EGFR mutated NSCLC patients with oligometastatic disease MedDRA version: 21.1 Level: PT Classification code 10029522 Term: Non-small cell lung cancer stage IV System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Trade Name: TAGRISSO
Product Name: TAGRISSO 80 mg
Product Code: [TAGRISSO 80 mg]
Pharmaceutical Form: Tablet
INN or Proposed INN: osimertinib
Current Sponsor code: TAGRISSO 80 mg
Concentration unit: m
Sponsors
GRUPPO ONCOLOGICO ITALIANO DI RICERCA CLINICA (GOIRC)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Previously untreated advanced EGFR-mutated NSCLC patient, candidate to receive osimertinib as first-line treatment 2. Male or female and = 18 years of age 3. Life expectancy = 12 weeks 4. Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 to 1 5. Disease staging with FDG-PET and brain imaging (CT scan or MRI) evidencing an oligometastatic disease, defined according to EORTC criteria (from 1 to 5 metastatic lesions) 6. Tumor disease susceptible of radiotherapy treatment to primary tumor (T size < 7 cm) and metastatic sites, considering normal tissue dose constraints 7. Adequate hematological function defined by white blood cell (WBC) count = 2.500/mm3 with absolute neutrophil count (ANC) = 1.500/mm3, platelet count =100,000/mm3 and hemoglobin = 9 g/dL 8. Adequate hepatic function defined by a total bilirubin = 1.5 x the upper limit of normal (ULN) range (except subjects with Gilbert Syndrome, who can have total bilirubin < 3.0 mg/dL), serum alanine aminotransferase ALT) and aspartate aminotransferase (AST) = 2.5 x ULN (= 5 if liver function test elevations are due to liver metastases) 9. Adequate renal function defined by a serum creatinine = 1.5 x ULN or an estimated creatinine clearance of 50 mL/minute for patients with creatinine levels above institutional limits (if using the Cockcroft-Gault formula) 10. Stable medical condition, including the absence of acute exacerbations of chronic illnesses, serious infections, or major surgery within 4 weeks before registration, and otherwise noted in other inclusion/exclusion criteria 11. For Females: must be using highly effective contraceptive measures and must have a negative pregnancy test prior to start of dosing if of childbearing potential, or must have evidence of non-childbearing 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 considered postmenopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and with luteinizing hormone and follicle-stimulating hormone levels in the post-menopausal range for the institution; - Documentation of irreversible surgical sterilization by hysterectomy, bilateral oophorectomy, or bilateral salpingectomy but not tubal ligation. Women of childbearing potential must use highly effective contraception measures for a minimum of 2 weeks before entering the trial, during the entire study treatment period and for a period of 6 weeks after the last dose of study drug, or agree to practice true abstinence, when this is in line with the preferred and usual lifestyle of the subject. 12. For Males: even if surgically sterilized (i.e. post-vasectomy status) agree to practice effective barrier contraception, with a failure rate of less than 1% per year, during the entire study treatment period and for a period of 16 weeks after the last dose of investigational product, or practice true abstinence, when this is in line with the preferred and usual lifestyle of the subject 13. Ability to comply with protocol requirements 14. The patient or the patient’s legal representative is able to provide written informed consent. Voluntary written consent must be given before performance of any study-related procedure not part of standard medical care, with the understanding that the patient may
Exclusion criteria
Exclusion criteria: 1. ECOG PS > 1 2. Concurrent anticancer treatment, immune therapy or cytokine therapy 3. History of hypersensitivity to active or inactive excipients of osimertinib or drugs with a similar chemical structure or class to osimertinib 4. Previous treatment with EGFR-TKI 5. Patients who have received treatment with an investigational drug within five half-lives of the compound or 3 months prior the screening visit 6. Patients currently receiving medications or herbal supplements known to be strong inducers of cytochrome P450 (CYP) 3A4. 