Chemotherapy Plus Bevacizumab in Elderly Non-small Cell Lung Cancer Patients

Study Overview
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Brief Summary
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A phase II Study of an adapted chemotherapy regimen plus bevacizumab in elderly non-small cell lung cancer patients selected by geriatric assessment

Detailed Description
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CRITERIOS INCLUSION Written informed consent confirming that the patient understands the study objective and the procedures required. Patients must be able to accomplish with the study protocol. Men and women ≥70 years old. Histologically or cytologically confirmed diagnosis of non-squamous non-small cell lung cancer (NSCLC) with EGFR gen mutational status negative or non-determinable. Patients with stage IV disease. Patients who have not received first-line treatment Patients with ECOG performance status 0 or 1. Adequate bone marrow function, defined as: Absolute neutrophil count (ANC) ≥1.500/mm3 or ≥1.5x109/L; Hemoglobin ≥ 9 g/dL. Platelet count ≥ 100.000/mm3. Adequate renal function, defined as: Creatinine clearance ≥ 40 ml/min, according to MDRD formula. Urine dipstick proteinuria <2+. If urine dipstick for proteinuria ≥2+ 24 hours urine must be collected within 24 hours, and proteins must be less than 1 g. Fertile males must use an effective contraceptive method (error rate per year <1%) during the trial and until 6 months after the last study treatment dose, such as sexual abstinence, previous vasectomy and/or having a partner using any of following methods: implantables, injections, combined oral contraceptives and/or intrauterine device (hormonal only). CRITERIOS EXCLUSION Previous chemotherapy for advanced NSCLC. History of haemoptysis grade ≥ 2 (defined as at least 2.5 mL of bright red blood) in the 3 months before inclusion. Major surgery (including open biopsy), significant traumatic injuries in the 28 days before inclusion or anticipation of the need of major surgical procedure during the treatment period Minor surgery, including permanent catheter insertion, in the 24 hours before bevacizumab infusion. Untreated brain metastases. Patients with CNS metastases treated with radiotherapy or surgery may be included if there is no evidence of progression after treatment Radiological evidence of a tumor that invades or is adjacent to a main blood vessel (e.g. lung artery or superior cava venous). Radiotherapy, in any lesion and for any reason, within 28 days before inclusion. Palliative radiotherapy for bone lesions within 14 days before inclusion is allowed. Treatment with aspirin (>325 mg/day) or clopidogrel (>75 mg/day) within 10 days prior to bevacizumab first dose. Use of full dose of oral or parenteral anticoagulants or thrombolytic agents in therapeutic doses. Prophylactic use of anticoagulant therapy is allowed. Uncontrolled hypertension (systolic BP >140 mmHg, diastolic BP >90mmHg) in the 28 days previous to inclusion or history of hypertensive crisis, or hypertensive encephalopathy. Clinically significant cardiovascular disease (i.e. cerebrovascular accident (CVA), myocardial infarction within 6 months prior to inclusion, unstable angina, congestive cardiac insufficiency NYHA ≥ II, left ventricular ejection fraction (LVEF) <50% or serious cardiac arrhytmia), not responding to treatment or that can interfere with trial treatment administration. Not healed wounds, active peptic ulcer or untreated bone fracture. Hypersensibility to any of the active ingredients of the study treatment (bevacizumab, carboplatine and paclitaxel) or any of its excipients. Serious cognitive impairment that limits the patient to understand and answer the study questionnaires. Inability to comply with the study protocol and/or follow-up procedures due to psychological, familiar, social or geographical problems Patients with an ADL score <5 at the screening. Patients with dementia: 9-12 points in the Folstein MMS at the screening. Patients accomplishing fragility Balducci criteria at the screening: Age ≥ 85 years old Dependence in 1 or more ADL >3 comorbilities >1 geriatric syndrome OBJETIVOS To assess the toxicity of the treatment in elderly patients (≥70 years) with NSC lung cancer who meet inclusion criteria for bevacizumab and selected based on a geriatric evaluation. Determine predictive factors of toxicity in the elderly population (≥70 years). Determine objective response rate Determine disease control rate Determine progression free survival Determine overall survival Determine safety of the treatment combination VARIABLES Primary endpoint: Rate of grade 3-4 neutropenia defined according to National Cancer Institute Common Terminology Criteria version 4.0 (NCI-CTC v4.0). Secondary endpoints: Items of the Comprehensive Geriatric Assessment (CGA) scale as predictive factors for toxicity end-points. Objective response according to the Response Evaluation Criteria In Solid Tumors (RECIST v1.1). Progression-free survival. Overall survival.

