Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

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

This study has been terminated.
(Study terminated due to toxicity)
Sponsor:
Information provided by:
VU University Medical Center
ClinicalTrials.gov Identifier:
NCT00531076
First received: September 17, 2007
Last updated: April 4, 2011
Last verified: January 2011
  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 1

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


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 ]

Enrollment: 6
Study Start Date: October 2007
Study Completion Date: January 2010
Primary Completion Date: January 2010 (Final data collection date for primary outcome measure)
Intervention Details:
    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

    Other Name: Avastin
  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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

Locations
Netherlands
VU University Medical Center
Amsterdam, Netherlands, 1007 MB
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: Professor Suresh Senan, VU Medical Center
ClinicalTrials.gov Identifier: NCT00531076     History of Changes
Other Study ID Numbers: VUMC 2006/194, NL13724.029.06, EudraCTnumber 2006-003149-17
Study First Received: September 17, 2007
Last Updated: April 4, 2011
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:
Carcinoma, Non-Small-Cell Lung
Lung Neoplasms
Bronchial Neoplasms
Carcinoma, Bronchogenic
Lung Diseases
Neoplasms
Neoplasms by Site
Respiratory Tract Diseases
Respiratory Tract Neoplasms
Thoracic Neoplasms
Bevacizumab
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Antineoplastic Agents
Growth Inhibitors
Growth Substances
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on November 20, 2014