临床试验/2024-513881-20-00

2024-513881-20-00招募中2 期

First-line treatment with osimertinib in EGFR-mutated non-small cell lung cancer, coupled to extensive translational studies (The FIOL-study)

Vestre Viken HF5 个研究点分布在 3 个国家目标入组 96 人开始时间: 2024年11月14日最近更新: 2024年11月28日

试验速览

阶段: 2 期
状态: 招募中
发起方
入组人数: 96
试验地点: 5
主要终点: To assess the efficacy of osimertinib by assessment of objective response rate (ORR).

研究概览入排标准结局指标研究者研究点记录与标识符相似试验

研究概览

简要总结

To assess the efficacy of osimertinib by assessment of objective response rate (ORR)

入排标准

年龄范围: 18 years 至 65+ years（65+ Years, 18-64 Years）
接受健康志愿者: 否

入选标准

•Provision of signed and dated, written informed consent.
•Age > 18 years.
•Histologically or cytologically documented locally advanced or metastatic NSCLC not amenable to curative surgery or radiotherapy. Patients that have received systemic adjuvant therapy for non-metastatic disease in the past will need a new biopsy before inclusion.
•Documented EGFR mutation in exon 18-21, except insertions in exon 20, based on tissue analysis
•ECOG status 0-2 and a minimum life expectancy of 12 weeks.
•Patients with untreated, mild or moderately symptomatic and measurable brain metastases are eligible, but will be allocated to cohort A (see excl. point 6). Patients with pre-treated, stable and asymptomatic brain metastases will be allocated to cohort B.
•At least one lesion, not previously irradiated and not chosen for biopsy during the study screening period, that can be accurately measured at baseline according to RECIST 1.
•Females should be using adequate contraceptive measures (see appendix E), 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 amenorrhoeic 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 amenorrhoeic for 12 months or more following cessation of exogenous hormonal treatments and with Luteinizing Hormone (LH) and Follicle-Stimulating Hormone (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.
•Male subjects must be willing to use barrier contraception

排除标准

•Previous systemic treatment against metastatic NSCLC.
•Past medical history of interstitial lung disease, drug-induced interstitial lung disease, radiation pneumonitis which required steroid treatment, or any evidence of clinically active interstitial lung disease.
•Inadequate bone marrow reserve or organ function (as demonstrated by any of the following laboratory values:  Absolute neutrophil count < 1.5 x 109/L  Platelet count < 100 x 109/L  Haemoglobin < 90 g/L  Alanine aminotransferase (ALT) > 2.5 times the upper limit of normal (ULN) if no demonstrable liver metastases or > 5 times ULN in the presence of liver metastases  Aspartate aminotransferase (AST) > 2.5 times ULN if no demonstrable liver metastases or > 5 times ULN in the presence of liver metastases  Total bilirubin > 1.5 times ULN if no liver metastases or > 3 times ULN in the presence of documented Gilbert’s Syndrome (unconjugated hyperbilirubinaemia) or liver metastases  Serum 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
•History of hypersensitivity of active or inactive excipients of osimertinib or drugs with a similar chemical structure or class to osimertinib.
•Treatment with an investigational drug within five half-lives of the compound or 3 months, whichever is greater.
•Previous enrolment in the present study or previous treatment with osimertinib.
•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.
•Women who are pregnant or breast-feeding, or have a positive (urine or serum) pregnancy test prior to study entry
•Involvement in the planning and/or conduct of the study (investigator staff and/or staff at the study site).
•Judgment by the investigator that the subject should not participate in the study if the subject is unlikely to comply with study procedures, restrictions and requirements.
•Major surgery within 4 weeks of inclusion
•Radiotherapy treatment to more than 30% of the bone marrow or with a wide field of radiation within 4 weeks of inclusion
•Subjects currently receiving (or unable to stop using) potent inducers of CYP3A
•Patients must stop using CYP3A4 inducers at least 3 weeks prior to treatment with osimertinib
•Subjects with spinal cord compression unless they have completed definitive therapy, are not on steroids and have had a stable neurological status for at least 2 weeks after completion of definitive therapy and steroids.
•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.
•Previous malignancy (except non-melanoma skin cancers, and the following in situ cancers: bladder, gastric, oesophageal, colon, endometrial, cervical, melanoma or breast) unless a complete remission was achieved at least 2 years prior to study entry.
•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.
•Exclude based on any of the following cardiac criteria:  Mean resting corrected QT interval (QTc) > 470 msec obtained from 3 electrocardiograms (ECGs), using the screening clinic ECG machine derived QTc value  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  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; serum/plasma calcium < LLN), 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

结局指标

主要结局

To assess the efficacy of osimertinib by assessment of objective response rate (ORR).

次要结局

To further assess the efficacy of osimertinib in terms of Progression free survival (PFS)
To further assess the efficacy of osimertinib in terms of Duration of Response (DoR)
To further assess the efficacy of osimertinib in terms of Disease Control Rate (DCR)
To further assess the efficacy of osimertinib in terms of Intracranial ORR
To further assess the efficacy of osimertinib in terms of intracranial DoR
To further assess the efficacy of osimertinib in terms of intracranial progression free survival (iPFS)
To further assess the efficacy of osimertinib in terms of tumour shrinkage
To further assess the efficacy of osimertinib in terms of overall survival (OS)
To confirm the safety profile of osimertinib
Exploratory objectives Molecular characterization of blood and tissue before commencement on osimertinib, and at progression on osimertinib
Exploratory objectives: NGS (deep sequencing) of tumour tissue
Exploratory objectives: Array-based microRNA, methylation, mRNA expression
Exploratory objectives : Immunohistochemistry (IHC) on AXL, cMET, CD73 etc
Exploratory objectives: Exploratory analyses to be determined
Mutational analyses (ctDNA) and conventional tumour markers during therapy

研究者

发起方

Vestre Viken HF

申办方类型

Hospital/Clinic/Other health care facility

责任方

Principal Investigator

主要研究者

Siri Bråthen

Scientific

Vestre Viken HF

研究点 (5)

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