Primary objective: Efficacy of erlotinib plus bevacizumab subsequent to the combination of carboplatin, paclitaxel and bevacizumab as determined by the maximum achieved disease control rate (DCR, complete response, partial response, or stable…
ID
Source
Brief title
Condition
- Respiratory and mediastinal neoplasms malignant and unspecified
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Efficacy of erlotinib plus bevacizumab subsequent to the combination of
carboplatin, paclitaxel and bevacizumab as determined by the maximum achieved
disease control rate (complete response, partial response, or stable disease)
at 18 weeks
Secondary outcome
Efficacy of carboplatin, paclitaxel and bevacizumab as determined by PFS, DCR,
RR
Efficacy of bevacizumab and erlotinib as determined by DCR at 6, 12 and 27
weeks; PFS; RR
Overall survival
Safety profile of carboplatin, paclitaxel and bevacizumab and subsequent
bevacizumab and erlotinib
Determination of early response by FDG-PET
Background summary
Paclitaxel, carboplatin and bevacizumab demonstrated to be safe and effective
in advanced NSCLC patients. In studies bevacizumab has been continued until
progression. Preclinical data suggest rapid vascular re-growth in tumours after
reversal of VEGF inhibition. These preclinical findings support studying the
concept of continued use of VEGF inhibition in progressive patients. Further,
preclinical studies have shown that VEGF and EGFR inhibitors can have additive
effects and clinical trials have also produced promising data in second line
therapy combining the anti-VEGF monoclonal antibody bevacizumab with the
anti-EGFR antibody cetuximab or the EGFR tyrosine kinase inhibitor erlotinib.
The combination increases benefit compared with either of these anti-EGFR
agents alone. The toxicity profiles of bevacizumab and erlotinib are
non-overlapping and the combination is more favourable when compared to current
standard second line chemotherapy. In phase I, erlotinib 150mg/day p.o. plus
bevacizumab 15mg/kg i.v. every 21 days was established as the phase II dose,
although no true dose-limiting toxicities were observed. The most commonly
reported adverse events were rash, diarrhea, and proteinuria, which were never
more than mild to moderate.
Study objective
Primary objective:
Efficacy of erlotinib plus bevacizumab subsequent to the combination of
carboplatin, paclitaxel and bevacizumab as determined by the maximum achieved
disease control rate (DCR, complete response, partial response, or stable
disease) at 18 weeks
Secondary objectives:
Efficacy of carboplatin, paclitaxel and bevacizumab as determined by PFS, DCR,
RR
Efficacy of bevacizumab and erlotinib as determined by DCR at 6, 12 and 27
weeks; PFS; RR
Overall survival
Safety profile of carboplatin, paclitaxel and bevacizumab and subsequent
bevacizumab and erlotinib
Determination of early response by FDG-PET
Study design
Open-label phase II study
Intervention
4 cycles (or less in case of progression) with Paclitaxel, Carboplatin and
Bevacizumab. At (early) progression Bevacizumab 15 mg/kg i.v. q 21 days plus
Erlotinib 150 mg/day orally
Study burden and risks
The burden related to study procedures is limited as most procedures are
considered necessary in standard care. In the first three weeks in both the
first line as second line treatment the visits are more frequent (4 extra
visits including an venapunction) and radiological evaluation is more frequent
compared to standard care during bevacizumab-monotherapy and in the first 18
weeks of second line treatment (resulting in an estimated 3 extra CT-Thorax per
patient).
The favorable toxicity profile of the studied second line treatment compared to
standard second line treatment can be considered beneficial to the participant.
P.O. Box 9101
6500 HB Nijmegen
NL
P.O. Box 9101
6500 HB Nijmegen
NL
Listed location countries
Age
Inclusion criteria
- Advanced stage NSCLC (IIIB with malignant pleural effusion or stage IV) excluding squamous cell histology, with measurable or evaluable disease.
- No prior systemic therapy for advanced NSCLC, prior therapy for early stage disease with one regimen is acceptable if it was completed at least 6 months prior to study entry.
- Palliative radiotherapy to painful bony metastases will be permitted prior to study entry if completed prior to initiation of study treatment, and there are no residual sequelae of therapy such as bone marrow suppression.
- Life expectancy of at least 3 months.
- ECOG Performance status 0-1 (see appendix 2)
- Age 18 or higher.
-Female patients with reproductive potential must have a negative serum pregnancy test within 72 hours prior to start of study medication. All female patients of childbearing potential, and all male patients, must agree to use a medically acceptable method of contraception or agree to be abstinent throughout the treatment period and for 3 months after discontinuation of treatment
- Patients must have normal organ and marrow function
Exclusion criteria
- Prior systemic treatment for advanced NSCLC. One prior regimen (up to 4 cycles) of neoadjuvant or adjuvant therapy for early stage disease will be allowed if completed at least 6 months prior to study entry.
- Known brain metastases (in case of clinical signs or symptoms of brain metastases radiological evaluation is mandatory).
- Prior treatment with bevacizumab or erlotinib.
- History of allergic reactions or sensitivity attributed to compounds of similar chemical or biologic composition to bevacizumab or erlotinib.
- Current, recent (within 4 weeks of the first infusion of this study), or planned participation in any other experimental drug study.
- Concomitant chemotherapy, radiotherapy or investigational agents.
- Evidence of bleeding diathesis or coagulopathy.
- Use of full dose anti-coagulant agents.
- Pregnant (positive pregnancy test) or lactating women.
- Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to start, anticipation of need for major surgical procedure during the course of the study.
- Minor surgical procedures, fine needle aspirations or core biopsies within 7 days prior to start.
- History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to start.
- Serious, non-healing wound, ulcer, or bone fracture.
- Lung carcinoma of squamous cell histology or any histology in close proximity to a major vessel, or with significant cavitation as assessed by treating investigator in consultation with an attending radiologist.
- History of hemoptysis (bright red blood of 2.5 ml or more).
- Significant co-morbidities including:
- No uncontrolled hypertension (systolic > 150 mmHg and/or diastolic > 100 mmHg)
- Unstable angina
- New York Heart Association (NYHA) Grade II or greater congestive heart failure
- History of myocardial infarction within 6 months
- History of stroke within 6 months
- Clinically significant peripheral vascular disease
- Patients diagnosed with a tracheo-oesophagal fistula
- Another active malignancy except for non-melanoma skin cancers in the last 5 years.
- Inability to comply with study and/or follow-up procedures.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2007-005523-15-NL |
| CCMO | NL19600.091.08 |