Efficacy Study of Osimertinib in Treatment-naïve Patients With EGFR Mutant NSCLC According to TP53 Mutational Status.

Trial Title: Efficacy Study of Osimertinib in Treatment-naïve Patients With EGFR Mutant NSCLC According to TP53 Mutational Status.

NCT ID: NCT05785208

Condition: Non Small Cell Lung Cancer

Conditions: Official terms:
Carcinoma, Non-Small-Cell Lung
Osimertinib

Conditions: Keywords:
TP53
EGFR
NSCLC
Osimertinib

Study type: Interventional

Study phase: Phase 4

Overall status: Recruiting

Study design:

Allocation: Non-Randomized

Intervention model: Parallel Assignment

Primary purpose: Treatment

Masking: None (Open Label)

Intervention:

Intervention type: Drug
Intervention name: Osimertinib
Description: Osimertinib will be administered at a dose of 80 mg daily until disease progression
Arm group label: ARM A: TP53 wilde-type
Arm group label: ARM B: TP53 mutant

Summary: This is a prospective, biomarker-driven, open-label, clinical trial of osimertinib in treatment- naïve patients with EGFR mutant NSCLC, to evaluate the efficacy of osimertinib according to the TP53 mutational status.

Criteria for eligibility:
Criteria:
Inclusion Criteria: - Provision of informed consent prior to any study specific procedures. - Patients (male/female) must be > 18 years of age. - 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. - Mandatory provision of an unstained, archived tumour tissue sample in a quantity sufficient to allow central analysis. - Patients must be treatment-naïve for locally advanced or metastatic NSCLC and eligible to receive first-line treatment with osimertinib. Prior adjuvant and neo-adjuvant therapy is permitted (chemotherapy, radiotherapy) if at least 6 months has elapsed between the end of chemotherapy and enrolment. - World Health Organization (WHO) performance status 0-2. - Patients must have a life expectancy ≥ 12 weeks. - Females should be using adequate contraceptive measures, should not be breastfeeding 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: 1. Post-menopausal defined as aged more than 50 years and amenorrheic for at least 12 months following cessation of all exogenous hormonal treatments. 2. 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. 3. Documentation of irreversible surgical sterilisation by hysterectomy, bilateral oophorectomy or bilateral salpingectomy but not tubal ligation. - Male patients should be willing to use barrier contraception. - 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. - 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: - 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 osimertinib or other drugs targeting EGFR. - Treatment with an investigational drug within five half-lives of the compound or 3 months, whichever is greater. - Patients currently receiving (or unable to adequately stop use prior to receiving the first dose of study treatment) medications or herbal supplements included in Annex 6 (Guidance Regarding Potential Interactions with Concomitant Medications). - 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. - 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. - Patients with spinal cord compression, symptomatic and unstable brain metastases except for those patients who have completed definitive therapy, and have had a stable neurological status for at least 2 weeks after completion of definitive therapy. Patients may be on corticosteroids to control brain metastases if they have been on a stable dose for 2 weeks (14 days) prior to the start of study treatment and are clinically asymptomatic. - Past medical history of ILD, drug-induced ILD, radiation pneumonitis requiring steroid treatment, or any evidence of clinically active ILD. - Inadequate bone marrow reserve or organ function as demonstrated by any of the following laboratory values: 1. Absolute neutrophil count <1.5 x 109/L. 2. Platelet count <100 x 109/L. 3. Haemoglobin <90 g/L. 4. Alanine aminotransferase >2.5 times the upper limit of normal (ULN) if no demonstrable liver metastases or >5 times ULN in the presence of liver metastases. 5. Aspartate aminotransferase >2.5 times ULN if no demonstrable liver metastases or >5 times ULN in the presence of liver metastases. 6. Total bilirubin >1.5 times ULN if no liver metastases or >3 times ULN in the presence of documented Gilbert's Syndrome (unconjugated hyperbilirubinemia) or liver metastases. 7. Creatinine >1.5 times ULN concurrent with creatinine clearance <50 ml/min (measured or calculated by Cockcroft and Gault equation); confirmation of creatinine clearance is only required when creatinine is >1.5 times ULN. - Any of the following cardiac criteria: 1. Mean resting corrected QT interval (QTc using Fredericia's formula) > 470 msec. 2. Any clinically important abnormalities in rhythm, conduction or morphology of resting ECG (e.g., complete left bundle branch block, third degree heart block, and second degree heart block). 3. Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, electrolyte abnormalities (including serum/plasma potassium < LLN, serum/plasma magnesium < LLN, and serum/plasma calcium 6 months prior and/or bone marrow transplant > 2 years prior to first day of study treatment. - Patients with other serious diseases or clinical conditions, including but not limited to uncontrolled active infection and any other serious underlying medical processes that could affect the patient's capacity to participate in the study. - History of hypersensitivity to osimertinib (or drugs with a similar chemical structure or class to osimertinib) or any excipients of these agents. - Males and females of reproductive potential who are not using an effective method of birth control and females who are pregnant or breastfeeding or have a positive (urine or serum) pregnancy test prior to study entry. - Judgment by the Investigator that the patient should not participate in the study if the patient is unlikely to comply with study procedures, restrictions and requirements.

Gender: All

Minimum age: 18 Years

Maximum age: N/A

Healthy volunteers: No

Locations:

Facility:
Name: Azienda Ospedaliero-Universitaria Ospedali Riuniti

Address:
City: Ancona
Zip: 60020
Country: Italy

Status: Suspended

Facility:
Name: IRCCS Istituto Tumori Giovanni Paolo II

Address:
City: Bari
Zip: 70124
Country: Italy

Status: Suspended

Facility:
Name: Azienda Ospedaliero-Universitaria Careggi

Address:
City: Firenze
Zip: 50134
Country: Italy

Status: Suspended

Facility:
Name: Ospedale Universitario di Parma

Address:
City: Parma
Zip: 44129
Country: Italy

Status: Suspended

Facility:
Name: Ospedale San Camillo de Lellis

Address:
City: Rieti
Zip: 02100
Country: Italy

Status: Suspended

Facility:
Name: Università Policlinico Tor Vergata

Address:
City: Rome
Zip: 00133
Country: Italy

Status: Suspended

Facility:
Name: Policlinico Umberto I

Address:
City: Rome
Zip: 00161
Country: Italy

Status: Suspended

Facility:
Name: Fondazione Policlinico Gemelli IRCCS

Address:
City: Rome
Zip: 00168
Country: Italy

Status: Recruiting

Contact:
Last name: Emilio Bria, Professor

Phone: 0630155202

Phone ext: +39
Email: emilio.bria@policlinicogemelli.it

Facility:
Name: Ospedale San Giovanni-Addolorata

Address:
City: Rome
Zip: 00184
Country: Italy

Status: Suspended

Facility:
Name: Ospedale San Luigi

Address:
City: Turin
Zip: 10043
Country: Italy

Status: Suspended

Facility:
Name: Università degli Studi di Verona

Address:
City: Verona
Zip: 37129
Country: Italy

Status: Suspended

Start date: June 28, 2022

Completion date: October 31, 2025

Lead sponsor:
Agency: Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Agency class: Other

Source: Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Record processing date: ClinicalTrials.gov processed this data on November 12, 2024

Source: ClinicalTrials.gov page: https://clinicaltrials.gov/ct2/show/NCT05785208