First-Line Osimertinib for Poor Performance Status Patients with EGFR Mutant Non-Small Cell Lung Cancer

JRCT ID: jRCTs041200100

Registered date:12/02/2021

Basic Information

• Recruitment status: Not Recruiting
• Health condition(s) or Problem(s) studied: Non-small cell lung cancer
• Date of first enrollment: 16/02/2021
• Target sample size: 30
• Study type: Interventional
• Intervention(s): To administer orally 80 mg/day osimertinib once a day and continue until exacerbation or toxicity discontinuation targeting non-small cell lung cancer patients in poor general condition due to lung cancer (ECOG PS 2-4) with EGFR susceptibility gene mutation (EGFR Ex18 G719X, Ex19 DEL, Ex21 L858R, Ex21 L861Q) confirmed.

Outcome(s)

• Primary Outcome: Objective response rate

Secondary Outcome

Disease control rate [DCR]
Performance status [PS] improvement rate
Patient-reported outcome [PRO]: EORTC QLQ-C30 and LC13
Percentage of adverse events (AEs)
Percentage of weight loss and discontinuation due to toxicity

Key inclusion & exclusion criteria

• Age minimum: >= 20age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

1) Histologically or cytologically diagnosed as non-small cell lung cancer.
2) Confirmed tissue specimens or cytological specimens with EGFR-sensitive gene mutations (EGFR Ex18 G719X, Ex19 DEL, Ex21 L858R, Ex21 L861Q).
(In such mutation, compound mutations other than Ex20 insertion mutations are allowed.)
3) Clinical stage III/IV or postoperative recurrence in which definitive surgery and radiation are not possible (UICC-TNM classification 8th edition).
4) Age of 20 years or older at the time of consent.
5) ECOG PS 2-4 (PS decrease due to the underlying lung cancer judged by the attending doctor), and expected survival of 12 weeks or more.
6) Having measurable lesions based on Response Evaluation Criteria in Solid Tumor (RECIST) v1.1 (however, the site where irradiation was performed is not a measurable lesion).
7) Untreated cases of drug therapy for lung cancer including EGFR-TKI, immune checkpoint inhibitors, cytotoxic anticancer drugs. Preoperative and postoperative chemotherapy excluding EGFR-TKIs is acceptable if the final dose is at least 6 months prior to enrollment in this study.
8) No severe impairment in the major organ function, and the following criteria are met:
(Must be met within 14 days from the registration date. The same day of the week two weeks before the registration date is acceptable)
A) Number of neutrophils: 1,500/mm3 or more,
B) Hemoglobin: 9.0 g/dL or more,
C) Platelet count: 10.0 x 10,000/mm3 or more,
D) AST: 2.5 times or less of the upper limit of the institutional standard value (5 times or less if there is liver metastasis),
E) ALT: 2.5 times or less of the upper limit of the facility standard value (5 times or less if there is liver metastasis),
F) Total bilirubin: 1.5 times or less of the upper limit of the facility standard value (3 times or less if Gilbert's syndrome [non-conjugated hyperbilirubinemia] or liver metastasis is present),
G) Serum creatinine: 1.5 times or less of the facility standard value upper limit (however, if it exceeds 1.5 times the facility standard value upper limit, patients with creatinine clearance [measured value or value calculated by Cockcroft-Gault formula] of 50 ml/min or more are eligible), and
H) SpO2: 90% or more (with or without oxygen therapy, except for cases requiring positive pressure ventilation).
9) Written consent obtained from the patient after a sufficient explanation of the study content has been given prior to enrollment in this study.

Exclude criteria

1) Known EGFR Ex20 insertion mutation.
2) Having active double/multiple cancer (simultaneous double cancer/multiple cancer and metachronous double cancer/multiple cancer requiring treatment within 2 years of disease-free period). However, lesions equivalent to carcinoma in situ and intramucosal cancer that are judged to be cured by local treatment are not included in active double cancer/multiple cancer.
3) Interstitial lung disease, drug-induced interstitial lung disease, history of radiation pneumonia requiring steroid treatment, or active period interstitial lung disease.
4) Ingestion is not possible. Having a history of refractory nausea and vomiting, chronic gastrointestinal disorders, aphagia, or gastrointestinal resection that may significantly affect the absorption of osimertinib.
5) An active infection that requires systemic treatment (Active infections include all cases treated by intravenous administration for the infection).
6) Having difficulty in participation in the study because of clinically problematic psychosis or psychiatric symptoms.
7) Clinically unstable brain metastases.
8) Serious complications (severe or uncontrolled systemic disease including uncontrollable hypertension and active bleeding diathesis.)
9) Systemic administration of steroids for 4 weeks or longer. However, steroids within 20 mg/day in terms of prednisolone are acceptable.
10) PS decrease due to comorbidities including sequelae of cerebral infarction. However, for cases of coelomic fluid retention, cases for which this drug is administrable after drainage or adhesions can be registered.
11) At the time of enrollment, CTCAE grade 2 or higher toxicity due to systemic pretreatment including adjuvant chemotherapy continues, excluding alopecia and grade 2 neuropathy due to pretreatment chemotherapy.
12) One of the following treatments is being performed;
- underwent major surgery excluding blood vessel securing surgery within 4 weeks before registration,
- received more than 30% of bone marrow or extensive radiation therapy within 4 weeks prior to enrollment.
- patients who are taking drugs or herbal supplements known to have a strong inducing effect on Cytochrome P450 (CYP) 3A4 (or who cannot be discontinued at least 1 week before the first dose), and
- treatment with another investigational drug was received within 5 times the half-life of the compound, or 3 months, whichever is longer.
13) QT prolongation on resting electrocardiogram (Bazett's correction formula: QTc [= QT measured value/RR interval 1/2] exceeds 470 msec), clinically significant abnormalities in heart rate rhythm, conduction, and waveform (for example, complete left bundle branch block, 2nd to 3rd degree atrioventricular block, PR extension [more than 250 msec]).
14) QTc prolongation or Torsades de Pointes or factors that increase the risk of arrhythmia induction (heart failure, hypokalemia/hypokalemia/hypocalcemia and other electrolyte abnormalities, congenital long QT syndrome, cases with first-time relatives with a family history of long QT syndrome, cases with a family history of sudden death of unknown cause under the age of 40, cases using concomitant medications known to cause QT interval prolongation or Torsades de Pointes).
15) Having a history of hypersensitivity to the active ingredient or excipient of osimertinib, or a drug of the same chemical structure or class as osimertinib.
16) Pregnant women, lactating women, women with a positive pregnancy test, or no intention of contraception*.
17) In addition, the doctor in charge judged that it was inappropriate.
* To instruct proper contraception for a period of time (6 weeks for women who may become pregnant and 4 months for men whose partner may become pregnant) through and after the study drug administration.

Related Information

• Primary Sponsor: Katsuhiko Naoki
• Source(s) of Monetary Support: Thoracic Oncology Research Group