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

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

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

Study Overview

• Status: Unknown
• Conditions: Non-small Cell Lung Cancer (NSCLC)
• Intervention / Treatment: Biological: bevacizumab, carboplatin and paclitaxel

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.

• Study Type: Interventional
• Enrollment (Anticipated): 50
• Phase: Phase 2

Contacts and Locations

Study Locations

• Spain
  • Alicante, Spain
    • Hospital General de Alicante
  • Valencia, Spain
    • Hospital General de Valencia
  • Comunidad Valenciana
    • Alcoy, Comunidad Valenciana, Spain, 03804
      • Hospital Virgen de los Lirios
    • Castellón, Comunidad Valenciana, Spain, 12002
      • Hospital de Castellón
    • Elda, Comunidad Valenciana, Spain, 03600
      • Hospital de Elda
    • Manises, Comunidad Valenciana, Spain, 46940
      • Hospital de Manises
    • Sagunto, Comunidad Valenciana, Spain, 46520
      • Hospital de Sagunto
    • San Juan, Comunidad Valenciana, Spain, 03550
      • Hospital San Juan
    • Valencia, Comunidad Valenciana, Spain, 46026
      • Hospital U. y P. La Fe
    • Xátiva, Comunidad Valenciana, Spain, 46800
      • Hospital Lluis Alcanyis

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 70 years to 85 years (Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: Grupo de Investigación y Divulgación Oncológica
• Investigators: Principal Investigator: Oscar Juan Vidal, Dr., Grup d'investigació i divulgació en oncologia

Publications and helpful links

Helpful Links

• web of Sponsor

Study record dates

Study Major Dates

• Study Start: August 1, 2013
• Primary Completion (Actual): June 1, 2015
• Study Completion (Anticipated): August 1, 2017

Study Registration Dates

• First Submitted: October 14, 2013
• First Submitted That Met QC Criteria: November 4, 2013
• First Posted (Estimate): November 11, 2013

Study Record Updates

• Last Update Posted (Actual): February 27, 2017
• Last Update Submitted That Met QC Criteria: February 24, 2017
• Last Verified: February 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Carboplatin; Paclitaxel; Bevacizumab
• Other Study ID Numbers: GIDO1201

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO