PACCELIO - FDG-PET Based Small Volume Accelerated Immuno Chemoradiotherapy in Locally Advanced NSCLC
Multinational, randomized, controlled, open-label, multicenter phase II trial. Eligible patients will be randomized in a ratio of 1:1 to Experimental Arm (FDG-PET-based small volume accelerated radiotherapy with concurrent standard of care chemotherapy) or Conventional Arm (standard FDG-PET-based radiotherapy with concurrent standard of care chemotherapy). Patients showing complete response, partial response, or stable disease following chemoradiotherapy will receive standard of care consolidation therapy with durvalumab (fixed dose of 1500 mg q4w) for up to 12 months or until progression of disease, unacceptable toxicity, patient´s wish, or investigator´s decision, whichever comes first. After end of durvalumab therapy, patients will undergo safety follow up for 90 (+7) days followed by survival follow up until overall end of study. Overall end of study will be reached 24 months after the last patient has started durvalumab therapy. Patients showing PD following chemoradiotherapy will be treated according to investigator´s decision but will be followed up until overall end of study.
• Written informed consent
• Patients irrespective of sex and gender, aged 18 years or older at the time of signing the ICF
• Patients must be willing and able to comply with scheduled visits, treatment schedule, laboratory testing, and other requirements of the study as determined by the investigator
• Patients with histologically or cytologically documented NSCLC who present with locally advanced, unresectable (Stage III) disease (according to version 8 of the International Association for the Study of Lung Cancer Staging Manual in Thoracic Oncology (IASLC Staging Manual in Thoracic Oncology 2016))
• Patients fit for simultaneous chemoradiotherapy and consolidation immunotherapy according to interdisciplinary consensus
• Histologically proven PD-L1-expression of ≥ 1% (tumor proportion score; TPS) in tumor sample as assessed in routine staging using a validated test such as Ventana SP236 assay
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1 at enrolment
• Tumor assessment by FDG-PET CT within 21 days prior to start of chemoradiotherapy.
• Adequate pulmonary function test results
‣ Pre- or post-bronchodilator forced expiratory volume 1 of 1.0 L or \>40% of predicted AND
⁃ Diffusing capacity of the lung for carbon monoxide (DLCO) \>30% of predicted
• Adequate bone marrow and organ function at enrolment
‣ Hemoglobin ≥9.0 g/dL
⁃ Absolute neutrophil count \>1.5 × 109/L
⁃ Platelet count \>100 × 109/L
⁃ Serum bilirubin ≤1.5 × upper limit of normal (ULN)
⁃ Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5 × ULN
⁃ Measured creatinine clearance (CrCl) \>40 mL/min or calculated CL \>40 mL/min as determined by Cockcroft-Gault (using actual body weight)
• Body weight of \>30 kg at enrolment
• Evidence of post-menopausal status, or negative urinary or serum pregnancy test for female pre-menopausal patients. Women will be considered post-menopausal if they are amenorrhoic for 12 months or more without an alternative medical cause. The following age-specific requirements apply:
‣ Women \<50 years old would be considered post-menopausal if they have been amenorrhoic for 12 months or more following cessation of exogenous hormonal treatments with luteinizing hormone and follicle-stimulating hormone levels in the post-menopausal range for the institution
⁃ Women ≥50 years old would be considered post-menopausal if they have been amenorrhoic for 12 months or more following cessation of all exogenous hormonal treatments, radiation-induced oophorectomy with last menses \>1 year ago, chemotherapyinduced menopause with \>1 year interval since last menses, or surgical sterilization (bilateral oophorectomy or hysterectomy)
• Women of childbearing potential (WOCBP) and male patients with partners of childbearing potential must agree to always use a highly effective form of contraception according to the Clinical Trials Facilitation and Coordination Group during the treatment phase of this study and for at least 90 days after the last dose durvalumab or 6 months after the last dose of chemotherapy, whichever occurs last