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

Toxicity Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00531076
• Other study ID #: VUMC 2006/194
• Secondary ID: NL13724.029.06Eu
• Status: Terminated
• Phase: Phase 1
• First received: September 17, 2007
• Last updated: April 4, 2011
• Start date: October 2007
• Est. completion date: January 2010

Study information

• Verified date: January 2011
• Source: VU University Medical Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: Netherlands: Medical Ethics Review Committee (METC)
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 6
• Est. completion date: January 2010
• Est. primary completion date: January 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A and older

Eligibility

Inclusion criteria:

1. Cytologically or histologically confirmed stages II or III non-squamous NSCLC

2. 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.

3. No prior systemic therapy for NSCLC. Prior surgery and/or extra-thoracic irradiation is permitted.

4. Presence of at least one measurable target lesion

5. Age 18 or greater.

6. WHO performance status of 0 or 1.

7. Acceptable pulmonary function as defined by a Fev1 of =30% and a DLCO of =40% of predicted

8. Life expectancy of at least 12 weeks.

9. 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

10. Urine dipstick for proteinuria < 1+. If urine dipstick is = 1, 24 hour urine must demonstrate < 500 mg of protein in 24 hours.

11. No pre-existing sensory neurotoxicity grade 2 (CTC)

12. No active (uncontrolled) infection requiring antibiotics

Exclusion criteria:

1. Mixed tumor types with small cell lung cancer or squamous cell carcinoma

2. Other serious diseases, such as heart failure, angina pectoris, myocardial infarction within the last 6 months, uncontrolled hypertension

3. Serious non-healing wound or ulcer.

4. ASAT and ALAT > 1,5 x UNL

5. alkaline phosphatase 5 x UNL

6. Evidence of bleeding diathesis or coagulopathy.

7. 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.

8. Participation in other trial with investigational drug or treatment modality.

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Toxicity

Intervention

Biological:
• bevacizumab
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

Locations

Country	Name	City	State
Netherlands	VU University Medical Center	Amsterdam

Sponsors (1)

Lead Sponsor	Collaborator
VU University Medical Center

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Yes
Secondary	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	Yes