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AVF4236s: Bevacizumab (Avastin®) + Erlotinib as First-line Therapy for Stage IIIB/IV or Recurrent, Non-squamous Cell Lung Cancer

Phase 2
18 Years
Open (Enrolling)

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Trial Information

AVF4236s: Bevacizumab (Avastin®) + Erlotinib as First-line Therapy for Stage IIIB/IV or Recurrent, Non-squamous Cell Lung Cancer

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.

Inclusion Criteria

Inclusion Criteria

- Histological or cytological diagnosis of non-squamous, non-small cell lung cancer.
Mixed tumors will be categorized by the predominant cell type unless small cell
elements are present, in which case the patient is ineligible.

- Stage wet IIIB-IV or recurrent disease

- No significant hemoptysis (bright red blood< 1/2 teaspoon or more per episode within
3 months)

- Performance status of 0-1

- Prior radiation allowed if > 15 days.

- No prior treatment for metastatic disease. Adjuvant treatment allowed if greater
than 6 months has passed.

Exclusion Criteria

Disease-Specific Exclusions

- History of hemoptysis (bright red blood of 1/2 teaspoon or more per episode) within 3
months prior to study enrollment.

- Current, ongoing treatment with full-dose warfarin

- Current or recent (within 10 days of enrollment) use of aspirin (>325 mg/day) or
chronic use of other NSAIDs.

- Performance status =2-4

- Known HIV-related disease

General Medical Exclusions

Subjects meeting any of the following criteria are ineligible for study entry:

- Inability to comply with study and/or follow-up procedures

- Current, recent (within 4 weeks of the first infusion of this study), or planned
participation in an experimental drug study other than a Genentech-sponsored
bevacizumab cancer study

Bevacizumab (Avastin®)-Specific Exclusions

- Inadequately controlled hypertension (defined as systolic blood pressure >150 and/or
diastolic blood pressure > 100 mmHg on antihypertensive medications)

- Any prior history of hypertensive crisis or hypertensive encephalopathy

- New York Heart Association (NYHA) Grade II or greater congestive heart failure (see
Appendix E)

- History of myocardial infarction or unstable angina within 6 months prior to study

- History of stroke or transient ischemic attack within 6 months prior to study

- Significant vascular disease (e.g., aortic aneurysm, aortic dissection)

- Symptomatic peripheral vascular disease

- Evidence of bleeding diathesis or coagulopathy

- Major surgical procedure, open biopsy, or significant traumatic injury within 28 days
prior to study enrollment or anticipation of need for major surgical procedure during
the course of the study

- Core biopsy or other minor surgical procedure, excluding placement of a vascular
access device, within 7 days prior to study enrollment

- History of abdominal fistula, gastrointestinal perforation, or intra-abdominal
abscess within 6 months prior to study enrollment

- Serious, non-healing wound, ulcer, or bone fracture

- Proteinuria at screening as demonstrated by either

- Urine protein:creatinine (UPC) ratio > 1.0 at screening OR

- Urine dipstick for proteinuria ≥ 2+ (patients discovered to have ≥2+ proteinuria on
dipstick urinalysis at baseline should undergo a 24 hour urine collection and must
demonstrate ≤ 1g of protein in 24 hours to be eligible).

- Known hypersensitivity to any component of bevacizumab

- Pregnant (positive pregnancy test) or lactating. Use of effective means of
contraception (men and women) in subjects of child-bearing potential

Type of Study:


Study Design:

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Overall survival

Outcome Time Frame:

Aug 2007-Aug 2007

Safety Issue:


Principal Investigator

Wallace Akerley, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

University of Utah


United States: Institutional Review Board

Study ID:




Start Date:

August 2007

Completion Date:

December 2013

Related Keywords:

  • Cancer
  • Lung Neoplasms



University of Utah Salt Lake City, Utah