NEJ067

JRCT ID: jRCTs011240066

Registered date:20/01/2025

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: Non-Small Cell Lung Cancer
• Date of first enrollment: 20/01/2025
• Target sample size: 40
• Study type: Interventional
• Intervention(s): Oshimertinib 80mg/day with cisplatin 75mg/m2 or carboplatin AUC 5 plus pemetrexed 500mg/m2 every3week are administred up to 4cycles,followed by osimertinib 80mg/day and pemetrexed 500mg/m2 every 3week till the discontinuation criteria such as progression(PD).

Outcome(s)

• Primary Outcome: Objective Response Rate
• Secondary Outcome: Safety, Progression-Free Survival, Overall Survival, PFS and OS in patients with/without central nervous system metastases at the start of treatment, and PFS, OS, ORR according to mutation type (single mutation or compound mutation)

Key inclusion & exclusion criteria

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

Include criteria

(1) Non-squamous cell NSCLC confirmed using histology or cytology.
(2) Cases of clinical stage IIIB, IIIC, IVA, or IVB* or postoperative recurrence in which surgery and radical irradiation are impossible.
*General rules for clinical and pathological records of lung cancer (January 2017 [8th edition]) Edited by The Japan Lung Cancer Society
(3) Patients harboring uncommon EGFR mutation (other than exon 19 deletion/exon 21 L858R mutation/exon 20 insertion. Patients with compound mutations may be enrolled if one or more uncommon mutations are present.
* EGFR mutation should diagnosed using test methods that are covered by insurance in Japan.
* Sensitive uncommon mutation is defined as a mutation in the exon 18-21 part of the EGFR kinase domain, excluding exon 19 deletion and exon 21 L858R.
(4) Patients with measurable lesions based on RECIST version 1.1.
(5) Patients without a history of chemotherapy using cytotoxic anticancer drugs, drugs with EGFR-inhibiting effects, and immune checkpoint inhibitors for NSCLC.
*Preoperative and postoperative adjuvant chemotherapy, except for drugs with EGFR-inhibiting effects, will be accepted if 6 months have passed since the last administration.
*Pleurodesis will be accepted.
(6) Patients aged >= 20 years at the time of informed consent.
(7) Patients with an Eastern Cooperative Oncology Group performance status (PS) of 0-1.
(8) Patients who meet the following criteria for major organ function within 14 days before registration (The same day of the week, that is, 2 weeks before the day of registration, is acceptable.
If more than one examination result exists within the applicable period, the result closest to the day of registration will be adopted. Blood transfusion and administration of hematopoietic factor preparations will not be conducted 14 days before the day of examination.):
1) Absolute neutrophil count >= 1.5 x109/L
2) Hemoglobin: >= 9.0 g/dL
3) Platelet count: >= 100 x 109/L
4) Aspartate aminotransferase (AST): <=2.5 times the upper limit of the institutional standard value (<=5 times if liver metastasis is present)
5) Alanine aminotransferase (ALT): <=2.5 times the upper limit of the institutional standard value (<= 5 times if liver metastasis is present)
6) Total bilirubin: <= 1.5 times the upper limit of the institutional standard value (<= 3 times if liver metastasis or Gilbert disease is present)
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.
8)SpO2: >= 95%
9) Left ventricular ejection fraction: >=55%
(9) Patients who have received a thorough explanation of the contents of the study and have provided written informed consent.

