Chemotherapy Plus Bevacizumab in Elderly Non-small Cell Lung Cancer Patients
- Conditions
- Non-small Cell Lung Cancer (NSCLC)
- Interventions
- Biological: bevacizumab, carboplatin and paclitaxel
- Registration Number
- NCT01980472
- Lead Sponsor
- Grupo de Investigación y Divulgación Oncológica
- Brief Summary
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
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.
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- All
- Target Recruitment
- 50
- 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).
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description bevacizumab, carboplatin and paclitaxel bevacizumab, carboplatin and paclitaxel bevacizumab, carboplatin and paclitaxel
- Primary Outcome Measures
Name Time Method 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
Name Time Method Plasma VEGF 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 Objective response and Stable disease according to RECIST participants will be followed for the duration of the study, around 3 years
Trial Locations
- Locations (10)
Hospital de Elda
🇪🇸Elda, Comunidad Valenciana, Spain
Hospital de Sagunto
🇪🇸Sagunto, Comunidad Valenciana, Spain
Hospital San Juan
🇪🇸San Juan, Comunidad Valenciana, Spain
Hospital Lluis Alcanyis
🇪🇸Xátiva, Comunidad Valenciana, Spain
Hospital de Manises
🇪🇸Manises, Comunidad Valenciana, Spain
Hospital Virgen de los Lirios
🇪🇸Alcoy, Comunidad Valenciana, Spain
Hospital General de Valencia
🇪🇸Valencia, Spain
Hospital General de Alicante
🇪🇸Alicante, Spain
Hospital de Castellón
🇪🇸Castellón, Comunidad Valenciana, Spain
Hospital U. y P. La Fe
🇪🇸Valencia, Comunidad Valenciana, Spain