A phase II study of consolidative radiotherapy for residual lesions during osimertinib monotherapy (ORIHALCON trial/WJOG13920L)

JRCT ID: jRCTs041220115

Registered date:27/12/2022

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: Non-small cell lung cancer
• Date of first enrollment: 18/01/2023
• Target sample size: 76
• Study type: Interventional

Intervention(s)

<Standard therapy group>
Osimertinib monotherapy

<Study treatment group>
Osimertinib monotherapy + consolidation radiation therapy for residual disease

Outcome(s)

• Primary Outcome: Progression free survival
• Secondary Outcome: Safety, 1-year progression-free survival rate, duration of treatment, overall survival, number of residual disease organs and residual disease units in relation to efficacy

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

1) Patients are at least 18 years of age at the time consent is obtained.
2) Written consent has been obtained from the patient himself/herself after a thorough explanation of the study details has been provided prior to enrollment in the study.
3) Patients with histologically or cytologically diagnosed non-small cell lung cancer.
4) Patients with a diagnosis of clinical stage IVA/IVB or postoperative recurrence.
5) Patients with a confirmed EGFR susceptibility gene mutation (exon19 deletion or exon21 L858R) in a tissue or cytology specimen (any method of measurement is acceptable as long as the method is approved by insurance in Japan). In addition to the above mutations, patients with concomitant EGFR uncommon mutations are also acceptable. However, the coexistence of exon19 deletion and exon21 L858R is ineligible.
6) Patients who have received osimertinib monotherapy as initial therapy and have confirmed PR or SD (evaluated according to RECIST ver. 1.1). Confirmation of best response is not required. However, SD must be confirmed by efficacy assessment at least 6 weeks after the baseline assessment).
7) Patients receiving osimertinib at 80 mg/day or 40 mg/day daily (dose reduction to every other day or less is not allowed).
8) Patients who have received osimertinib monotherapy for at least 90 days but not more than 120 days at the time of enrollment after initiation of first-line osimertinib monotherapy.
9) Perioperative chemotherapy in patients with postoperative recurrence is acceptable for enrollment even if perioperative chemotherapy is administered without EGFR-TKI.
10) Patients with residual disease at the time of enrollment based on the following definitions, with a total of 3 or fewer residual lesions.
Extracranial tumor lesions: lesions with a long diameter of 10 mm or more on CT with a slice thickness of 5 mm or less.
Extracranial lymph node lesions: lesions with a short diameter of 10 mm or more on CT with a slice thickness of 5 mm or less.
Intracranial lesions: lesions with a long diameter of 10 mm or greater on MRI with a slice thickness of 5 mm or less.
However, lesions for which radiotherapy has already been performed prior to registration are not treated as residual lesions even if they meet the above definition.
11) Patients who are judged to be eligible for radiotherapy for all residual lesions defined in 10).
12) Patients with an ECOG PS of 0 or 1.
13) Patients without severe impairment of major organs.
14) Patients who have not experienced any serious adverse events with osimertinib monotherapy.
15) Expected to survive at least 3 months from enrollment.

Exclude criteria

1) Patients with active overlapping cancers.
2) Patients with poorly controlled malignant pleural, pericardial, or ascites effusions.
3) Patients with symptomatic brain metastases.
4) Patients with local infections or active systemic infections requiring treatment.
5) Patients with active hepatitis B, active hepatitis C with treatment or active human immunodeficiency virus (HIV) infection.
6) Males who are unwilling to use contraception. 6) Pregnant or lactating women, women who have had a positive pregnancy test or who are unwilling to use contraception.
7) Patients with clinically problematic psychiatric disorders that would preclude enrollment in the study.
8) Patients with interstitial lung disease, drug-induced interstitial lung disease, idiopathic pulmonary fibrosis, history of radiation pneumonitis requiring steroid therapy, or active periodic interstitial lung disease.
9) Patients with refractory nausea and vomiting, chronic gastrointestinal disease, dysphagia of preparations, total gastrectomy, or a history of significant bowel resection that would preclude adequate absorption of osimertinib.
10) Patients with heart failure, hypokalemia, congenital QT prolongation syndrome, a family history of QT prolongation syndrome, or a family history of unexplained sudden death in the first degree (parent and child) at age less than 40 years, known to prolong the QT interval and induce torsades de pointes (TdP) Cases in which concomitant medications are used.
11) Patients with other severe or poorly controlled systemic diseases, including uncontrolled hypertension and predisposition to active bleeding, that are deemed by the treating physician to make participation in the study undesirable.
12) Patients with a history of hypersensitivity to the active ingredient or inactive excipients of osimertinib or to drugs of similar chemical structure or class to osimertinib.
13) Patients who have received treatment with any investigational drug within approximately five times the half-life of the study drug or within three months, whichever is longer.
14) Patients taking concomitant medications or herbal supplements known to be potent inducers of CYP3A4.
15) Patients who have not yet recovered from the toxic effects of previous treatment for lung cancer.
16) Patients who, in the judgment of the treating physician, are unlikely to comply with the study procedures, limitations and requirements.
17) Other patients deemed by the treating physician to be unsuitable.

Related Information

• Primary Sponsor: Kenmotsu Hirotsugu
• Secondary Sponsor: Shikama Naoto,Oshima Masaki
• Source(s) of Monetary Support: AstraZeneca K.K.