Standard of care for Extensive-Stage Disease (ED) Small Cell Lung Cancer (SCLC) as first-line treatment is 4 to 6 cycles of platinum based chemotherapy (carboplatin or cisplatin) in combination with etoposide. However, the outcome of the disease remains poor with a median overall survival of approximately 10 months, mainly caused by rapid development of drug resistance. The risk of intrathoracic recurrences can be reduced and an improved 2-year survival can be achieved with the addition of thoracic radiotherapy (tRT). The main objective of the trial is to evaluate the efficacy of tRT combined with maintenance durvalumab in SCLC after chemoimmunotherapy. Secondary objective is to evaluate the safety of tRT combined with maintenance durvalumab in SCLC after chemo-immunotherapy. For this trial durvalumab is the IMP. Patients will start with an induction phase (part 1): Patients will receive durvalumab in combination with carboplatin and etoposide for 4 cycles of 21 days. Patients with CR; PR or SD after the induction phase, will transfer to the maintenance phase (part 2): Patients will receive durvalumab treatment up to PD or max. 2 years, i.e. 26 maintenance cycles, in combination with tRT. Patients with PD after the induction phase will transfer to the follow-up phase: Patients will be followed up for 24 months, every 8 weeks.
The prognosis of patients with advanced small cell lung cancer is poor. Despite chemotherapy and immunotherapy, median survival is only 12 months. The trial SAKK 15/19 is investigating whether thoracic radiotherapy and the administration of durvalumab can slow down the progression of the disease. In patients with advanced small cell lung cancer, the standard therapy consists of 4-6 cycles of platinum-based chemotherapy plus etoposide with or without Atezolizumab. Nevertheless, the median overall survival of these patients is only 10-12 months, because resistance to the therapy usually develops rapidly. Radiotherapy and maintenance therapy with Durvalumab to activate the immune system The risk of intrathoracic progression of small cell lung cancer can be reduced by additional thoracic radiotherapy. It is assumed that the radiation not only has a direct cytotoxic effect on the tumor cells, but also stimulates an antitumor immune response. In the trial SAKK 15/19, it is being investigated whether the combination of the monoclonal anti-PD-L1 antibody durvalumab with thoracic radiotherapy in patients with advanced small cell lung cancer can cause an even stronger activation of the immune system with an improved antitumoral immune response. The trial therapy (thoracic radiotherapy + durvalumab) is based on chemo-immunotherapy with carboplatin, etoposide and durvalumab. The primary endpoint of the trial is the progression-free rate after 12 months, secondary endpoints include progression-free survival, median overall survival and objective response rate. Which patients can participate? The trial is open to patients with advanced small-cell lung cancer who have either metastases (stage IV) or whose lung tumor volume is so large that radiation therapy with curative intent is not possible as a first-line therapy (stage III-IV). Patients who have already received systemic therapy or thoracic radiotherapy because of the small cell lung carcinoma cannot participate. Conduct of the trial Participation in the trial is carried out in three phases for patients: * Induction therapy: Patients receive four cycles of chemo-immunotherapy with carboplatin, etoposide and durvalumab. One cycle lasts 21 days. In those patients who show a response or stable disease situation after completion of induction therapy, maintenance therapy follows. Maintenance therapy is not performed in patients whose disease has progressed further under induction therapy. * Maintenance therapy: Thoracic radiotherapy for 2.5-3 weeks (13 fractions of 3 Gray each) and administration of Durvalumab every 28 days for a maximum of two years. * Follow-up for two years.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
46
Durvalumab: 1500 mg iv
Carboplatin: AUC 5 mg/mL/min iv
Etoposide: 100 mg/m2 iv
Thoracic radiotherapy: 39 Gy in 13 fractions, starting 3-8 weeks after day 1 of last cycle of induction treatment, over 2.5 weeks Prophylactic cranial irradiation (PCI) is allowed but optional: according to local practice, starting 3-8 weeks after day 1 of last cycle of induction treatment Follow up phase Patients will be followed up for 24 months, every 8 weeks.
