Bevacizumab (Avastin®) + Erlotinib as First-line Therapy for Stage IIIB/IV or Recurrent, Non-squamous Cell Lung Cancer
|Study Design:||Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||AVF4236s: Bevacizumab (Avastin®) + Erlotinib as First-line Therapy for Stage IIIB/IV or Recurrent, Non-squamous Cell Lung Cancer|
- Evaluation of Overall Survival [ Time Frame: 2 years ] [ Designated as safety issue: No ]The length of time from the start of treatment for a disease that patients are still alive.
- Evaluation of Progression-free Survival [ Time Frame: 2 years ] [ Designated as safety issue: No ]The length of time during and after bevacizumab-erlotinib that a patient lives with the disease but does not progress according to RECIST 1.0 Criteria. Per Response Evaluation Criteria In Solid Tumors (RECIST v1.0) for target lesions and assessed by CT: Progressive Disease (PD), >=20% increase in the sum of the longest diameter of target lesions
- Evaluation of Response Rate [ Time Frame: 2 years ] [ Designated as safety issue: No ]The percentage of patients in which response (CR + PR) was observed: Per Response Evaluation Criteria In Solid Tumors (RECIST v1.0) for target lesions and assessed by CT: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions
|Study Start Date:||August 2007|
|Study Completion Date:||May 2013|
|Primary Completion Date:||May 2013 (Final data collection date for primary outcome measure)|
Drug: Bevacizumab and Erlotinib
Erlotinib 150 mg/day orally plus bevacizumab 15 mg/kg intravenously every 21 days
The combination of Bevacizumab and Erlotinib show encouraging activity for patients with previously treated, non-small-cell lung cancer. In a phase I/II study of erlotinib and bevacizumab in patients with nonsquamous stage IIIB/IV NSCLC with one or more prior chemotherapy exposures, a recommended phase II dose was established at erlotinib 150 mg/day orally plus bevacizumab 15 mg/kg intravenously every 21 days (13) Forty patients were treated at the recommended Phase II dose. The median age was 59 years (range, 36 to 72 years), 21 were female, 30 had adenocarcinoma histology, nine were never-smokers, and 22 had > or = two prior regimens (three patients had > or = four prior regimens). The most common adverse events were mild to moderate rash, diarrhea, and proteinuria. No pharmacokinetic interactions were identified. Eight patients (20.0%; 95% CI, 7.6% to 32.4%) had partial responses and 26 (65.0%; 95% CI, 50.2% to 79.8%) had stable disease as their best response. The median overall survival for the 34 patients treated at the phase II dose was 12.6 months, with progression-free survival of 6.2 months. These data compare favorably with conventional chemotherapy in the salvage setting for NCSLC where the response rates are < 10% and median survivals are 6-8 months (14-16).
In an attempt to improve the therapeutic index for initial therapy of metastatic NSCLC, the combination of bevacizumab and erlotinib is being proposed as first-line treatment in place of conventional chemotherapy. The regimen will be beneficial if toxicity is reduced and efficacy is unchanged or if efficacy is improved. Since this regimen causes no hair loss, minimal nausea and no cytopenia, which nearly eliminated the risks of infections and bleeding, the combination of targeted agents appears to be better tolerated than conventional chemotherapy. Efficacy may also be improved since its activity in the salvage setting when patients are less likely to respond to any treatment rivals that of conventional chemotherapy in the untreated setting. In addition, erlotinib alone in the untreated setting can yield results that are not dissimilar from chemotherapy under similar conditions. Hence, it is hypothesized that the combination of erlotinib plus bevacizumab can produce superior results with less toxicity. This trial is intended to provide pilot data for a future randomized trial of this combination of targeted agents versus conventional chemotherapy for advanced NSCLC.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00585377
|United States, Utah|
|University of Utah|
|Salt Lake City, Utah, United States, 84112|
|Principal Investigator:||Wallace Akerley, MD||University of Utah|