Clinical trial NCT01980472: Chemotherapy Plus Bevacizumab in Elderly Non-small Cell Lung Cancer Patients
Official title: 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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Non-small Cell Lung Cancer (NSCLC)
Lead sponsor: Grupo de Investigación y Divulgación Oncológica
Sponsor class: OTHER
First posted: 2013-11-11
Enrollment: 50
Sex: ALL
Minimum age (years): 70
Maximum age (years): 85
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Chemotherapy Regimen Plus Bevacizumab
Primary purpose: OTHER

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.

Eligibility criteria: 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

Primary outcomes:
measure: Rate of grade 3-4 neutropenia defined according to National Cancer Institute Common Terminology Criteria version 4.0 (NCI-CTC v4.0)
timeFrame: participants will be followed for the duration of the study, around 3 years
Secondary outcomes:
measure: Plasma VEGF
timeFrame: participants will be followed for the duration of the study, around 3 years
measure: Objective response and Stable disease according to RECIST
timeFrame: participants will be followed for the duration of the study, around 3 years
measure: progression-free survival and overall survival
timeFrame: participants will be followed for the duration of the study, around 3 years
Other outcomes:
Locations:
city: Alcoy
country: Spain
facility: Hospital Virgen de los Lirios
state: Comunidad Valenciana
city: Castellón
country: Spain
facility: Hospital de Castellón
state: Comunidad Valenciana
city: Elda
country: Spain
facility: Hospital de Elda
state: Comunidad Valenciana
city: Manises
country: Spain
facility: Hospital de Manises
state: Comunidad Valenciana
city: Sagunto
country: Spain
facility: Hospital de Sagunto
state: Comunidad Valenciana
city: San Juan
country: Spain
facility: Hospital San Juan
state: Comunidad Valenciana
city: Valencia
country: Spain
facility: Hospital U. y P. La Fe
state: Comunidad Valenciana
city: Xátiva
country: Spain
facility: Hospital Lluis Alcanyis
state: Comunidad Valenciana
city: Alicante
country: Spain
facility: Hospital General de Alicante
city: Valencia
country: Spain
facility: Hospital General de Valencia
Study officials:
affiliation: Grup d'investigació i divulgació en oncologia
name: Oscar Juan Vidal, Dr.
role: PRINCIPAL_INVESTIGATOR
References: