Evaluation of Durvalumab in Combination with Cisplatin, Carboplatin, and Etoposide with Radiotherapy in Extensive-Stage Small Cell Lung Cancer

The primary objective of this study is to evaluate the **feasibility** of a treatment regimen for patients with extensive stage small cell lung cancer (SCLC). This regimen involves the administration of thoracic radiotherapy in conjunction with a combination of platinum-based chemotherapy (cisplatin or carboplatin), etoposide, and **durvalumab**. Following this, the study aims to assess the feasibility of stereotactic radiotherapy administered alongside durvalumab maintenance therapy. The clinical relevance of this objective lies in determining whether this combined treatment approach can be effectively implemented in a clinical setting, potentially offering a new therapeutic strategy for patients with extensive stage SCLC.

Additionally, the study seeks to investigate the efficacy of this treatment scheme in improving the progression-free survival (PFS) rate at 12 months. This secondary objective is crucial for understanding the potential long-term benefits of the treatment regimen in delaying disease progression in this patient population.

The clinical trial involves participants diagnosed with **extensive stage small cell lung cancer (SCLC)**. The study population includes both male and female subjects, with an age range corresponding to categories 3 and 4, which typically represent adults and older adults. Participants are required to have a stable disease or partial response according to RECIST 1.1 criteria after prior treatment with platinum/etoposide/durvalumab. The trial does not include vulnerable populations. Participants must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, indicating they are fully active or restricted in physically strenuous activity but ambulatory. The sponsor has not provided the total number of participants. Lifestyle factors such as diet and physical activity are not specified. Key inclusion criteria include a histologically confirmed first diagnosis of ES-SCLC and a life expectancy of at least 12 weeks. The trial population was selected based on these criteria, ensuring a focus on individuals with specific disease characteristics and treatment responses.

The clinical trial is designed to evaluate the feasibility and efficacy of a treatment regimen for **extensive stage small cell lung cancer (SCLC)**. This trial is a Phase II, randomized, double-blind, controlled study. The primary objective is to assess the one-year progression-free survival (PFS) rate using investigator assessments according to RECIST 1.1 criteria. The trial is expected to commence recruitment on October 30, 2024, and conclude by September 30, 2026. Participants will be involved in the study for a maximum treatment period of 48 weeks, with the possibility of early termination if specific conditions arise, such as adverse reactions or disease progression.

The study involves several key visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as a histologically confirmed first diagnosis of ES-SCLC and an ECOG performance status of 0 or 1. Following the screening, participants will undergo treatment cycles involving **cisplatin**, **carboplatin**, **durvalumab**, and **etoposide**, administered via intravenous infusion. The treatment scheme includes thoracic radiotherapy concomitant with platinum/etoposide/durvalumab therapy, followed by stereotactic radiotherapy with durvalumab maintenance. Follow-up visits will be scheduled to monitor the participants' response to treatment and any potential side effects. The end-of-study visit will assess the overall outcomes and gather final data on the efficacy and safety of the treatment regimen.

Participants are expected to adhere to the study protocol throughout the trial duration. Conditions that may lead to early termination include non-compliance with the study protocol, withdrawal of consent, or any medical condition that contraindicates continued participation. The trial aims to provide valuable insights into the treatment of extensive stage SCLC, with the potential to improve patient outcomes through a novel combination of therapies.

The clinical trial involves the administration of several experimental medications, each with specific pharmaceutical forms, dosages, and routes of administration. **Cisplatin**, marketed as Cisplatin NeoCorp 1 mg/ml, is provided as a **solution for infusion**. It is administered via **intravenous infusion** with a maximum daily dose of 75 mg/m² and a total dose not exceeding 150 mg/m² over a treatment period of up to 4 weeks. The active substance, cisplatin, is of chemical origin and is produced by HEXAL AG.

**Carboplatin**, under the brand name Carbomedac 10 mg/ml, is also a **solution for infusion**. It is administered through **intravascular use** with a maximum daily dose of 5 mg and a total dose of 10 mg over a 4-week treatment period. The active substance, carboplatin, is chemically derived and manufactured by MEDAC GESELLSCHAFT FÜR KLINISCHE SPEZIALPRÄPARATE MBH (WEDEL).

**Durvalumab**, known commercially as IMFINZI 50 mg/mL, is a **concentrate for solution for infusion**. It is administered via **intravenous use** with a maximum daily dose of 1500 mg and a total dose of 19500 mg over a treatment period of up to 48 weeks. The active substance, durvalumab, is a protein of other origin, produced by ASTRAZENECA AB.

**Etoposide**, marketed as Eto-GRY® 20 mg/ml, is provided as a **solution for injection**. It is administered through **intravenous infusion** with a maximum daily dose of 90 mg/m² and a total dose of 540 mg/m² over a 4-week treatment period. The active substance, etoposide, is of chemical origin and is produced by TEVA GMBH.

In this clinical trial, no non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments are specified. Participant compliance with the dosing schedules is monitored throughout the study to ensure adherence to the treatment protocols. The trial aims to evaluate the feasibility and efficacy of the treatment scheme in improving progression-free survival (PFS) rates at 12 months in patients with extensive-stage small cell lung cancer (SCLC).

The efficacy of the clinical trial will be assessed primarily through the evaluation of the one-year **progression-free survival (PFS)** rate. This will be determined using investigator assessments in accordance with the RECIST 1.1 criteria. The trial aims to study the efficacy of a treatment scheme involving thoracic radiotherapy in combination with platinum/etoposide/durvalumab therapy, followed by stereotactic radiotherapy with durvalumab maintenance, specifically targeting extensive stage small cell lung cancer (ES-SCLC).