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

NCT00531076 | Terminated Phase 1

• 3 other identifiers: VUMC 2006/194NL13724.029.06EudraCTnumber 2006-003149-17
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

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.

Conditions

Toxicity

Keywords

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

Outcome Measures

Primary Outcomes (1)

• 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

  1 year

Secondary Outcomes (1)

• 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

  1 year

Interventions

bevacizumab BIOLOGICAL

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

Also known as: Avastin

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Amsterdam UMC, location VUmc: lead

Study Sites (1)

VU University Medical Center

Amsterdam, 1007 MB, Netherlands

Location

MeSH Terms

Interventions

Bevacizumab

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Suresh Senan, MD, PhD

  Amsterdam UMC, location VUmc

  PRINCIPAL INVESTIGATOR

• Egbert F Smit, MD, PhD

  Amsterdam UMC, location VUmc

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: September 17, 2007
• First Posted: September 18, 2007
• Study Start: October 1, 2007
• Primary Completion: January 1, 2010
• Study Completion: January 1, 2010
• Last Updated: April 5, 2011

Record last verified: 2011-01

Locations

NL (1)