CancerPhase 2NCT00585377
Bevacizumab (Avastin®) + Erlotinib as First-line Therapy for Stage IIIB/IV or Recurrent, Non-squamous Cell Lung Cancer
A Phase 2 study testing Bevacizumab and Erlotinib in people with Cancer, run by University of Utah at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Cancer
- What is being tested?
- Bevacizumab and Erlotinib
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 1 siteUnited States
- Study dates
- Aug 2007to May 2013
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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
Show all 28Show fewer
- 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 enrollment
- History of stroke or transient ischemic attack within 6 months prior to study enrollment
- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: AVF4236s: Bevacizumab (Avastin®) + Erlotinib as First-line Therapy for Stage IIIB/IV or Recurrent, Non-squamous Cell Lung Cancer
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. 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.
Read the detailed description
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.
- Conditions
- Cancer
- Being tested
- Bevacizumab and Erlotinib
- Medical subject headings
- Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Bevacizumab and ErlotinibDrug
Also called Bevacizumab: Avastin®, Erlotinib: Tarceva®
Erlotinib 150 mg/day orally plus bevacizumab 15 mg/kg intravenously every 21 days
| Study group | Role | What they receive |
|---|---|---|
| 1 | Other | Not described Receives: Drug: Bevacizumab and Erlotinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Evaluation of Overall Survival
The length of time from the start of treatment for a disease that patients are still alive.
Measured: 2 years
Secondary outcomes (2)
Evaluation of Progression-free Survival
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
Measured: 2 years
Evaluation of Response Rate
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
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Jan 2008 (estimated)
- Study startAug 2007
- Primary completionMay 2013
- Study completionMay 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for CancerStudies of the same condition, open and under way.
- More trials run by University of UtahThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 50 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Utah
- Sponsor type
- University, hospital or other
- Collaborators
- Genentech, Inc.
- Responsible party
- Sponsor
- Investigators
- Wallace Akerley, MD, Principal investigator, University of Utah
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00585377
- Sponsor's protocol ID
- HCI24377
- Other IDs
- AVF4236s:
- Status last verified
- Aug 2015
- First submitted
- 21 Dec 2007
- Last updated
- 24 Sep 2015
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Akerley W, Boucher K, Rich N, Egbert L, Harker G, Bylund J, Van Duren T, Reddy C. A phase II study of bevacizumab and erlotinib as initial treatment for metastatic non-squamous, non-small cell lung cancer with serum proteomic evaluation. Lung Cancer. 2013 Mar;79(3):307-11. doi: 10.1016/j.lungcan.2012.12.005. Epub 2012 Dec 25.
PubMed 23273522
Study at a glance
From the registry record, last updated by the sponsor on 24 Sep 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- AVF4236s: Bevacizumab (Avastin®) + Erlotinib as First-line Therapy for Stage IIIB/IV or Recurrent, Non-squamous Cell Lung Cancer
- ClinicalTrials.gov ID
- NCT00585377
- Acronym / sponsor ID
- HCI24377
- Conditions
- Cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 50 participants (actual)
- Lead sponsor
- University of UtahUniversity, hospital or other
- Collaborators
- Genentech, Inc.
- Study start
- Aug 2007
- Primary completion
- May 2013 (actual)
- Study completion
- May 2013 (actual)
- First posted
- 3 Jan 2008 (estimated)
- Results
- Posted 24 Sep 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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. 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.
Detailed description
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 1 | Other | Drug: Bevacizumab and Erlotinib |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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.
Key exclusion criteria (28 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Bevacizumab and ErlotinibAlso: Bevacizumab: Avastin®, Erlotinib: Tarceva®Erlotinib 150 mg/day orally plus bevacizumab 15 mg/kg intravenously every 21 days | Drug | 1 |
Primary outcome
Evaluation of Overall Survival
Time frame: 2 years
The length of time from the start of treatment for a disease that patients are still alive.
2 secondary outcomes
Evaluation of Progression-free Survival
Time frame: 2 years
Evaluation of Response Rate
Time frame: 2 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Sep 2015.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 23273522Akerley W, Boucher K, Rich N, Egbert L, Harker G, Bylund J, Van Duren T, Reddy C. A phase II study of bevacizumab and erlotinib as initial treatment for metastatic non-squamous, non-small cell lung cancer with serum proteomic evaluation. Lung Cancer. 2013 Mar;79(3):307-11. doi: 10.1016/j.lungcan.2012.12.005. Epub 2012 Dec 25.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Wallace Akerley, MD principal investigator
University of Utah
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Bevacizumab and Erlotinib in people with Cancer, run by University of Utah at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 28 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 24 Sep 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 24 Sep 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Evaluation of Overall Survival (time frame: 2 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00585377, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Sep 2015.