NIPH Clinical Trials Search

Randomized Phase II Study of Osimertinib +- Chemotherapy in Relapsed EGFR-Mutant NSCLC After Adjuvant Osimertinib (WJOG17523L:ORACLE study)

Basic Information

Recruitment status	Recruiting
Health condition(s) or Problem(s) studied	Non-small cell lung cancer (NSCLC) with EGFR-sensitive mutations (Ex19del or L858R)
Date of first enrollment	24/04/2026
Target sample size	86
Countries of recruitment
Study type	Interventional
Intervention(s)	-Standard treatment arm-Osimertinib Osimertinib is administered orally at a dose of 80 mg once daily starting on Day 1. Osimertinib is continued until disease progression or the occurrence of unacceptable toxicity. -Investigational treatment arm-Osimertinib + platinum + pemetrexed Osimertinib is administered orally at a dose of 80 mg once daily starting on Day 1. In addition, cisplatin (75 mg/m2) or carboplatin (AUC 5) is administered intravenously, and pemetrexed (500 mg/m2) is administered intravenously. The platinum agent and pemetrexed are administered once every 3 weeks for 4 cycles as induction therapy. After completion of 4 cycles, in the absence of disease progression, maintenance therapy with pemetrexed monotherapy is administered once every 3 weeks and continued until disease progression or the occurrence of unacceptable toxicity. Osimertinib is continued throughout until disease progression or the occurrence of unacceptable toxicity.

Outcome(s)

Primary Outcome

Progression-Free Survival (PFS) (assessed by central review:BICR)

Secondary Outcome

Objective Response Rate (ORR) assessed by central review (in patients with measurable lesions only) All the following will be assessed by the investigator: Progression-Free Survival (PFS) (Investigator-assessed PFS) Disease Control Rate (DCR) Overall Survival (OS) Time to Treatment Failure (TTF) Time to Treatment Failure 2 (TTF2) Progression-Free Survival 2 (PFS2): time from randomization to progression on the subsequent line of therapy Safety

