Thoracic Radiotherapy Plus Maintenance Durvalumab After First Line Carboplatin and Etoposide Plus Durvalumab in Extensive-stage Disease Small Cell Lung Cancer (ED-SCLC).

Lung Cancer Clinical Trial

Official title: Thoracic Radiotherapy Plus Maintenance Durvalumab After First Line Carboplatin and Etoposide Plus Durvalumab in Extensive-stage Disease Small Cell Lung Cancer (ED-SCLC). A Multicenter Single Arm Open Label Phase II Trial.

Status Active, not recruiting

Clinical Trial Summary

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.

Clinical Trial Description

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. ;

Related Conditions & MeSH terms

• Lung Cancer
• Lung Neoplasms
• Small Cell Lung Cancer
• Small Cell Lung Carcinoma

• NCT number: NCT04472949
• Study type: Interventional
• Source: Swiss Group for Clinical Cancer Research
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: June 25, 2021
• Completion date: December 2027