Radiation during Osimertinib Treatment: a Safety and Efficacy Cohort Study

Phase 1

• Conditions: Patients with EGFR-mutation positive NSCLCThe target population will comprise 3 parallel cohorts, for each of which a minimum of 10 subjects is planned to be enrolled:1. Irradiation of bone, solid organ (non-lung, non-brain) or soft-tissue metastases2. Irradiation of brain metastases (initial lesion size < 3 cm)3. Irradiation of lung lesions (primary tumor or metastases, lesion size < 5 cm); MedDRA version: 20.0Level: LLTClassification code 10025064Term: Lung carcinomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 20.0Level: LLTClassification code 10007096Term: Cancer of lungSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 21.1Level: PTClassification code 10061873Term: Non-small cell lung cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); 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]

• Registration Number: EUCTR2020-003512-27-DE
• Lead Sponsor: AIO-Studien-gGmbH

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2021-08-11
• Last Update Posted: 26 August 2024

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 40

Inclusion Criteria

1. Provision of written informed consent prior to any study specific procedures, including screening evaluations that are not SOC.
2. Age = 18 years at time of study entry.
3. Histologically confirmed NSCLC
4. Ongoing or planned osimertinib treatment according to marketing authorization (first line treatment of tumor positive for an activating EGFR mutation, or later line treatment of tumor positive for EGFR T790M mutation, assessed according to local standard. First line therapy is defined as therapy used to treat advanced disease. Each subsequent line of therapy is preceded by disease progression. A switch of an agent within a regimen in order to manage toxicity does not define the start of a new line of therapy. Experimental therapies when given as separate regimen are considered as separate line of therapy. Maintenance therapy following platinum doublet-based chemotherapy is not considered as a separate regimen of therapy.)
5. Clinical indication for radiotherapy of one or more lesions, for instance for local symptom control of primary tumor or metastasis, for oligoprogressive metastasis, or for disease control with conventional or stereotactic strategy. Radiotherapy of metastatic sites can be for bone, solid organ or soft-tissue lesions; initial size of brain metastases should be < 3 cm. Lung lesions should be no more than 5 cm.
6. ECOG performance status 0-2.
7. Life expectancy =12 weeks
8. Female subjects should be using highly effective contraceptive measures, and must have a negative pregnancy test and not be breast-feeding 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 sterilisation by hysterectomy, bilateral oophorectomy or bilateral salpingectomy but not tubal ligation
• Further information in Section 7.1.1 and Appendix 21.7
9. Male subjects who are sexually active with WOCBP should be willing to use highly effective contraception (see Section 7.1.1 and Appendix 21.7). Men who are azoospermic do not require contraception.
10. The patient is willing and able to comply with the protocol for the duration of the study, including hospital visits for treatment and scheduled follow-up visits and examinations.
11. Negative COVID-19 test within 1 week prior to starting irradiation if clinically required by current regional COVID-19 outbreak situation.
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 30
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 30

Exclusion Criteria

1. Concurrent enrolment in another clinical study, except observational clinical study, or during the FU of an interventional study
2. Treatment with an investigational drug within 5 half-lives of the compound or 3 months, whichever is greater
3. Previous enrolment in the present study
4. Any chemotherapy, biologic or hormonal cancer therapy other than EGFR-TKIs used concurrently or within 4 weeks prior to study enrolment, or checkpoint inhibitors within 130 days prior to study enrolment. Hormonal therapy for non-cancer-related conditions is acceptable
5. Any unresolved toxicities from prior therapy greater than grade I which in the investigator’s opinion would jeopardise compliance with the protocol or worsen during irradiation
6. Cardiac side-effects of osimertinib not sufficiently improved by dose reduction as suggested by the label/ Fachinformation
7. In patients with indication for radiotherapy of lung lesions: past medical history of ILD/pneumonitis, radiation pneumonitis grade 2 or greater (CTCAE V5.0) or requiring steroid treatment, or any evidence of clinically active ILD, in particular IPF
8. Major surgery (as defined by the Investigator) within 4 weeks prior to starting the study; patients must have recovered from effects of preceding major surgery.
9. Congenital long QT syndrome
10. Any of the following cardiac criteria: Mean resting QTc >470 msec obtained from 3 ECGs, using the screening clinic ECG machine derived QTc value; Any clinically important abnormalities in rhythm, conduction or morphology of resting ECG; Patient with any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, electrolyte abnormalities
11. Inadequate bone marrow reserve or organ function as demonstrated by any of the following laboratory values: Absolute neutrophil count <1.5 x 10^9/L; Platelet count <100 x 10^9/L; Hb <90 g/L (9 g/dL); ALT >2.5 times >5 times ULN nin absence or presence of liver metastases resp.; AST >2.5 times or >5 times ULN in absence and presence of liver metastases resp.; Total bilirubin >1.5 times ULN if no liver metastases or >3 times ULN in the presence of documented Gilbert’s Syndrome/liver metastases; Serum creatinine >1.5 times ULN concurrent with creatinine clearance <50 mL/min —confirmation of creatinine clearance is only required when creatinine is >1.5 times ULN
12. Any evidence of severe or uncontrolled systemic diseases, also uncontrolled hypertension & active bleeding diatheses, which according to the investigator makes the patient undesirable, or active infection
13. Past medical history of interstitial lung disease, drug-induced interstitial lung disease, radiation pneumonitis which required steroid treatment, or any evidence of clinically active interstitial lung disease
14. History of hypersensitivity to active or inactive excipients of osimertinib or drugs with a similar chemical structure or class to osimertinib.
15. Judgment by the investigator that the patient should not participate in the study if the patient is unlikely to comply with study procedures, restrictions and requirements
16. Active infection will include any patients receiving treatment for infection
17. Clinical suspicion of COVID-19
18. Participants with HBV infection are eligible only if they demonstrated absence of HCV co-infection or history of HCV co-infection and absence of HIV infection
Participants with active HBV infection are eligible if they are receiving anti-viral treatment for a

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified