A research study to compare the combined treatment of osimertinib and bevacizumab with osimertinib treatment alone in patients with lung cancer that has progressed or spread to other parts of the body (metastatic) and with confirmed specific gene mutations (changes) in the epithelial growth factor receptor (EGFR)

Phase 1

Conditions: Patients with locally advanced or metastatic (stage IIIb-IVb) EGFRm (exon 19 deletion or exon 21 L858R) NSCLC with T790M resistance mutation at progression on prior EGFR TKI therapy
MedDRA version: 21.1Level: PTClassification code 10029521Term: Non-small cell lung cancer stage IIIBSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA version: 21.1Level: PTClassification code 10059515Term: Non-small cell lung cancer metastaticSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA version: 21.1Level: PTClassification code 10061873Term: Non-small cell lung cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Therapeutic area: Diseases [C] - Cancer [C04]

Registration Number: EUCTR2016-002029-12-NL

Lead Sponsor: ETOP (European Thoracic Oncology Platform)

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 154

Inclusion Criteria

• NSCLC, stage IIIb/IIIc (not amenable to radical therapy) or IVa/IVb according to 8th TNM classification, after progression following prior EGFR TKI (erlotinib, gefitinib, dacomitinib or afatinib) therapy as the most recent treatment regimen.
• Pathological diagnosis of predominantly non-squamous NSCLC.
• Maximum of one line of previous platinum based chemotherapy.
• Histological or cytological confirmation of EGFRm (exon19 deletion or exon 21 L858R).
• Locally confirmed T790M mutation determined from biopsy (preferred) or on circulating tumour DNA, documented in tissue, plasma or serum after disease progression on the most recent EGFR TKI regimen.
• Plasma, serum, and tumour (preferred) tissue or cytology (if biopsy was taken and FFPE tumor material is not yet fully depleted) after disease progression on the most recent EGFR TKI treatment available for central confirmation of T790M.
• Measurable or evaluable disease
• Adequate haematological, renal and liver function
• Performance status 0-2

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 154
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 154

Exclusion Criteria

• Patients with mixed NSCLC with predominantly squamous cell cancer, or with any small cell lung cancer (SCLC) component.
• Symptomatic or active central nervous system metastases, as indicated by clinical symptoms, cerebral edema, and/or progressive growth.
• Previous treatment with osimertinib and/or bevacizumab
• Patients currently receiving medications or herbal supplements known to be potent CYP3A4 inducers
• Any unresolved toxicities from prior therapy greater than CTCAE V 4.0 grade 1

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To assess the efficacy of the combination of osimertinib and bevacizumab versus osimertinib alone in terms of progression-free survival (PFS) assessed by RECIST 1.1.;Secondary Objective: To compare short and long term clinical efficacy outcomes as well as tolerability of the two treatments.;Primary end point(s): Progression-free survival (PFS) based on RECIST 1.1 criteria ;Timepoint(s) of evaluation of this end point: Time from the date of randomisation until documented progression or death, if progression is not documented

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): • Objective Response (OR), based on RECIST 1.1 criteria<br>• Disease control, defined as complete or partial response, or disease stabilisation, confirmed at subsequent radiological <br> assessment<br>•Adverse events graded by CTCAE V4.0<br>•Overall survival (OS)<br>;Timepoint(s) of evaluation of this end point: • OR : across all assessment time-points during the period from randomisation to termination of trial Treatment<br>• Disease control: across all assessment time-points during the period from randomisation to termination of trial Treatment<br>• AEs:from date of signature of informed consent until 30 days after all Trial Treatment discontinuation<br>• OS: time from the date of randomisation until death from any cause

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