

Interventional

Enrollment (Actual)

Phase

Phase 1

Contacts and Locations

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

Study Locations

Netherlands
- - Amsterdam, Netherlands, 1007 MB
    - VU University Medical Center

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.

Eligibility Criteria

Ages Eligible for Study

Child
Adult
Older Adult

Accepts Healthy Volunteers

Genders Eligible for Study

All

Description

Inclusion criteria:

Cytologically or histologically confirmed stages II or III non-squamous NSCLC
No evidence of tumour invading major blood vessels and no active hemoptysis (bright red blood of at least ½ teaspoon) in the 28 days prior to randomization.
No prior systemic therapy for NSCLC. Prior surgery and/or extra-thoracic irradiation is permitted.
Presence of at least one measurable target lesion
Age 18 or greater.
WHO performance status of 0 or 1.
Acceptable pulmonary function as defined by a Fev1 of ≥30% and a DLCO of ≥40% of predicted
Life expectancy of at least 12 weeks.
Adequate hematological, renal and hepatic functions
- Absolute neutrophil count >2x109/l.
- Platelet count > 100x109/l.
- Total bilirubin < 1.5 x UNL
- ASAT/ALAT < 2 x UNL
- Alkaline phosphatase < 5 x UNL
- Creatinine < 130 μmol/L
- Creatinine clearance > 60 ml/min; measured or calculated
Urine dipstick for proteinuria < 1+. If urine dipstick is ≥ 1, 24 hour urine must demonstrate < 500 mg of protein in 24 hours.
No pre-existing sensory neurotoxicity grade 2 (CTC)
No active (uncontrolled) infection requiring antibiotics

Exclusion criteria:

Mixed tumor types with small cell lung cancer or squamous cell carcinoma
Other serious diseases, such as heart failure, angina pectoris, myocardial infarction within the last 6 months, uncontrolled hypertension
Serious non-healing wound or ulcer.
ASAT and ALAT > 1,5 x UNL
alkaline phosphatase 5 x UNL
Evidence of bleeding diathesis or coagulopathy.
Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be assessed with the patient before registration in the trial.
Participation in other trial with investigational drug or treatment modality.

Study Plan

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

How is the study designed?

Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Interventional Model: Single Group Assignment
Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
To establish the safety and tolerability of 2 dose-levels of bevacizumab administered every 3 weeks with concurrent thoracic radiotherapy to 66 Gy,and also maintenance (15 mg/kg) bevacizumab following completion of thoracic radiotherapy Time Frame: 1 year	1 year

Secondary Outcome Measures

Outcome Measure	Time Frame
Correlate all observed toxicity with dose-volume histograms of irradiated normal organs and explore surrogate tumor end-points that may correlate with the efficacy of combined treatment with anti-VEGF targeted therapy Time Frame: 1 year	1 year

Collaborators and Investigators

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

Sponsor

Amsterdam UMC, location VUmc

Investigators

Principal Investigator: Egbert F Smit, MD, PhD, Amsterdam UMC, location VUmc
Principal Investigator: Suresh Senan, MD, PhD, Amsterdam UMC, location VUmc

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 Major Dates

Study Start

October 1, 2007

Primary Completion (Actual)

January 1, 2010

Study Completion (Actual)

January 1, 2010

Study Registration Dates

First Submitted

September 17, 2007

First Submitted That Met QC Criteria