Evaluation of efficacy of gefitinib drug in patients with non-small cell tumors with EGFR and TP53 gene mutatio

Phase 1

• Conditions: on-small cell lung cancer (NSCLC) at the stageadvanced / metastatic with receptor sensitizing mutation for growth factorepidermal (EGFR); MedDRA version: 21.1Level: 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: EUCTR2017-002626-20-IT
• Lead Sponsor: AZIENDA OSPEDALIERA UNIVERSITARIA INTEGRATA VERONA

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2021-06-04
• Last Update Posted: 14 March 2022

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 54

Inclusion Criteria

1.Male or female, minimum age 18 years.
2.ECOG performance status of 0 to 2.
3.Adequate haematological function: haemoglobin > 9 g/dL, neutrophils count >1.5 × 109/L, platelet count > 100 × 109/L.
4.Adequate coagulation: INR = 1.5.
5.Adequate liver function: total bilirubin < 1.5 × ULN, ALT and/or AST < 2.5 × ULN, alkaline phosphatase < 5 ULN, except in the presence of exclusive bone metastases and in the absence of any liver disorder.
6.Adequate renal function: calculated creatinine clearance ¿ 50 mL/min (Cockroft-Gault) and proteinuria < 2+ (dipstick).
7.Oral swallowing capability, patient capable of proper therapeutic compliance, and accessible for correct follow-up.
8.Life expectancy of at least 3 months.
9.Women of childbearing age, including women who had their last menstrual period in the last 2 years, must have a negative serum or urine pregnancy test within 7 days before beginning treatment. Not eligible: women who are pregnant or in the period of lactation.
10.All sexually active men and women of childbearing age must use an effective contraceptive method during the study treatment and for a period of at least 12 months following the last administration of trial drugs. Not eligible: sexually active men and women of childbearing age who are not willing to use an effective contraceptive method during the study.
11. Written Informed Consent (IC) must be signed and dated by the patient and the investigator prior to any trial-related intervention for:
a)Trial treatment
b)Tissue submission to the reference laboratory
c)Blood/urine collection at baseline, every 8 weeks and at the time of progression
d)Eventual re-biopsy at progression
Disease characteristics
1.Pathological diagnosis of predominantly non-squamous, lung adenocarcinoma. Not eligible: patients with any other lung cancer subtype, patients with mixed NSCLC with predominantly squamous cell cancer, or with any small cell lung cancer (SCLC) component.
2.TNM version 7 stage IV disease including M1a (malignant effusion) or M1b (distant metastasis), or locally advanced disease not amenable to curative treatment (including patients progressing after radio-chemotherapy for stage III disease). Not eligible: patients who are candidates for radical surgery and/or radio(chemo)therapy with curative intention.
3.Measurable or evaluable disease (according to RECIST 1.1 criteria). Not eligible: patients with only one measurable or evaluable tumour lesion, which was resected or irradiated prior to enrolment.
4.Locally identified EGFR exon 19 deletion or exon 21 p.L858R.
5.Undergone a biopsy or surgical resection of either primary or clinically meaningful metastatic tumour tissue within 60 days of planned accrual to the trial and have tissue (histology and/or cytology) available to send to Department of Diagnostics and Public Health (Verona) or are able to undergo a biopsy during Screening and provide tissue to Department of Diagnostics and Public Health (Verona).
6.Patients with asymptomatic and stable cerebral metastases will be eligible for the study. Not eligible: patients with symptomatic or instable cerebral metastases requiring medical treatment.

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 27
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 27

Exclusion Criteria

1.Active second malignancy; i.e., patient known to have potentially fatal cancer present for which he/she may be (but not necessarily) currently receiving treatment.
2.Patients with a history of malignancy that has been completely treated, with no evidence of that cancer currently, are permitted to enrol in the trial provided all chemotherapy was completed > 6 months prior and/or bone marrow transplant > 2 years prior to first day of study treatment.
3.Past medical history of ILD, drug-induced ILD, radiation pneumonitis which required steroid treatment, or any evidence of clinically active ILD.
4.Patients with moderate to severe hepatic impairment (Child Pug B or C) due to cirrhosis.
5.Patients with active keratitis and severe ocular diseases.
6.Spinal cord compression, symptomatic and unstable brain metastases, requiring steroids over the last 4 weeks prior to enrollment in this study.
7.Refractory nausea and vomiting, chronic gastrointestinal diseases, inability to swallow the formulated product, or previous significant bowel resection that would preclude adequate absorption of gefitinib.
5.Non-study related surgical procedures less than or equal to 7 days prior to administration of study drug. In all cases, the patient must be sufficiently recovered and stable before treatment administration.
6.Females who are pregnant or breastfeeding.
7.Refusal to use adequate contraception for fertile patients (females and males) for 24 weeks after the last dose of gefitinib.
8. 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.
9.Any other reason the investigator considers the patient should not participate in the study.
Prior, recent or concurrent treatment
1.Prior treatment with cytotoxic chemotherapy for advanced NSCLC; neoadjuvant/adjuvant chemotherapy is permitted if at least 6 months has elapsed between the end of chemotherapy and enrollment
2.Patients who received previous treatment for lung cancer with drugs targeting EGFR.
3.Patients who received treatment with an investigational drug agent during the 3 weeks before enrolment in the study.
4.Treatment with prohibited medications less than or equal to14 days prior to first day of study treatment.

Study & Design

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