Locally Advanced or Metastatic EGFR mutated, "T790M undetectable or unknown" Non Small Cell Lung Cancer (Stage IIIB-IV) MedDRA version: 21.1 Level: PT Classification code 10061873 Term: Non-small cell lung cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 21.1 Level: PT Classification code 10029521 Term: Non-small cell lung cancer stage IIIB System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl c
Conditions
Interventions
Trade Name: Tagrisso
Product Name: osimertinib
Product Code: AZD9291
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Osimertinib
CAS Number: 1421373-65-0
Current Sponsor code: codice ATC
Sponsors
AZIENDA OSPEDALIERO - UNIVERSITARIA "POLICLINICO - VITTORIO EMANUELE"
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Provision of signed, written and dated informed consent prior to any study specific procedures 2. Male/female >18 years of age. 3. Patients must have EITHER • Histologically or cytologically documented NSCLC who present with Stage IIIB/Stage IV disease (according to Version 7of the International Association for the Study of Lung Cancer Staging Manual in Thoracic Oncology [IASLC Staging Manual in Thoracic Oncology]), OR • Recurrent or progressive disease following multimodal therapy (radiation therapy, surgical resection, or definitive chemoradiation therapy for locally advanced disease). 4. Documented EGFR mutations which are known to be related with susceptibility to EGFR-TKIs (including G719X, exon 19 deletion, L858R, and L861Q). 5. Disease progression or recurrence after both a first line TKI and a subsequent chemotherapy regimen. All cytotoxic agents approved for the treatment of NSCLC are permitted, alone or in combination. 6. Inaccessible tumour for biopsy, medical contraindications to biopsy procedures, declined tumor biopsy at the time of disease progression, insufficent tumor tissue for T790M mutation testing or inconclusive testing result by local or central methods (Definition of T790M undetectable or unknown). 7. Absence of EGFR T790M resistance mutation on tumour sample if a biopsy was performed at the time of progression to EGFR TKI. 8. Measurable disease, at least 1 lesion, not previously irradiated, which can be accurately measured at baseline as =10 mm in the longest diameter (except lymph nodes that must have short axis =15 mm) with CT or MRI and which is suitable for accurate repeated measurements per RECIST v1.1 guidelines. 9. ECG recording at baseline showing absence of any cardiac abnormality as per exclusion criterion #10 10. World Health Organization (WHO) performance status 0-2. 11. Patients must have a life expectancy = 12 weeks. 12. Females patients of childbearing potential must be using adequate contraceptive measures from the time of screening until 3 months after discontinuing AZD9291, should not be breast feeding and must have a negative pregnancy test prior to start of dosing if of child-bearing potential or must have evidence of non-child-bearing potential by fulfilling one of the following criteria at screening: • Post-menopausal defined as aged more than 50 years and amenorrheic for at least 12 months following cessation of all exogenous hormonal treatments • Women under 50 years old would be consider postmenopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and with LH and FSH levels in the post-menopausal range for the institution • Documentation of irreversible surgical sterilisation by hysterectomy, bilateral oophorectomy or bilateral salpingectomy but not tubal ligation. Acceptable methods of contraception include total and true sexual abstinence, tubal ligation, intrauterine device (IUD), intrauterine hormone-releasing system (IUS), and vasectomized partner. All hormonal methods of contraception should be used in combination with the use of a condom by their male sexual partner for intercourse. 13. Male patients should be willing to use barrier contraception, during the trial and for a washout period of 4 months. Patients should not father a child for 6 months after completion of AZD9291 treatment. Patients should refrain from donating sperm from the start of dosing until 6 months after discontinuing AZD9291 treatment. If male p
Exclusion criteria