Official Title
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Phase II Trial of Geriatric Evaluation as Selection Criteria and Predictive Factor of Safety in Elderly Patients (≥ 70 Years) With Non-small Cell Lung Cancer (NSCLC)That Can be Treated With Bevacizumab, Carboplatin and Paclitaxel

Conditions
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Non-small Cell Lung Cancer (NSCLC)

Intervention / Treatment
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* Biological: bevacizumab, carboplatin and paclitaxel


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Written informed consent confirming that the patient understands the study objective and the procedures required. Patients must be able to accomplish with the study protocol. Men and women ≥70 years old. Histologically or cytologically confirmed diagnosis of non-squamous non-small cell lung cancer (NSCLC) with EGFR gen mutational status negative or non-determinable. Patients with stage IV disease. Patients who have not received first-line treatment Patients with ECOG performance status 0 or 1. Adequate bone marrow function, defined as: Absolute neutrophil count (ANC) ≥1.500/mm3 or ≥1.5x109/L; Hemoglobin ≥ 9 g/dL. Platelet count ≥ 100.000/mm3. • Adequate renal function, defined as: Creatinine clearance ≥ 40 ml/min, according to MDRD formula. Urine dipstick proteinuria <2+. If urine dipstick for proteinuria ≥2+ 24 hours urine must be collected within 24 hours, and proteins must be less than 1 g. • Fertile males must use an effective contraceptive method (error rate per year <1%) during the trial and until 6 months after the last study treatment dose, such as sexual abstinence, previous vasectomy and/or having a partner using any of following methods: implantables, injections, combined oral contraceptives and/or intrauterine device (hormonal only). Exclusion Criteria: Previous chemotherapy for advanced NSCLC. History of haemoptysis grade ≥ 2 (defined as at least 2.5 mL of bright red blood) in the 3 months before inclusion. Major surgery (including open biopsy), significant traumatic injuries in the 28 days before inclusion or anticipation of the need of major surgical procedure during the treatment period Minor surgery, including permanent catheter insertion, in the 24 hours before bevacizumab infusion. Untreated brain metastases. Patients with CNS metastases treated with radiotherapy or surgery may be included if there is no evidence of progression after treatment Radiological evidence of a tumor that invades or is adjacent to a main blood vessel (e.g. lung artery or superior cava venous). Radiotherapy, in any lesion and for any reason, within 28 days before inclusion. Palliative radiotherapy for bone lesions within 14 days before inclusion is allowed. Treatment with aspirin (>325 mg/day) or clopidogrel (>75 mg/day) within 10 days prior to bevacizumab first dose. Use of full dose of oral or parenteral anticoagulants or thrombolytic agents in therapeutic doses. Prophylactic use of anticoagulant therapy is allowed. Uncontrolled hypertension (systolic BP >140 mmHg, diastolic BP >90mmHg) in the 28 days previous to inclusion or history of hypertensive crisis , or hypertensive encephalopathy. Clinically significant cardiovascular disease (i.e. cerebrovascular accident (CVA), myocardial infarction within 6 months prior to inclusion, unstable angina, congestive cardiac insufficiency NYHA ≥ II, left ventricular ejection fraction (LVEF) <50% or serious cardiac arrhythmia), not responding to treatment or that can interfere with trial treatment administration. Not healed wounds, active peptic ulcer or untreated bone fracture. Hypersensibility to any of the active ingredients of the study treatment (bevacizumab, carboplatine and paclitaxel) or any of its excipients. Serious cognitive impairment that limits the patient to understand and answer the study questionnaires. Inability to comply with the study protocol and/or follow-up procedures due to psychological, familiar, social or geographical problems Patients with an ADL score <5 at the screening. Patients with dementia: 9-12 points in the Folstein MMS at the screening. Patients accomplishing fragility Balducci criteria at the screening: Age ≥ 85 years old Dependence in 1 or more ADL >3 comorbidities >1 geriatric syndrome

Ages Eligible for Study
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Minimum Age: 70 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Intervention Model: Single Group Assignment
Interventional Model Description: Chemotherapy Regimen Plus Bevacizumab
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: bevacizumab, carboplatin and paclitaxel<br>bevacizumab, carboplatin and paclitaxel | Biological: bevacizumab, carboplatin and paclitaxel<br>* 4-6 initial cycles of bevacizumab, carboplatin and paclitaxel bevacizumab until progression or toxicity<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of grade 3-4 neutropenia defined according to National Cancer Institute Common Terminology Criteria version 4.0 (NCI-CTC v4.0) |  | participants will be followed for the duration of the study, around 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma VEGF |  | participants will be followed for the duration of the study, around 3 years | 
| Objective response and Stable disease according to RECIST |  | participants will be followed for the duration of the study, around 3 years | 
| progression-free survival and overall survival |  | participants will be followed for the duration of the study, around 3 years |