Tests radiation for leftover lung tumors during osimertinib treatment

Trial details

Who runs it

Centro de Tratamiento e Investigación sobre Cáncer, Luis Carlos Sarmiento Angulo

Trial code

NCT05998993

Record updated

21 August 2023

Original description

Phase II Study to Evaluate the Impact of SBRT (Stereotactic Body Radiation Therapy) and/or SRS (Stereotactic Radiosurgery) on Oligoresidual Disease in EGFR Mutation Patients Treated with Osimertinib as First-Line Systemic Intervention. All candidates must exhibit a partial response after 12 weeks of treatment with the third-generation tyrosine kinase inhibitor (alone or in combination with chemotherapy) and a maximum of five (5) residual lesions in a maximum of two (2) organs. The primary outcome will be progression-free survival (PFS), and secondary outcomes will include overall survival (OS), proportion of patients without progression at months 12 and 36, safety, and overall response rate (ORR). Additionally, an exploratory analysis will be conducted on the prognostic value of liquid biopsy (supplementary information), considering baseline presence of mutations (determined by Next Generation Sequencing tests) and reduction or negativization of allelic fraction (AF).Read full original descriptionShow less

Phase II Study to Evaluate the Efficacy and Safety of SBRT as an Adjunctive Intervention for Oligoresidual Disease in EGFR Mutant NSCLC With First-Line Osimertinib Treatment

Phase II Study to Evaluate the Impact of SBRT (Stereotactic Body Radiation Therapy) and/or SRS (Stereotactic Radiosurgery) on Oligoresidual Disease in EGFR Mutation Patients Treated with Osimertinib as First-Line Systemic Intervention. All candidates must exhibit a partial response after 12 weeks of treatment with the third-generation tyrosine kinase inhibitor (alone or in combination with chemotherapy) and a maximum of five (5) residual lesions in a maximum of two (2) organs. The primary outcome will be progression-free survival (PFS), and secondary outcomes will include overall survival (OS), proportion of patients without progression at months 12 and 36, safety, and overall response rate (ORR). Additionally, an exploratory analysis will be conducted on the prognostic value of liquid biopsy (supplementary information), considering baseline presence of mutations (determined by Next Generation Sequencing tests) and reduction or negativization of allelic fraction (AF).

Inclusion: Be older than 18 years of age; Be capable of giving informed consent to participate in the study; Have histological confirmation compatible with EGFR mutant non-small cell lung cancer (NSCLC) and metastatic disease (with or without histological confirmation of metastatic lesions); Have confirmation of the presence of common EGFR mutations (exon 19 deletion, L858R/exon 21, or G719X) through any locally and internationally accepted standard tests; Have received at least 12 weeks of Osimertinib treatment (with or without the addition of chemotherapy based on FLAURA2 study results after discussion with the investigative team); Have a partial response defined by RECIST 1.1 criteria; Have a maximum of 5 residual tumor lesions in up to 2 organs suitable for treatment with Stereotactic Ablative Radiotherapy (SABR); Have the following imaging and clinical tests within 4 weeks before study entry:; Contrast-enhanced brain MRI; Chest/abdomen/pelvis CT scan, with or without bone scan (at the investigator's discretion) if PET-CT was not performed; 18-FDG PET-CT; Spinal MRI for patients with vertebral or paravertebral metastases; Electrocardiogram (EKG) and transthoracic echocardiogram; Complete blood count and standard blood chemistry; Negative pregnancy test for fertile women within 4 weeks prior to starting radiotherapy; Liquid biopsy for assessment of tumor allelic fraction (baseline); ECOG performance status 0-2; All sites of oligoresidual disease must be safely treatable according to the following criteria:; All brain lesions must be treatable with SRS; The maximum size for extracranial lesions will be up to 6 cm, with exceptions for bone metastases which may include lesions larger than 6 cm at the discretion of the investigative medical team (e.g., ribs, scapula, or pelvis); Life expectancy >6 months; Not eligible for surgical treatment; Osimertinib treatment must be suspended 48 hours before the start of ablative therapy and cannot be initiated within 48 hours of receiving the last fraction. In patients receiving SBRT for central lung lesions, the suspension time for Osimertinib may be extended up to 5 days before and after ablative therapy; Patients may have previously received treatments such as radiofrequency or microwave ablation for oligoresidual lesions, but imaging must demonstrate that the lesion persists and is treatable with SABR; Metastatic tumor lesions that received initial treatment with radiosurgery cannot be included for SABR treatment; If initial treatment was conventional radiotherapy, SABR could be considered if safe to administer. In this case, the ablative therapy must be discussed by the investigative team; The eligibility and prognosis criteria will be reviewed by the multidisciplinary thoracic tumor board at CTIC Centro de Tratamiento e Investigación Sobre Cáncer Luis Carlos Sarmiento Angulo.

Exclusion: Severe comorbidities contraindicating radiation therapy; Candidate for a clinical trial with an experimental drug; Complete response to Osimertinib treatment (no oligoresidual disease for ablative treatment); History of pneumonitis or functionally limiting interstitial lung disease. It may be considered limiting if the patient is unable to perform DLCO maneuvers or if adjusted DLCO is less than 35% of predicted, PaO2 at Bogotá altitude with FiO2 21% is less than or equal to 50 mmHg; Dominant brain metastatic disease requiring surgical management (e.g., imminent herniation or hydrocephalus); Oligoresidual involvement in peritoneum, pleura, or bone marrow (non-measurable disease); Bone metastases in the femur with a high risk of fracture; Inability to treat all oligoresidual lesions with ablative intent; Clinical or radiological evidence of symptomatic spinal cord compression; Inability to receive Osimertinib with minimal adherence; Leptomeningeal involvement (presumed based on imaging findings or confirmed by cerebrospinal fluid cytology); Pregnant or breastfeeding women.

ClinicalTrials.gov NCT05998993