A multicentre single-arm phase II trial assessing the safety and efficacy of first-line osimertinib and locally ablative radiotherapy in patients with synchronous oligo-metastatic EGFR-mutant non-small cell lung cancer

Phase 2

Withdrawn

• Conditions: lungcancer; Non small cell lung cancer; 10038667

• Registration Number: NL-OMON54434
• Lead Sponsor: ETOP IBCSG Partners Foundation

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Last Update Posted: 15 April 2024

Recruitment & Eligibility

• Status: Withdrawn
• Sex: Not specified
• Target Recruitment: 10

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

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
• Study Design: Not specified