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

Primary Purpose

Toxicity

Status

Terminated

Phase

Phase 1

Locations

Netherlands

Study Type

Interventional

Intervention

bevacizumab

About this trial

This is an interventional treatment trial for Toxicity focused on measuring bevacizumab, thoracic radiotherapy, locally-advanced non-small cell lung cancer

Eligibility Criteria

undefined - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

VU University Medical Center

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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

Full Information

NCT ID

NCT00531076

First Posted

September 17, 2007

Last Updated

April 4, 2011

Sponsor

Amsterdam UMC, location VUmc

1. Study Identification

Unique Protocol Identification Number

NCT00531076

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

January 2011

Overall Recruitment Status

Terminated

Why Stopped

Study terminated due to toxicity

Study Start Date

October 2007 (undefined)

Primary Completion Date

January 2010 (Actual)

Study Completion Date

January 2010 (Actual)

3. Sponsor/Collaborators

Name of the Sponsor

Amsterdam UMC, location VUmc

4. Oversight

Data Monitoring Committee

5. Study Description

Brief Summary

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Toxicity

Keywords

bevacizumab, thoracic radiotherapy, locally-advanced non-small cell lung cancer

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

6 (Actual)

8. Arms, Groups, and Interventions

Intervention Type

Biological

Intervention Name(s)

bevacizumab

Other Intervention Name(s)

Avastin

Intervention Description

Intravenous bevacizumab at 7.5mg/kg and 15mg/kg concurrently with thoracic radiotherapy in sequential cohorts. In the final dose level, bevacizumab 15mg/kg concurrent with radiation will be followed by maintenance bevacizumab 15mg/kg up to a maximum of 6 cycles

Primary Outcome Measure Information:

Title

Time Frame

1 year

Secondary Outcome Measure Information:

Title

Time Frame

1 year

10. Eligibility

Sex

All

Accepts Healthy Volunteers

Eligibility Criteria

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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Suresh Senan, MD, PhD

Organizational Affiliation

Amsterdam UMC, location VUmc

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Egbert F Smit, MD, PhD

Organizational Affiliation

Amsterdam UMC, location VUmc

Official's Role

Principal Investigator

Facility Information:

Facility Name

VU University Medical Center

City

Amsterdam

ZIP/Postal Code

1007 MB

Country

Netherlands

12. IPD Sharing Statement

Learn more about this trial

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

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