Radiation During Osimertinib Treatment: a Safety and Efficacy Cohort Study

NCT05089916 | Active Not Recruiting Phase 2 DMC

• 3 other identifiers: AIO-YMO/TRK-01202022-503028-29-012020-003512-27
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 1

Brief Summary

Study Objectives are: To assess the safety of osimertinib treatment continuation during irradiation therapy for palliation or oligoprogressive disease by assessment of grade 3-5 AEs during and after concomitant osimertinib and irradiation of tumor sites. To assess the efficacy of osimertinib treatment continuation during irradiation therapy for palliation or oligoprogressive disease. To investigate Quality of Life during and after irradiation therapy and concomitant osimertinib.

Conditions

NSCLC; Oligoprogression; EGFR Positive Non-small Cell Lung Cancer

Keywords

Osimertinib; Radiotherapy; TKI

Outcome Measures

Primary Outcomes (1)

• Frequency, time of onset and severity of Adverse Events as assessed by investigator during osimertinib treatment and irradiation therapy

  Safety and tolerability (Frequency, time of onset and severity of Adverse Events, grading according to CTCAE V5.0), including pneumonitis, interstitial lung disease, radiation pneumonitis, radionecrosis, radiation alveolitis, radiation fibrosis - lung, pulmonary radiation injury and cardiac failure (congestive heart failure - CHF) as adverse events of special interest

  24 months

Secondary Outcomes (5)

• PFS

  24 months

• TTF

  12 months

• Local tumor control

  24 months

• OS

  24 months

• QoL

  12 months

Other Outcomes (4)

• Blood sample analysis and biomarker assessment

  24 months

• Tissue-based biomarkers

  Before or within 3 weeks after start of study treatment

• Target volume of irradiation

  28 days

Study Arms (1)

Osimertinib plus Radiation

EXPERIMENTAL

Osimertinib 80 mg Radiation as per SOC

Drug: Osimertinib; Radiation: Radiotherapy

Interventions

Radiotherapy RADIATION

Radiotherapy: according to standard of care The target population will comprise 3 parallel cohorts, for cohort 1 and 3 a minimum of 10 subjects is planned to be enrolled: 1. Irradiation of bone, solid organ (non-lung, non-brain) or soft-tissue metastases 2. Irradiation of brain metastases (initial lesion size \< 3 cm) 3. Irradiation of lung lesions (primary tumor or metastases, lesion size \< 5 cm)

Osimertinib plus Radiation

Osimertinib DRUG

Osimertinib: according to its marketing authorization, i.e. at daily doses of 80 mg, for a maximum of 12 months within the study.

Also known as: Tagrisso

Osimertinib plus Radiation

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Provision of written informed consent prior to any study specific procedures, including screening evaluations that are not SOC.
• Age ≥ 18 years at time of study entry.
• Histologically confirmed NSCLC
• Ongoing or planned osimertinib treatment according to marketing authorization (first line treatment of tumor positive for a common or uncommon 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.)
• 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.
• ECOG performance status 0-2.
• Life expectancy ≥12 weeks
• 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 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
• Male subjects who are sexually active with WOCBP should be willing to use highly effective contraception. Men who are azoospermic do not require contraception.
• 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.
• Negative COVID-19 test within 1 week prior to starting irradiation if clinically required by current regional COVID-19 outbreak situation.

You may not qualify if:

• Concurrent enrolment in another clinical study, unless it is an observational (non-interventional) clinical study, or during the follow-up period of an interventional study.
• Treatment with an investigational drug within five half-lives of the compound or 3 months, whichever is greater
• Previous enrolment in the present study.
• 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 (e.g., hormone replacement therapy) is acceptable.
• Any unresolved toxicities from prior therapy greater than grade I (exception: alopecia, grade 2 neuropathy) which in the investigator's opinion would jeopardise compliance with the protocol or worsen during irradiation
• Cardiac side-effects of osimertinib not sufficiently improved by dose reduction as suggested by the label/ German "Fachinformation".
• In patients with indication for radiotherapy of lung lesions: past medical history of ILD/pneumonitis, radiation pneumonitis grade 2 or higher (CTCAE V5.0) or requiring steroid treatment, or any evidence of clinically active ILD, in particular interstitial pulmonary fibrosis (IPF).
• 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. Note: Local non-major surgery for palliative intent (e.g., surgery of isolated lesions) is acceptable.
• Congenital long QT syndrome
• Any of the following cardiac criteria:
• Mean resting corrected QT interval (QTc) \> 470 msec obtained from 3 electrocardiograms (ECGs), using the screening clinic ECG machine derived QTc value
• Any clinically important abnormalities in rhythm, conduction or morphology of resting ECG e.g. complete left bundle branch block, third degree heart block and second degree heart block.
• Patient with any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, electrolyte abnormalities (including: Serum/plasma potassium \< LLN; Serum/plasma magnesium \< LLN; Serum/plasma calcium \< LLN) , 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
• Inadequate bone marrow reserve or organ function (as demonstrated by any of the following laboratory values:
• Absolute neutrophil count \<1.5 x 109/L;

Sponsors & Collaborators

• AIO-Studien-gGmbH: lead
• AstraZeneca: collaborator

Study Sites (1)

LMU Klinikum der Universität München

München, 80336, Germany

Location

MeSH Terms

Interventions

osimertinib; Radiotherapy

Intervention Hierarchy (Ancestors)

Therapeutics

Study Officials

• Amanda Tufman, Prof. Dr.

  LMU Klinikum der Universität München

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Single arm, explorative, multi-center parallel cohort study

Study Record Dates

• First Submitted: April 13, 2021
• First Posted: October 22, 2021
• Study Start: January 20, 2022
• Primary Completion: March 1, 2026
• Study Completion (Estimated): March 1, 2027
• Last Updated: January 14, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)