Non-squamous Non-small Cell Lung Cancer
Conditions
Keywords
lung cancer, NSCLC, elderly, non-squamous, Elderly patients at least 65 years old, first line therapy, non-squamous non-small cell lung cancer stage IIIb or IV
Brief summary
Multi-center, open, randomized (parallel) and comparative phase III. Eligible patients will receive bevacizumab + chemotherapy for a minimum of 4 cycles followed by bevacizumab (+ pemetrexed, if appropriate) maintenance therapy until disease progression. Arm A: Bevacizumab + pemetrexed Arm B: Bevacizumab + pemetrexed + carboplatin
Detailed description
Primary: * Proof of non-inferior efficacy of a monochemotherapy regimen of pemetrexed plus bevacizumab versus a combination chemotherapy regimen of pemetrexed-carboplatin plus bevacizumab in elderly patients(\> 65 years) as first-line treatment of advanced metastatic or recurrent non-squamous NSCLC by progression free survival Secondary: * To assess the efficacy of bevacizumab as measured by overall response rate and overall survival. * To assess the safety of bevacizumab in combination with pemetrexed and pemetrexed and carboplatin. * To assess quality of life by EORTC questionnaire QLQ-C30 and its lung cancer module LC-13 * To assess activity of daily life (iADL) in relation to ECOG performance status prior to study treatment * To assess patient's outcome and treatment delivery in relation to the Charlson comorbidity score and the Simplified Comorbidity Score
Interventions
DRUGBevacizumab + Pemetrexed
Bevacizumab 7,5 mg/kg i.v. over 60 min every 3 weeks plus pemetrexed 500 mg/m2 i.v. on D1 over 10 minutes every 3 weeks
DRUGBevacizumab + Pemetrexed + Carboplatin
Bevacizumab 7,5 mg/kg i.v. over 60 min every 3 weeks plus pemetrexed 500 mg/m2 i.v. on D1 over 10 minutes and carboplatin AUC 5 on D1 every 3 weeks
Sponsors
Roche Pharma AG
Eli Lilly and Company
PD Dr. med. Wolfgang Schuette
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
65 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Stage IIIb and IV NSCLC, excluded squamous cell NSCLC * Age ≥ 65 years * ECOG 0-2
Exclusion criteria
* Mixed, non-small cell and small cell tumours or mixed adenosquamous carcinomas with a predominant squamous component * History of haemoptysis * Evidence of tumour invading major blood vessels on imaging * Radiotherapy within 28 days prior to enrolment * Patients who are unable to interrupt aspirin or other nonsteroidal anti-inflammatory agents, other than an aspirin dose ≤ 1.3 grams per day, for a 5-day period (8-day period for long-acting agents, such as piroxicam) * Current or recent (within 10 days of first dose of bevacizumab) use of full-dose oral or parenteral anticoagulants or thrombolytic agent for therapeutic purposes. Prophylactic use of anticoagulants is allowed * Clinically significant (i.e. active) cardiovascular disease for example CVA (≤6 months before enrolment), myocardial infarction (≤6 months before enrolment), unstable angina, CHF NYHA Class ≥II, serious cardiac arrhythmia requiring medication during the study and might interfere with regularity of the study treatment, or not controlled by medication * Non-healing wound, active peptic ulcer or bone fracture * History of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess within 6 months of enrolment
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival | 42 months | Progression free survival (defined as the number of days from the day of the first treatment until day of death (from any cause) or progression, whichever occurs earlier, or until the day of the last response assessment, if no progression or death (from any cause) is observed during the study). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival | 42 months | Overall survival (defined as the number of days from the day of first treatment to death (from any cause), or until the last day if we know that the patient is alive). |
Countries
Germany
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Bevacizumab + Pemetrexed Bevacizumab + Pemetrexed
Bevacizumab + Pemetrexed: Bevacizumab 7,5 mg/kg i.v. over 60 min every 3 weeks plus pemetrexed 500 mg/m2 i.v. on D1 over 10 minutes every 3 weeks | 119 |
| Bevacizumab + Pemetrexed + Carboplatin Bevacizumab + Pemetrexed + Carboplatin
Bevacizumab + Pemetrexed + Carboplatin: Bevacizumab 7,5 mg/kg i.v. over 60 min every 3 weeks plus pemetrexed 500 mg/m2 i.v. on D1 over 10 minutes and carboplatin AUC 5 on D1 every 3 weeks | 134 |
| Total | 253 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 17 | 22 |
| Overall Study | Death | 7 | 9 |
| Overall Study | Lack of Efficacy | 5 | 2 |
| Overall Study | screening failure, unknown | 11 | 4 |
| Overall Study | Withdrawal by Subject | 3 | 1 |
Baseline characteristics
| Characteristic | Bevacizumab + Pemetrexed | Bevacizumab + Pemetrexed + Carboplatin | Total |
|---|---|---|---|
| Age, Continuous | 71.0 years | 72.0 years | 71.5 years |
| Sex: Female, Male Female | 45 Participants | 48 Participants | 93 Participants |
| Sex: Female, Male Male | 74 Participants | 86 Participants | 160 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 61 / 119 | 97 / 134 |
| serious Total, serious adverse events | 8 / 119 | 7 / 134 |
Outcome results
Primary
Progression Free Survival
Progression free survival (defined as the number of days from the day of the first treatment until day of death (from any cause) or progression, whichever occurs earlier, or until the day of the last response assessment, if no progression or death (from any cause) is observed during the study).
Time frame: 42 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Bevacizumab + Pemetrexed | Progression Free Survival | 4.8 months |
| Bevacizumab + Pemetrexed + Carboplatin | Progression Free Survival | 6.8 months |
p-value: 0.058395% CI: [0.989, 1.682]Wilcoxon (Mann-Whitney)
Secondary
Overall Survival
Overall survival (defined as the number of days from the day of first treatment to death (from any cause), or until the last day if we know that the patient is alive).
Time frame: 42 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Bevacizumab + Pemetrexed | Overall Survival | 11.6 months |
| Bevacizumab + Pemetrexed + Carboplatin | Overall Survival | 14.4 months |
p-value: 0.386995% CI: [0.794, 1.499]Wilcoxon (Mann-Whitney)