A clinical study exploring the effect of osimertinib and radiation therapy, in people with newly diagnosed non-small cell lung cancer (NSCLC) that has spread to a few other parts of the body and shows a change (mutation) in the EGFR gene.

Phase 1

Conditions: Treatment naïve patients with synchronous, oligo-metastatic (primary tumour and maximum 5 metastases) EGFR-mutant (exon 19 deletion or exon 21 L858R) NSCLC with or without T790M resistance mutation
MedDRA version: 21.1Level: PTClassification code 10029522Term: Non-small cell lung cancer stage IVSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Therapeutic area: Diseases [C] - Cancer [C04]
MedDRA version: 21.1Level: PTClassification code 10059515Term: Non-small cell lung cancer metastaticSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Registration Number: EUCTR2020-004114-35-NL

Lead Sponsor: ETOP IBCSG Partners Foundation

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 60

Inclusion Criteria

1) Histologically confirmed, treatment naïve EGFR-mutant NSCLC, with or without T790M resistance mutation.
2) Presence of sensitising EGFR-mutation (exon 19 deletion and/or exon 21 L858R) detected by an accredited laboratory.
3) Synchronous oligo-metastatic stage IV disease (max 5 lesions)
4) Measurable disease as defined according to RECIST v1.1
5) All lesions amenable for radical radiotherapy according to local judgment
6) ECOG performance status 0-2
7) Adequate haematological, renal and liver function
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 40
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 20

Exclusion Criteria

1) Prior chemotherapy, immunotherapy, radiotherapy or therapeutic surgery for NSCLC (an exception is the resection and postoperative radiotherapy of the resection cavity of CNS or adrenal metastases)
2) More than 5 distant oligo-metastases (any second intra-thoracic lesion will count as a distant metastasis; regional nodal metastases will not count towards the 5 oligometastases) and more than 2 intra-pulmonary lesions.
3) Brain metastases not amenable for radiosurgery or neurosurgery
4) Presence of leptomeningeal metastases
5) Symptomatic spinal cord compression
6) Extracranial metastatic locations not amenable for radical radiotherapy such as malignant ascites, pleural or pericardial effusion, diffuse lymphangiosis of skin or lung, diffuse bone marrow metastasis, metastasis invading the GI tract, abdominal masses/abdominal organomegaly, identified by physical exam that is not measurable by reproducible imaging techniques
7) Currently receiving, or unable to stop use prior to enrolment or to receiving the first dose of osimertinib treatment, medications or herbal supplements known to be potent CYP3A4 inducers. Potent CYP3A4 inducers are contraindicated for the duration of the trial.
8) 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.
Patients 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
- Positive for HBsAg, negative for HBeAg but for >6 months have had transaminases levels below ULN and HBV DNA levels below 2000 IU/mL (i.e., are in an inactive carrier state).
9) 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
10) Any of the following cardiac criteria:
- QTcF >470 msec, using the screening clinic ECG machine derived QTc value (QTcF: corrected QT interval using Fredericia's formula).
- Any clinically important abnormalities in rhythm, conduction or morphology of resting ECG (e.g., complete left bundle branch block, third degree heart block or
second degree heart block).
- Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, hypokalaemia, 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 (TdP).
11) Past medical history of ILD, drug induced ILD, radiation pneumonitis which required steroid treatment, or any evidence of clinically active ILD
12) Idiopathic pulmonary fibrosis which is a contraindication to lung radiation
13) History of hypersensitivity to active or inactive excipients of osimertinib or drugs with a similar chemical structure or class to osimertinib

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method

Secondary Outcome Measures

Name	Time	Method

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