Efficacy of Osimertinib in Treatment-Naïve Patients with EGFR Mutant NSCLC Stratified by TP53 Mutational Status
- Trial ID
- 2024-517424-18-00
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to determine the efficacy of **osimertinib** in terms of progression-free survival (PFS) in treatment-naïve patients with advanced epidermal growth factor receptor (EGFR) mutant non-small cell lung cancer (NSCLC), stratified by **TP53** mutational status. This objective is clinically relevant as it aims to evaluate the potential of osimertinib to improve PFS, which is a critical endpoint in the management of advanced NSCLC, potentially leading to better patient outcomes and informing treatment strategies based on genetic profiling.
Participants
The clinical trial involves participants diagnosed with **EGFR mutant non-small cell lung cancer (NSCLC)**, stratified by TP53 mutational status. The study population includes both male and female subjects aged 18 years and older. Participants are required to have locally advanced or metastatic NSCLC that is not suitable for curative surgery or radiotherapy, with confirmed EGFR exon 19 deletion or exon 21 p. L858R mutations. The trial does not include a vulnerable population. Participants must have a World Health Organization performance status of 0-1 and a life expectancy of at least 12 weeks. They should be treatment-naïve for locally advanced or metastatic NSCLC and eligible for first-line treatment with osimertinib. The sponsor has not provided information regarding the total number of participants. Lifestyle considerations such as diet and physical activity are not specified. Key inclusion criteria include the provision of informed consent, the ability to comply with the study protocol, and the availability of measurable lesions for assessment. Exclusion criteria are not detailed in the provided data.
Plans and Procedures
The clinical trial is designed to evaluate the **efficacy** of **osimertinib** in treatment-naïve patients with **EGFR mutant non-small cell lung cancer (NSCLC)**, considering the **TP53 mutational status**. This study is a **randomized, double-blind, controlled trial** and is categorized as a Phase IV study. The trial is expected to commence recruitment on September 1, 2021, and is estimated to conclude by December 30, 2025. Participants will be administered TAGRISSO 80 mg film-coated tablets orally, with a maximum daily dose of 80 mg, over a treatment period of up to 14 days.
The trial will include several study visits, beginning with an inclusion (screening) visit to confirm eligibility based on specific criteria, such as age, disease status, and prior treatment history. Participants must provide informed consent and meet the inclusion criteria, including having a life expectancy of at least 12 weeks and a World Health Organization performance status of 0-1. The screening visit will also involve the provision of an unstained, archived tumor tissue sample for central analysis. Following the screening, participants will undergo regular follow-up visits to monitor treatment efficacy and safety, with assessments including computed tomography (CT) or magnetic resonance imaging (MRI) to measure tumor response.
The end-of-study visit will occur at the conclusion of the treatment period or upon early termination. Participants may be withdrawn from the study if they experience significant adverse effects, fail to comply with the protocol, or if the investigator deems it necessary for their safety. The expected length of participant involvement is contingent upon the treatment period and follow-up assessments, with the primary endpoint being the determination of progression-free survival (PFS) in relation to the TP53 mutational status. The study aims to provide valuable insights into the treatment of advanced EGFR mutant NSCLC with osimertinib.
Treatment
The clinical trial involves the administration of **osimertinib**, marketed under the name TAGRISSO, as the experimental medication. TAGRISSO is provided in the form of **film-coated tablets**, each containing 80 mg of the active substance, osimertinib. The tablets are intended for **oral use**. Participants in the trial will receive a daily dose of 80 mg, with the maximum treatment period set at 14 days. The pharmaceutical formulation is not specifically designed for pediatric use. Osimertinib is a chemical substance, also known by the synonym AZD9291, and is classified under the ATC code L01XE35. The medication is manufactured by AstraZeneca AB and holds the marketing authorization number EU/1/16/1086/002.
In this study, osimertinib is the sole investigational product, and no non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments are utilized. The trial aims to evaluate the efficacy of osimertinib in treatment-naïve patients with advanced EGFR mutant non-small cell lung cancer (NSCLC), with a focus on the TP53 mutational status. Participant compliance with the dosing regimen will be monitored throughout the study to ensure adherence to the prescribed treatment schedule.
Efficacy
The efficacy of **osimertinib** in the treatment of patients with advanced EGFR mutant non-small cell lung cancer (NSCLC) will be assessed in this clinical trial. The primary endpoint for evaluating efficacy is progression-free survival (PFS), specifically in relation to the TP53 mutational status of the patients. This endpoint will provide insights into the duration patients remain free from disease progression while on treatment with osimertinib.
