Safety Study of Bevacizumab (Avastin) With Thoracic Radiation in Non-Small Cell Cell Lung Cancer - Full Text View

Sponsor:	VU University Medical Center
Information provided by:	VU University Medical Center
ClinicalTrials.gov Identifier:	NCT00531076

Purpose

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.

Condition	Intervention	Phase
Toxicity	Biological: bevacizumab	Phase I

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

Resource links provided by NLM:

MedlinePlus related topics: Cancer Lung Cancer

Drug Information available for: Bevacizumab

U.S. FDA Resources

Further study details as provided by VU University Medical Center:

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 [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]

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 [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	20
Study Start Date:	January 2007
Estimated Study Completion Date:	June 2009
Estimated Primary Completion Date:	December 2008 (Final data collection date for primary outcome measure)

Intervention Details:

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

Eligibility

Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00531076

Contacts

Contact: Suresh Senan, MD, PhD

31-20-444-0405

s.senan@vumc.nl

Locations

Netherlands
VU University Medical Center	Recruiting
Amsterdam, Netherlands, 1007 MB
Principal Investigator: Suresh Senan, MD, PhD

Sponsors and Collaborators

VU University Medical Center

Investigators

Principal Investigator:	Suresh Senan, MD, PhD	VU University Medical Center
Principal Investigator:	Egbert F Smit, MD, PhD	VU University Medical Center

More Information

No publications provided

Responsible Party:	VU Medical Center ( Professor Suresh Senan )
Study ID Numbers:	VUMC 2006/194, NL13724.029.06, EudraCTnumber 2006-003149-17
Study First Received:	September 17, 2007
Last Updated:	April 22, 2008
ClinicalTrials.gov Identifier:	NCT00531076 History of Changes
Health Authority:	Netherlands: Medical Ethics Review Committee (METC)

Keywords provided by VU University Medical Center:

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

Additional relevant MeSH terms:

Thoracic Neoplasms
Respiratory Tract Neoplasms
Neoplasms by Histologic Type
Antineoplastic Agents
Growth Substances
Physiological Effects of Drugs
Bevacizumab
Angiogenesis Inhibitors
Pharmacologic Actions
Carcinoma

Neoplasms
Neoplasms by Site
Respiratory Tract Diseases
Lung Neoplasms
Therapeutic Uses
Lung Diseases
Growth Inhibitors
Angiogenesis Modulating Agents
Carcinoma, Non-Small-Cell Lung
Neoplasms, Glandular and Epithelial

ClinicalTrials.gov processed this record on November 09, 2009