A phase IIa clinical trial to evaluate the safety and efficacy of osirmertinib in first-line patients withadvanced or metastatic non-small cell lung cancer (AZENT study)

Phase 1

• Conditions: Patients diagnosed with stage IIIB or IV non-small cell lung cancer carrying the EGFR activating mutation and confirming concomitant T790M mutation during screening who have not received prior treatment for this advanced disease will be enrolled in this study. Patients are not eligible if they are candidates for local curative treatment.; MedDRA version: 19.0Level: PTClassification code 10029522Term: Non-small cell lung cancer stage IVSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 19.0Level: PTClassification code 10029521Term: Non-small cell lung cancer stage IIIBSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 19.0Level: PTClassification code 10059515Term: Non-small cell lung cancer metastaticSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2015-004828-66-ES
• Lead Sponsor: Medica Scientia Innovation Research (MedSIR ARO)

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2016-05-18
• Last Update Posted: 2 June 2020

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 73

Inclusion Criteria

Inclusion criteria
1.Patient aged 18 years or older.
2.Patients with histological confirmation of locally advanced or metastatic, non-squamous non-small cell lung cancer (NSCLC) with an activating EGFR mutation and concomitant T790M mutation who are not candidates for local curative treatment.
3.Patients with a M1a stage according to the TNM version 7 including M1a (malignant effusion) or M1b (distant metastasis), or locally advanced disease for which there is no curative treatment (including patients who progress after chemoradiotherapy in stage III disease).
4.Patients with a EGFR deletion or mutation in exon 19, exon 21 (L858R, L861Q) or exon 18 (G719X) and concomitant T790M mutation before treatment confirmed centrally.
5.ECOG (Eastern Cooperative Oncology Group) performance status less than or equal to 2.
6.Existence of measurable or evaluable disease (as per RECIST 1.1 criteria). Patients with asymptomatic and stable brain metastases are eligible for the study.
7.Possibility of obtaining sufficient tissue sample, via a biopsy or surgical resection of the primary tumor or metastatic tumor tissue, within the 60 days prior to study entry.
8.Life expectancy =12 weeks.
9.Adequate hematologic function: Absolute neutrophil count (ANC) > 1.5 x 109/L, platelet count > 100.0 x109/L and hemoglobin > 9.0 g/dL (> 6.2 mmol/L).
10.Adequate coagulation: INR = 1.5.
11.Adequate liver function: Total bilirubin < 1.5 × ULN, ALT and/or AST < 2.5 × ULN, alkaline phosphatase < 5 ULN, except in the presence of single bone metastases and in absence of any liver disorders.
12.Adequate renal function: Calculated creatinine clearance > 50 mL/min (Cockroft-Gault) and proteinuria < 2+ (dipstick).
13.Capacity to swallow, patient capable of completing treatment and accessible, ensuring proper follow-up.
14.Patients able to complete study and within geographical proximity allowing for adequate follow-up.
15.Resolution of all acute toxic effects of any previous anti-cancer therapy (which can only be adjuvant or neoadjuvant) or previous surgical interventions not exceeding grade ? 1 according to the NCI CTCAE version 4.0 (except for alopecia or other side effects that the investigator does not consider to be a risk to patient safety).
16.All men or women of childbearing potential must use a contraception method during the study treatment and for at least 12 months after the last dose of the study drug. Sexually active men and women of childbearing potential who are unwilling to use a contraception method are not eligible for the study.
17.The written informed consent (IC) must be signed and dated by the patient and the investigator before any study intervention takes place.
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 73
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 73

Exclusion Criteria

Any patient meeting ANY of the following criteria will be excluded from the study:
1.Locally advanced lung cancer candidate for curative treatment through radical surgery and/or radio(chemo)therapy.
2.Patients diagnosed with another lung cancer subtype, patients with mixed NSCLC with predominantly squamous cell cancer, or with any small-cell lung cancer component.
3.Patients with a EGFR deletion or mutation in exon 19, exon 21 (L858R, L861Q) or exon 18 (G719X) and concomitant T790M mutation before treatment that have not been confirmed centrally.
4.Patients who have received prior antineoplastic treatment for advanced disease.
5.Second active neoplasia; e.g. patients diagnosed with a potentially lethal cancer for which they may be receiving treatment (but are not obliged to do so).
6.Patients with just one measurable or evaluable tumor lesion that has been resected or irradiated prior to their enrollment in the study.
7.Medical history of Interstitial Lung Disease (ILD) induced by drugs, radiation pneumonitis requiring steroid treatment or any evidence of clinically active ILD.
8.Any of the following criteria:
•Corrected QT Interval (QTc) >470 msec, obtained from 3 ECGs at rest, using the QTc value determined according to the clinical screening ECG machine.
•Any clinically significant abnormality in ECG rhythm, conduction or morphology at rest.
•Any factor that increases the risk of QTc prolongation or risk of irregular heartbeat or sudden inexplicable death under the age of 40 in first-degree relatives or any concomitant medications that prolong the QT interval.
9.Uncontrolled, active or symptomatic metastases of CNS, carcinomatous meningitis or leptomeningeal disease indicated by known clinical symptoms, cerebral edema and/or progressive neoplasia. Patients with history of CNS metastasis or compression of the spinal cord are eligible if they have received local final treatment (e.g., radiotherapy, stereotactic surgery) and if they have remained clinically stable without using anticonvulsants and corticosteroids for a minimum of 4 weeks prior to the first day of study treatment.
10.Refractory nauseas and vomiting, chronic gastrointestinal disease, inability to swallow study drug or significant intestinal resection that restricts the adequate absorption of osimertinib (AZD9291).
11.Patients who have had a surgical procedure unrelated to the study within 7 days prior to the administration of the drug or a significant traumatic lesion during the 4 weeks prior to starting the administration of the study drug, patients who have not recovered from the side effects of any major surgery or patients who might need major surgery during the course of the study.
12.Pregnant or breastfeeding women. Women of childbearing potential, including women who had their last menstrual period within the last two years, must have a negative serum or urine pregnancy test in the 7 days prior to the start of the treatment.
13.Patients who are not willing to use an adequate contraception method until 12 months after the last dose of study treatment.
14.Patients with a serious concomitant systemic disorder (e.g., active infection, including HIV or heart disease) that is incompatible with the study (in the opinion of the investigator), history of bleeding diathesis or anticoagulant therapy (the use of low molecular weight heparin is permitted provided that it is used for prophylaxis).
15.Inability to swallow tablets.
16.Patients with a history of

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified