Studies have shown that combining chemotherapy and immune checkpoint inhibitors (ICI) prolongs survival compared with chemotherapy alone in extensive stage small-cell lung cancer (ES SCLC), but the survival benefit is modest. The main aim of this trial is to investigate whether there is a synergistic/additive effect of concurrent thoracic radiotherapy in ES SCLC patients receiving carboplatin/etoposide/durvalumab.
Studies show that adding ICI therapy to standard chemotherapy prolongs survival in ES SCLC. The survival benefit, however, is modest, and there is a need for more effective therapy. It has been hypothesized that there is a synergistic effect of combining ICI with radiotherapy. In this randomized phase III study, the main aim is to investigate whether concurrent thoracic radiotherapy of 30 Gy/10 fractions improves survival in ES SCLC patients receiving carboplatin/etoposide/durvalumab. It is currently not possible to classify the patients who benefit from ICIs in SCLC. In this study, biological material (tissue, blood, feces) which will be analyzed for potential predictive and prognostic biomarkers. Prophylactic cranial irradiation in ES SCLC is debated, mainly due to the potentially detrimental effect on cognition. Thus, frequency and timing of brain metastases and cognitive function will be assessed before, during and after study treatment.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
239
30Gy/10 fractions thoracic radiotherapy given between 2nd and 3rd course of chemo-immunotherapy.
Four courses of carboplatin/etoposide/durvalumab every 3 weeks followed by durvalumab every 4 weeks until intolerable toxicity, progressive disease leading to a need for other treatment, or until the patient no longer wishes to continue treatment.
North Estonia Medical Centre
Tallinn, Estonia
Landspitali University Hospital
Reykjavik, Iceland
Change in 1-year overall survival
The Cox proportional hazards method will be used to compare survival between the treatment groups.
Time frame: 14 months after last patient entry
Change in 2-, 3-, 4- and 5-year survival rate
The Cox proportional hazards method will be used to compare survival between the treatment groups.
Time frame: 2, 3, 4 and 5 years after last patient entry
Frequency and severity of adverse events
Adverse events will be compared between the treatment arms using the Pearson's Chi-square and Fisher's exact test.
Time frame: Through study completion, an average of 1 year after last patient entry
Change in progression free survival (PFS)
PFS will be estimated using the Kaplan-Meier method and compared using the log-rank test. A Cox-model adjusting for baseline characteristics will be used for multivariable analyses.
Time frame: Through study completion, an average of 1 year after last patient entry
Change in overall response rates
Response rates are compared using Pearson's Chi-square test.
Time frame: Through study completion, an average of 1 year after last patient entry
Change in response rates in non-irradiated lesions
Response rates are compared using Pearson's Chi-square test.
Time frame: Through study completion, an average of 1 year after last patient entry
Local control rates in the thorax
Local control rates are compared using Pearson's Chi-square test.
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Erasmus MC
Rotterdam, Netherlands
Ålesund Hospital
Ålesund, Norway
Haukeland Universitetssykehus
Bergen, Norway
Nordlandssykehuset HF
Bodø, Norway
Drammen sykehus - Vestre Viken
Drammen, Norway
Innlandet hospital Gjøvik
Gjøvik, Norway
Haugesund hospital
Haugesund, Norway
Sykehuset Levanger
Levanger, Norway
...and 10 more locations
Time frame: Through study completion, an average of 1 year after last patient entry
Health-related quality of life (HRQoL)
All HRQoL scores will be transformed to a scale of 0-100 according to the EORTC QLQ scoring manual. Mean scores will be compared at each assessment timepoint, and a difference of 10 points is considered clinically relevant.
Time frame: Through study completion, an average of 1 year after last patient entry