Exclude criteria

(1) 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 neuropathy due to perioperative chemotherapy.
(2) Patients with a history of interstitial lung disease (ILD), drug-induced ILD, or radiation pneumonitis requiring steroid therapy or patients with active ILD.
(3) Patients with clinically unstable brain metastases or spinal cord compression.
(However, patients will be eligible if they are not on steroids and have a stable neurological status for at least 2 weeks after the completion of definitive therapy and steroids.)
(4) Patients who have received radiation for the primary lesion and the lesion for evaluation.
*Patients who received radiation for metastatic lesions in the brain or bone not < 2 weeks prior will not be excluded.
(5) Patients with serious complications (such as poorly controlled heart, lung, liver, or kidney disease).
(6) Patients meeting any of the following criteria:
1) Patients with resting corrected QT interval (QTc) exceeding 470 ms
2) Patients showing any clinically important abnormalities in rhythm, conduction, or morphology of the resting electrocardiogram (ECG), for example, complete left bundle branch block, third-degree heart block, or second-degree heart block.
3) Patients with any factors that increase the risk of QTc prolongation or risk of arrhythmic events, such as electrolyte abnormalities, including the following:
-Serum/plasma potassium <= LLN
-Serum/plasma magnesium <= LLN
-Serum/plasma calcium <= LLN
-Heart failure, hypokalemia, congenital long QT syndrome, family history of long QT syndrome, or unexplained sudden death in first-degree relatives under 40 years of age or any concomitant medication known to prolong the QT interval and cause Torsades de Pointes (TdP)
(7) Patients with concomitant active hepatitis B*, hepatitis C, or human immunodeficiency virus infection.
*Patients with HBV are only eligible for inclusion if they meet all the following criteria:
-Demonstrated absence of HCV co-infection or history of HCV co-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, HBV DNA is suppressed to (< 10 IU/mL or under the limit of detection per local lab standard)
and transaminase levels are below ULN.
Participants with a resolved or chronic HBV infection are eligible if they are:
Negative for HBsAg and positive for hepatitis B core antibody (anti-HBc IgG or total anti-HBc Ab). In addition, patients must be receiving anti-viral prophylaxis for 2-4 weeks prior to study treatment if HBV DNA > 20 IU/mL.
or
Positive for HBsAg, but have had transaminases levels below ULN and HBV DNA levels < 10 IU/mL or under the limit of detection per local lab standard (i.e., are in an inactive carrier state) for > 6 months. In addition, patients must be receiving anti-viral prophylaxis for 2-4 weeks prior to study treatment.
Patients with HIV are only eligible for inclusion if they meet all the following criteria:
-Demonstrated absence of HBV/ HCV co-infection
-Undetectable viral RNA load for 6 months
-CD4+ count of >350 cells/micro L
-No history of AIDS-defining opportunistic infection within the past 12 months
-Stable for at least 4 weeks on the same anti-HIV medications
(8) Men without the intention to use contraception measures, pregnant women, lactating women, women who are positive for pregnancy tests, and women who do not intend to use contraception.*
* The following female patients will be enrolled:
-Female patients aged > 50 years and amenorrheic for at least 12 months following cessation of all exogenous hormonal treatments
-Women aged < 50 years will be considered postmenopausal if they have been amenorrheic for >= 12 months following cessation of exogenous hormonal treatments and with luteinizing hormone and follicle stimulating hormone levels in the post-menopausal range for the institution.
-Documentation of irreversible surgical sterilization by hysterectomy, bilateral oophorectomy, or bilateral salpingectomy but not by tubal ligation.
(9)Patients with refractory nausea and vomiting, chronic gastrointestinal diseases, inability to swallow the formulated product, total gastrectomy, or previous significant bowel resection that would preclude adequate absorption of osimertinib.
(10)Patients with pleural effusion, pericardial effusion, or ascites retention requiring drainage.
*Patients whose symptoms stabilize after drainage may be registered.
(11)Patients in whom osimertinib, cisplatin, carboplatin, and pemetrexed are contraindicated.
(12)Patients with synchronous double cancer or metachronous double cancer with the disease-free period of <= 3 years.
*Patients with carcinoma in situ or intramucosal cancer who are judged to be cured by topical treatment will not be excluded.
(13) Patients who are incapable of oral ingestion.
(14) Patients with a life expectancy <= 12 weeks.
(15)Involvement in the planning and/or conduct of the study (applied to both the investigator and staff at the study site).
(16)Treatment with an investigational drug within five half-lives of the compound or 3 months, whichever is longer
(17)Currently receiving (or unable to stop use before receiving the first dose of study treatment) medications or herbal supplements known to be strong inducers of CYP3A4 (at least 3 weeks prior).
(18) Patients with known hypersensitivity to any of the active or inactive excipients of study drugs (osimertinib, cisplatin, carboplatin, and pemetrexed) or related compounds.
(19)Any evidence of severe or uncontrolled systemic diseases, including uncontrolled hypertension and active bleeding diathesis, which in theinvestigator's opinion makes it undesirable for the patient to participate in the trial or jeopardizes compliance with the protocol.
(20) Other patients deemed ineligible for participation by the investigator or subinvestigators.

Related Information

• Primary Sponsor: Asahina Hajime
• Secondary Sponsor: Nonprofit Organization, North East Japan Study Group