Exclusion criteria: Involvement in the planning and/or conduct of the study (applies to both sponsor staff and/or staff at the study site) Previous treatment with AZD9291 Detection of T790M mutation in tissue or blood (liquid biopsy) Primary resistance to previous TKI therapy defined as progression disease at the first radiologic tumour assessment Receipt of the last dose of chemotherapy within 21 days of the first administration of study drug Patients currently receiving (or unable to stop use prior to receiving the first dose of study treatment) medications or herbal supplements known to be potent inhibitors of CYP3A4 (at least 1 week prior) and potent inducers of CYP3A4 (at least 3 week prior). All patients must try to avoid concomitant use of any medications, herbal supplements and/or ingestion of foods with known inducer/inhibitory effects on CYP3A4 Any evidence of severe or uncontrolled systemic diseases, including uncontrolled hypertension and active bleeding diatheses, which in the investigator’s opinion makes it undesirable for the patient to participate in the trial or which would jeopardise compliance with the protocol, or active infection including hepatitis B,hepatitis C and human immunodeficiency virus (HIV). Screening for chronic conditions is not required Symptomatic, not yet treated with surgery and/or radiation CNS metastases neurologically unstable.Patients with previously diagnosed and treated CNS metastases or spinal cord compression may be considered if they have evidence of clinically stable disease (no steroid therapy or steroid dose being tapered) for at least 14 days Past medical history of ILD,drug-induced ILD,radiation pneumonitis requiring steroid treatment, or any evidence of clinically active ILD Any of the following cardiac criteria: Mean resting corrected QT interval (QTcF) > 470 ms using Fredericia’s formula Any clinically important abnormalities in rhythm,conduction or morphology of resting ECG (e.g.,complete left bundle branch block, third degree heart block,second degree heart block) Any factors that increase the risk of QTc prolongation or risk of arrhythmic events Any unresolved toxicities from prior therapy greater than CTCAE grade 1 at the time of starting study treatment with the exception of alopecia and grade 2, prior platinum-therapy related neuropathy. History of any other malignancy (other than curatively treated cervical cancer in situ, non-melanoma skin cancer, superficial bladder tumors Ta [non invasive tumor] and TIS [carcinoma in situ]) unless it has been definitively treated with no on-going therapy or evidence of relapse or recurrence within the past 3 years. Inadequate bone marrow reserve or organ function as demonstrated by any of the laboratory values Refractory nausea and vomiting, chronic gastrointestinal diseases,inability to swallow the formulated product or previous significant bowel resection that would preclude adequate absorption of AZD9291 History of hypersensitivity to excipients of AZD9291 or to drugs with a similar chemical structure or class to AZD9291 Females of childbearing potential (those who are not surgically sterilized or postmenopausal for at least 1 year) will be excluded from participation in the study if they meet any one of the following conditions:are currently pregnant or have a positive result on the urine pregnancy test at the Baseline Visit or intend to become pregnant during the study treatment period or Males not willing to use barrier methods of contraception, during
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine the anti-tumor efficacy of osimertinib administered to ¿T790M undetectable or unknown¿ NSCLC patients after an EGFR TKI (1¿line) and a subsequent chemotherapy (2¿line), as measured by objective response rate (ORR). ;Secondary Objective: -To determine secondary measures of clinical efficacy of osimertinib administered to ¿T790M undetectable or unknown¿ NSCLC patients after an EGFR TKI (1¿line) and a subsequent chemotherapy (2¿line), including progression-free survival (PFS) and overall survival (OS); -To assess the safety and tolerability profile of osimertinib;Primary end point(s): Objective response rate ORR;Timepoint(s) of evaluation of this end point: Objective response will be assessed for single patient during visits planned every 6 weeks (± 7 days) starting from the date of the first administration of study drug until objective disease progression according to RECIST version 1.1 | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: Patient survival will be evaluated throughout the study period.; Drug safety will be evaluated throughout the study period; Clinical assessments and laboratory tests will be performed during planned visits and during additional visits if considered necessary by the investigator.; Visit 1, Visit 2 and then on the end of treatment visit;Secondary end point(s): Progression-free survival (PFS) and overall survival (OS) ; Adverse events/serious adverse events (AEs/SAEs); Vital signs and collection of clinical chemistry/haematology parameters; Mutational analysis of a panel of genes involved in resistance to EGFR-TKIs | — |
Countries
Italy
Contacts
Public ContactDirezione Unifarm
Consorzio Universitario Unifarm
Outcome results
None listed