Osimertinib for Non-small cell lung cancer | Non-small cell lung cancer stage IV

Inclusion criteria

• {"criterion_text":"- Provision of written informed consent prior to any study specific procedures, including screening evaluations that are not SOC.\n- 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.\n- Negative COVID-19 test within 1 week prior to starting irradiation if clinically required by current regional COVID-19 outbreak situation.\n- Age ≥ 18 years at time of study entry.\n- Histologically confirmed NSCLC\n- 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.)\n- 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.\n- ECOG performance status 0-2\n- Life expectancy ≥12 weeks\n- 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\n- Male subjects who are sexually active with WOCBP should be willing to use highly effective contraception. Men who are azoospermic do not require contraception."}

Exclusion criteria

• {"criterion_text":"- Concurrent enrolment in another clinical study, unless it is an observational (noninterventional) clinical study, or during the follow-up period of an interventional study.\n- 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\n- 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\n- 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\n- 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\n- History of hypersensitivity to active or inactive excipients of osimertinib or drugs with a similar chemical structure or class to osimertinib.\n- 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\n- Active infection will include any patients receiving treatment for infection\n- Clinical suspicion of COVID-19\n- 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 at least 6 weeks prior to study treatment, HBV DNA is suppressed to <100 IU/mL and transaminase levels are below ULN. Participants with a resolved or chronic HBV infection are eligible if they are negative for HBsAg and positive for hepatitis B core antibody [antiHBc IgG]. In addition, patients must be receiving anti-viral prophylaxis for 2-4 weeks prior to study treatment or Positive for HBsAg, but for > 6 months have had transaminases levels below ULN and HBV DNA levels <100 IU/mL. In addition, patients must be receiving anti-viral prophylaxis for 2-4 weeks prior to study treatment. Participants with HIV infection are only eligible if they have undetectable viral RNA load for 6 months, CD4+ count of >350 cells/μL, No history of AIDS-defining opportunistic infection within the past 12 months and Stable for at least 4 weeks on the same anti-HIV medications.\n- Treatment with an investigational drug within 5 half-lives of the compound or 3 months, whichever is greater\n- Currently receiving medications or herbal that are strong inducers of CYP3A4 (at least 3 week prior)\n- Women who are pregnant or breast-feeding\n- Male or female patients of reproductive potential who are not willing to employ highly effective birth control from screening to 4 months after the last dose of osimertinib\n- Patients who are unable to consent [§ 40 Abs. 1 S. 3 Nr. 3a AMG]\n- Previous enrolment in the present study\n- 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\n- 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\n- Cardiac side-effects of osimertinib not sufficiently improved by dose reduction as suggested by the label/ Fachinformation\n- 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\n- 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.\n- Congenital long QT syndrome"}

Primary endpoints

• {"endpoint_text":"- 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.","definition_or_measurement_approach":"Adverse Events graded according to CTCAE V5.0; includes frequency, time of onset and severity; specific AEs of special interest enumerated."}
• {"endpoint_text":"- Pneumonitis. A consensus definition of pneumonitis based on symptoms, clinical examination, imaging and pulmonary function testing, as well as any available bronchoscopy results, will be used. In the absence of bronchoscopy, pharyngeal wash should be used to exclude viral infections. Care should be taken to differentiate between drug-induced and radiation-induced pneumonitis, by taking into account the localization and time of onset relative to treatment","definition_or_measurement_approach":"Consensus definition using symptoms, clinical exam, imaging, pulmonary function testing, bronchoscopy if available; pharyngeal wash if no bronchoscopy; differentiate drug- vs radiation-induced by localization and timing."}
• {"endpoint_text":"- Radionecrosis: A consensus definition of radionecrosis based on imaging and clinical consultation will be used","definition_or_measurement_approach":"Consensus definition based on imaging and clinical consultation."}

Secondary endpoints

• {"endpoint_text":"- Progression-free survival (PFS), calculated as PFS1, PFS2, PFS3, PFS0 to assess osimertinib treatment continued beyond several progression events entailing radiotherapy, and prior to first radiotherapy","definition_or_measurement_approach":"PFS calculated in multiple definitions (PFS1, PFS2, PFS3, PFS0) to assess continued osimertinib through progression events and relative to radiotherapy timing."}
• {"endpoint_text":"- Time to treatment failure (TTF)","definition_or_measurement_approach":""}
• {"endpoint_text":"- Local tumor control","definition_or_measurement_approach":""}
• {"endpoint_text":"- Overall survival (OS)","definition_or_measurement_approach":""}
• {"endpoint_text":"- Quality of Life assessed by EORTC QLQ-C30","definition_or_measurement_approach":"QoL measured using EORTC QLQ-C30 instrument."}
• {"endpoint_text":"- Optional tumor tissue analysis (pre-study FFPE sample) and biomarker correlation with patient baseline characteristics and outcomes","definition_or_measurement_approach":"Optional analysis of pre-study FFPE tumor tissue and correlation of biomarkers with baseline characteristics and outcomes."}
• {"endpoint_text":"- Target volume of irradiation","definition_or_measurement_approach":""}
• {"endpoint_text":"- Type of irradiation (conventional, stereotactic)","definition_or_measurement_approach":""}

Germany

Earliest CTIS Part Ii Submission Date

04-06-2024

Latest Decision Or Authorization Date

07-05-2025

Processing Time Days

337

Number Of Sites

10

Number Of Participants

40

Primary sponsor

Full Name

AIO-Studien-gGmbH

Organisation Type

Laboratory/Research/Testing facility

Country Of Registered Address

Germany

Third parties

• {"country":"","full_name":"AstraZeneca GmbH","duties_or_roles":"Source of monetary support","organisation_type":""}