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

G

Grupo de Investigación y Divulgación Oncológica

Status and phase

Unknown
Phase 2

Conditions

Non-small Cell Lung Cancer (NSCLC)

Treatments

Biological: bevacizumab, carboplatin and paclitaxel

Study type

Interventional

Funder types

Other

Identifiers

NCT01980472
GIDO1201

Details and patient eligibility

About

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

Full 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.

Enrollment

50 estimated patients

Sex

All

Ages

70 to 85 years old

Volunteers

No Healthy Volunteers

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

Trial design

Primary purpose

Other

Allocation

N/A

Interventional model

Single Group Assignment

Masking

None (Open label)

50 participants in 1 patient group

bevacizumab, carboplatin and paclitaxel
Experimental group
Description:
bevacizumab, carboplatin and paclitaxel
Treatment:
Biological: bevacizumab, carboplatin and paclitaxel

Trial contacts and locations

10

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Data sourced from clinicaltrials.gov

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