Inclusion and Exclusion Criteria
Inclusion Criteria
- o Provision of informed consent prior to any study specific procedures. o Patients (male/female) must be > 18 years of age. o Locally advanced or metastatic EGFR mutant NSCLC, not amenable to curative surgery or radiotherapy with confirmation of the presence of EGFR exon 19 deletion or exon 21 p. L858R. o Mandatory provision of an unstained, archived tumour tissue sample in a quantity sufficient to allow central analysis. o Patients must be treatment-naïve for locally advanced or metastatic NSCLC and eligible to receive first-line treatment with osimertinib. Prior adjuvant and neoadjuvant therapy is permitted (chemotherapy, radiotherapy) if at least 6 months has elapsed between the end of chemotherapy and enrolment. o World Health Organization (WHO) performance status 0-1 with no deterioration over the previous 2 weeks prior to baseline or day of first dosing. o Patients must have a life expectancy = 12 weeks. o Females should be using adequate contraceptive measures, should not be breast feeding and must have a negative pregnancy test prior to start of dosing if of childbearing 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. o Male patients should be willing to use barrier contraception. o Patient is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up. o At least one lesion, not previously irradiated, that can be accurately measured at baseline as = 10 mm in the longest diameter (except lymph nodes which must have short axis = 15 mm) with computed tomography (CT) or magnetic resonance imaging (MRI) and which is suitable for accurate repeated measurements.
Exclusion Criteria
- Subjects(sponsor and/or enrollment center staff)involved in planning and/or conducting the study,Previous treatment with Osimertinib or any other anti-EGFR target drug,Treatment with any other experimental drug in the previous3months of enrollment,Patients who are currently being treated (or are unable to stop treatment before receiving the first dose of the experimental drug) with medications or homeopathic remedies included in Annex6,Any residual toxicity from previous treatments that is grade>1at the time of enrollment, with the exception of alopecia. Grade2 residual toxicity is permissible for platinum-related neuropathy,Concomitant uncontrolled or severe systemic disease, including hypertension or haemorrhagic diathesis, active hepatitisB infection, hepatitisC orHIV.Patients with HBV are only eligible for inclusion if they meet all the following criteria:Demonstrated absence of HCV co-infection or history ofHCVco-infection,Demonstrated absence of HIV infection,Participants with active HBV infection are eligible if they are:Receiving anti-viral treatment for at least 6 weeks prior to study treatment,HBVDNA is suppressed to <100 IU/mL and transaminase levels are belowULN.Participants with a resolved or chronicHBVinfection are eligible if they are:Negative for HBsAg and positive for hepatitis B core antibody [anti-HBcIgG or total antiHBcAb]. In addition, patients must be receiving anti-viral prophylaxis for2-4 weeks prior to study treatment.or Positive for HBsAg, but for>6 months have had transaminases levels belowULNandHBVDNAlevels below<100IU/mL(are in an inactive carrier state).Patients must be receiving anti-viral prophylaxis for2-4weeks prior to study treatment.Patients with HIV are only eligible for inclusion if they meet all the following criteria:Demonstrated absence ofHBV/HCVco-infection,Undetectable viralRNA load for 6months,CD4+count of>350cells/µL,No history of AIDS-defining opportunistic infection within the past 12months,Stable for at least 4 weeks on the same anti-HIV medications,Patients with spinal cord compression or symptomatic and / or unstable brain metastases. Corticosteroid therapy is allowed for the control of brain metastases as long as they are asymptomatic and treated with the same dosage for at least 14days before starting treatment with Osimertinib,Personal history of pulmonary interstitial disease, actinic pneumonia requiring corticosteroid therapy, or any evidence of active interstitial disease,Any cardiac alteration between:Correct QT interval (using Fredericia's formula)>470 msec or the presence of risk factors that prolong the QT interval (electrolyte changes),Any clinically significant alteration of the rhythm, conduction or alterations of the restingECG(e.g., complete left branch block),Inadequate blood chemistry values:Absolute neutrophil count <1.5x109/L,Platelets <100x109/L,Hemoglobin <9g/dL,Alanine aminotransferase and aspartate aminotransferase> 2.5 times the upper limit,(ULN) in the absence of liver metastases> 5 times ULN in the presence of liver metastases,Total bilirubin1.5timesULNin the absence of liver metastases or>3timesULNin the presence of Gilbert's syndrome (indirect hyperbilirubinemia) or liver metastases Creatinine>1.5timesULNconcomitant with a creatinine clearance<50ml/min (using theCockcroft andGault formula),Refractory nausea or vomiting, or any gastrointestinal disease that does not allow the intake absorption of Osimertinib,Second active neop or previous treat for other neop for which at least 6 months have elapsed since the first day of Osimertinib (or at least2 years in case of bone marrow transplant),Patients with other medical conditions or serious clinical conditions,including those with uncontrolled active infection,History of hypersensitivity to osimertinib or to chemically similar drugs or to any excipient,Wom who are pregnant or breastfeeding,Decision by the Inv not to enroll the patient who is unable to comply with the procedures envisaged by the study
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Italy | Not Recruiting | 01 Sept 2021 | 54 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
TAGRISSO 80 mg film-coated tablets | Test | FILM-COATED TABLETS | ORAL USE | 80 | 14 | PRD3702450 |