7. Patients with 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 8. Patients with any evidence of severe or uncontrolled systemic diseases, including uncontrolled hypertension and active bleeding diatheses 9. Patients with refractory nausea and vomiting, chronic gastrointestinal diseases, inability to swallow the formulated product, or previous significant bowel resection that would preclude adequate absorption of osimertinib 10. Patients with any of the following cardiac criteria: a. Mean resting corrected QTc > 470 msec, obtained from ECGs, using the screening clinic ECG machine-derived QTc value b. Any clinically important abnormalities in rhythm, conduction, or morphology of resting ECG c. Patients with any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as the following electrolyte abnormalities, heart failure, congenital long QT syndrome, family history of long QT syndrome, or unexplained sudden death under 40 years of age in first-degree relatives or any concomitant medication known to prolong the QT interval and cause Torsades de Pointes (TdP): d. Hypokalemia (serum potassium < 3.5 mmol/L) e. Hypomagnesemia (serum magnesium < 0.7 mmol/L) f. Hypocalcemia (corrected serum calcium < 2.1 mmol/L) 11. Previous thoracic radiotherapy treatment 12. Patients with central nervous system involvement 13. Patients with contraindications to radiotherapy treatment, such as the presence of severe chronic obstructive pulmonary disease (COPD), the presence of idiopathic pulmonary fibrosis, active autoimmune diseases or in case of inability to maintain the position for radiotherapy treatment 14. Patients past medical history of interstitial lung disease, drug-induced interstitial lung disease or any evidence of clinically active interstitial lung disease. 15. Not adequate lung pulmonary functions with a FEV1< 40% and/or an absolute value < 1.5 l/min 16. Major surgery for any reason within 4 weeks from randomization and/or if the subject has not fully recovery from the surgery within 4 weeks of registration. 17. Patients with other concurrent neoplasms 18. Subjects with previous malignancies 19. Any medical condition, within 6 months before receiving the first dose of study drug, considered relevant by Investigator. Chronic stable atrial fibrillation on stable anticoagulant therapy is allowed. Patients who present particular clinical conditions or relevant comorbidity may be enrolled into the study upon discussion with the Study Coordinator 20. Any severe infection, including COVID-19, within 4 weeks prior to initiation of study treatment, including, but not limited to, hospitalization for complications of infections 21. For female subjects: positive serum pregnancy test, pregnancy or breast feeding 22. Unwilling or unable to comply
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the efficacy of a first-line Osimertinib plus consolidation radiotherapy compared with standard Osimertinib alone by assessment of progression-free survival (PFS) in oligometastatic NSCLC EGFR mutated patients.;Secondary Objective: •Objective Response Rate (ORR) according to RECIST, version 1.1 •Time to new lesion progression (TNP), defined as the time from randomization to appearance of new lesions •Time to treatment failure (TTF), defined as the time from randomization to osimertinib discontinuation, irrespective of disease progression •Overall survival (OS), defined as the time from randomization to death from any cause •Toxicity according NCIC-CTCAE version 5.0 •Quality of life evaluated with European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)- C30 and EORTC QLQ-LC13;Primary end point(s): The primary endpoint is the progression-free survival (PFS) as determined by investigator assessments, according to RECIST, version 1.1. Progression-free survival is defined as the time from randomization to objective disease progression or death from any cause in the absence of progression, irrespective of withdrawal from the trial or treatment with another anticancer therapy before progression. The primary endpoint will evaluate the efficacy of experimental treatment in terms of hazard ratio of progression at the 18th month form the patient’s randomization.;Timepoint(s) of evaluation of this end point: 24-months of enrolment and each subject will followed-up for a maximum of 30 months after the randomization in the study. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Objective response: Objective response (OR) is defined as a complete response (CR) or a partial responses (PR), based on the Investigator’s assessment, and will be measured according to standard RECIST criteria v1.1. The following paragraphs are a quick reference to the RECIST criteria. - Time to treatment failure: Time to treatment failure (TTF) is calculated as the interval from the randomization to discontinuation of osimertinib treatment for any reason, including disease progression, treatment toxicity, and death. - Time to new lesion progression: Time to new lesion progression (TNP) is calculated as the interval from the randomization to appearance of new lesions. - Overall survival: Overall survival (OS) is defined as the time from the date of randomization to the date of death, whatever the cause. The follow-up of patients still alive will be censored at the moment of last visit/contact.;Timepoint(s) of evaluation of this end point: followed-up for a maximum of 30 months after the randomization in the study. | — |
Countries
Italy
Contacts
Public ContactAzienda Ospedaliero-Universitaria d
Goirc
Outcome results
None listed