Kantonsspital Aarau
Aarau, Switzerland
Universitaetsspital Basel
Basel, Switzerland
IOSI Ospedale Regionale di Bellinzona e Valli
Bellinzona, Switzerland
Inselspital Bern
Bern, Switzerland
Kantonsspital Graubuenden
Chur, Switzerland
Hôpitaux Universitaires de Genève
Geneva, Switzerland
Klinik Hirslanden
Männedorf, Switzerland
Spital Männedorf
Männedorf, Switzerland
Kantonsspital Olten
Olten, Switzerland
Kantonsspital - St. Gallen
Sankt Gallen, Switzerland
...and 4 more locations
Progression-free rate (PFR) (RECIST v.1.1)
PFR (RECIST v.1.1) at 12 months after registration, defined by the Kaplan-Meier estimator for progression-free survival (RECIST v.1.1) at 12 months (+ 4 weeks as we allow 4 weeks delay in the tumor assessment at 12 months).
Time frame: at 12 months after registration
Progression-free survival (PFS) (RECIST v.1.1)
PFS (RECIST v.1.1), defined as the time from registration until progression according to RECIST v1.1 or death from any cause, whichever occurs first. Patients without an event at the time of analysis and patients starting a new anticancer therapy in the absence of an event will be censored at the date of the last tumor assessment before the start of the new therapy, if any.
Time frame: From the date of registration until the date of progressive disease according to RECIST v1.1 or death, whichever occurs first, assessed up to 4 years after registration.
Progression-free survival (PFS) (RECIST v.1.1) outside the brain
PFS (RECIST v.1.1) outside the brain, defined as progression-free survival, except that relapses in the brain will be censored.
Time frame: From the date of registration until the date of progressive disease according to RECIST v1.1 or death, whichever occurs first, assessed up to 4 years after registration
Progression-free survival (RECIST v.1.1) after induction chemotherapy (PFS-IND)
PFS-IND defined as the time from completion of induction chemotherapy until progression according to RECIST v1.1 or death from any cause, whichever occurs first. Patients without an event at the time of analysis and patients starting a new anticancer therapy in the absence of an event will be censored at the date of the last tumor assessment before the start of the new therapy, if any. PFS-IND will only be analyzed in patients who had CR, PR or SD after induction chemotherapy and started radiotherapy maintenance.
Time frame: From the date of completion of induction chemotherapy until the date of progressive disease according to RECIST v1.1 or death, whichever occurs first, assessed up to 4 years after registration
Overall Survival (OS)
OS defined as the time from registration until death from any cause. Patients without an event at the time of analysis will be censored at the date they were last known to be alive.
Time frame: From the date of registration until the date of death, assessed up to 4 years after registration
Objective response rate (ORR)
ORR defined as proportion of patients achieving complete response (CR) or partial response (PR) according to RECIST v1.1 during trial treatment.
Time frame: From the date of registration until the date of progressive disease according to RECIST v1.1 or death, whichever occurs first, assessed up to 4 years after registration
Duration of response (DOR)
DOR defined as time from the date when a patient first meets the criteria for CR or PR according to RECIST v1.1, until documented progression, relapse or death due to disease progression, whichever occurs first. Patients without an event at the time of analysis and patients starting a new anticancer therapy in the absence of an event will be censored at the date of the last tumor assessment before the start of the new therapy, if any. DOR will only be analyzed in patients achieving CR or PR during trial treatment.
Time frame: From the date of first CR or PR according to RECIST v1.1 until the date of progressive disease according to RECIST v1.1, relapse or death, whichever occurs first, assessed up to 4 years after registration
Adverse events (AEs)
AEs assessed according to NCI CTCAE 5.0.
Time frame: From the date of registration to 90 days after last trial treatment
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