Key inclusion & exclusion criteria

Age minimum	> 18age old
Age maximum	Not applicable
Gender	Both
Include criteria	[Informed Consent & Age] 1) Patients must have provided written informed consent after receiving a full explanation of the study before enrollment. 2) Patients must be 18 years or older at the time of consent. 3) Patients must be able to provide the necessary blood samples required for biomarker analysis in this study. [Histological Type & Biomarkers] 4).Patients must have histologically or cytologically confirmed non-squamous NSCLC. Combined small-cell lung cancer (SCLC) components are not eligible. 5).Patients must have EGFR-sensitive mutations (Exon 19 deletion or Exon 21 L858R) confirmed by tissue or cytology-based testing. The testing method is not restricted if it is approved under Japanese health insurance regulations. Patients with concurrent exon 19 deletion and L858R, or those with other uncommon EGFR mutations, are not eligible for enrollment. [Prior Treatment, Disease Extent, and Severity] 6).The patient has undergone complete anatomical resection (segmentectomy or lobectomy or pneumonectomy) and has a postoperative pathological stage II-III non-small cell non-squamous lung cancer (according to UICC TNM Classification, 9th edition). The patient received adjuvant osimertinib monotherapy for >=24 months from the start to the end of treatment. Dose reduction during the adjuvant period is acceptable (Even in such cases, the dose of osimertinib at the start of the current study treatment is 80 mg.). The duration of therapy is defined as the period from the first to the last administration date, excluding any treatment interruptions. 7).Patients must have radiologically confirmed recurrence at least 3 months after discontinuing adjuvant osimertinib. 8).Patients must not have received any systemic therapy for recurrent disease and must be deemed eligible for systemic drug therapy by their treating physician. Osimertinib in this study must be initiated at a dose of 80 mg daily. The presence of measurable lesions is not required. For patients who underwent local therapy after recurrence, the date of the first recurrence will be considered the recurrence date. If disease progression is later confirmed at another site after local therapy, and the treating physician determines that systemic therapy is warranted, the patient remains eligible for enrollment. Any lesion previously treated with local therapy (e.g., radiation) will not be considered a measurable lesion. [General Condition and Laboratory Criteria] 9).ECOG Performance Status (PS) must be 0-1. 10).Patients must have an expected survival of at least 12 weeks. 11).Patients must not have symptomatic brain metastases. 12).The patient does not have leptomeningeal disease. 13).Patients must meet the following minimum washout periods before enrollment (same-day enrollment is allowed if the corresponding weekday has passed): -surgery (including resection of metastatic lesions) 4 weeks -Thoracoscopic pleural biopsy, exploratory thoracoscopy, surgical exploratory thoracotomy, exploratory laparotomy, palliative radiation for metastatic lesions 2 weeks -Radiation therapy including lung 4 weeks -Gamma Knife or stereotactic radiation for metastases 1 week -Thoracic drainage for malignant pleural effusion 2 weeks -Pleurodesis or Pericardial sclerosis 2 weeks -Blood transfusion, administration of hematopoietic growth factors 1 week Bisphosphonate therapy or anti-Receptor Activator of Nuclear Factor Kappa Beta Ligand (RANKL) antibody therapy is allowed if required for the management of hypercalcemia or prevention of skeletal events. 14). Patients must not have severe dysfunction of major organs and must meet the following laboratory and clinical criteria based on data obtained within 14 days prior to enrollment (same-day enrollment is allowed if the corresponding weekday has passed): Absolute neutrophil count (ANC): >= 1,500 / mm3 Hemoglobin: >= 9.0 g/dL Platelet count:>= 10.0*104 /mm3 Aspartate aminotransferase (AST): <= 100 IU/L Alanine aminotransferase (ALT): <= 100 IU/L Total bilirubin: <= 1.5 mg/dL Creatinine clearance: >= 45 mL/min Oxygen saturation (SpO2):>= 93% on room air Electrocardiogram (ECG):Corrected QT interval (QTc) <= 470 msec at rest, and no clinically significant abnormalities, such as third-degree atrioventricular (AV) block or second-degree AV block. Creatinine Clearance will be calculated using the Cockcroft-Gault formula, with actual body weight applied in the calculation. 15). Patients must not have experienced any of the following serious adverse events related to prior osimertinib monotherapy, as defined below: -Interstitial lung disease (ILD), regardless of grade -QTc prolongation accompanied by signs or symptoms of serious arrhythmia -Erythema multiforme or Stevens-Johnson syndrome -Any other grade >=3 adverse event related to osimertinib that does not resolve to grade <=2 within 3 weeks after discontinuation of the drug 16) Females must be using highly effective contraceptive measures, 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: -Post-menopausal defined as aged 50 years or more and amenorrheic 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 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 -Documentation of irreversible surgical sterilization by hysterectomy, bilateral oophorectomy or bilateral salpingectomy but not tubal ligation.
Exclude criteria	Patients who meet any of the following criteria will be excluded from the study: 1)Patients with active multiple primary malignancies. Definition: Multiple malignancies include synchronous malignancies and metachronous malignancies diagnosed within 3 years of disease-free status. However, carcinoma in situ (CIS) or mucosal carcinoma that has been treated with local therapy and is considered cured will not be classified as an active multiple malignancy. 2) Patient with any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as electrolyte abnormalities including: Hypokalemia| >= CTCAE Grade 2, heart failure, 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 Torsade de Pointes. Correction of electrolyte abnormalities should be documented prior to first dose. 3)Patients currently receiving (or unable to stop use prior to receiving the first dose of study treatment) medications or herbal supplements known to be strong inducers of CYP3A4 (at least 3-week prior) (Appendix X). All patients must try to avoid concomitant use of any medications, herbal supplements and/or ingestion of foods with known inducer effects on CYP3A4. 4)Patients with any evidence of severe or uncontrolled systemic diseases, including uncontrolled hypertension and active bleeding diatheses, which in the investigators opinion makes it undesirable for the patient to participate in the trial or which would jeopardise compliance with the protocol, or active infection (e.g. patients receiving treatment for infection) including hepatitis C and human immunodeficiency virus (HIV), or active uncontrolled HBV infection. 5)Patients with clinically significant psychiatric disorders that may interfere with study participation. as judged by the investigator. 6).Patients requiring continuous systemic steroid therapy (oral or intravenous) at doses higher than. 10 mg/day of prednisolone equivalent (excluding endocrine or autoimmune disease-related cases), or those currently receiving immunosuppressive agents. 7).Patients with a history of hypersensitivity to any component or excipient of osimertinib, cisplatin, carboplatin, or pemetrexed. 8).Patients currently participating in another clinical trial involving investigational drugs or devices, or who have completed such a trial within 4 weeks before enrollment. Concurrent participation in other trial procedures during this study is not permitted. 9).Patients with unresolved toxicities from prior treatment exceeding CTCAE Grade 1 at the time. of enrollment. Alopecia and Grade 2 platinum-based peripheral neuropathy are acceptable. Toxicities related to osimertinib are allowed if they meet the criteria in Section 5.1. 10).Patients who are judged by the investigator to be unlikely to comply with the study procedures, restrictions, and requirements. 11).Patients deemed inappropriate for study participation by the investigator for any other reason. 12).Patients with any of the following complications: (a)Interstitial Lung Disease (ILD) and Autoimmune Diseases -Patients with clear evidence of interstitial lung disease (ILD) on CT are excluded. -However, radiation-induced pneumonitis is allowed if symptoms are stable and systemic steroid treatment has not been required for >=3 months. -Patients whose adjuvant osimertinib was discontinued due to drug-induced pneumonitis are not eligible. (b) Viral Hepatitis -Patients positive for HBsAg or anti-HCV antibodies are excluded. -HBsAg-negative and anti-HBs-positive patients may be included. 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 <100 IU/mL 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. or -Positive for HBsAg, but for > 6 months have had transaminases levels below ULN and HBV DNA levels below <100 IU/mL (i.e., are in an inactive carrier state). In addition, patients must be receiving anti-viral prophylaxis for 2-4 weeks prior to study treatment. (c) Gastrointestinal Disorders -Patients with intractable nausea/vomiting, chronic gastrointestinal disease, total gastrectomy, dysphagia, or a history of major bowel resection that could impair absorption of osimertinib. (d)HIV 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/uL -No history of AIDS-defining opportunistic infection within the past 12 months -Stable for at least 4 weeks on the same anti-HIV medications