Durvalumab Plus Chemotherapy in Untreated Patients With Extensive-Stage Small Cell Lung Cancer

Study Overview
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Brief Summary
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This is a Phase IIIb, interventional, single arm, multicentre study to evaluate safety, effectivenees, use of resources and patient reporting outcomes in patients with ES-SCLC treated with durvalumab in combination with platinum-etoposide as first-line treatment in Spain.

Detailed Description
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This trial will provide an opportunity to further evaluate the safety profile and efficacy of durvalumab + EP in patient population that is reflective of real-world clinical practice, Durvalumab will be concurrently administered with first-line chemotherapy (EP) on an every 3 week (q3w) schedule for 4 to 6 cycles, and will continue to be administered as monotherapy post-chemotherapy on an every 4 week (q4w) schedule until confirmed progressive disease (PD) or unacceptable toxicity. Prophylactic cranial irradiation (PCI) is allowed in patients showing complete or partial responses after the durvalumab + EP combination cycles, at the discretion of the investigator according to their local clinical practice.

Official Title
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A Phase IIIB, Single Arm Study, of Durvalumab in Combination With Platinum-Etoposide for Untreated Patients With Extensive-Stage Small Cell Lung Cancer Reflecting Real World Clinical Practice in Spain (CANTABRICO).

Conditions
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Small Cell Lung Carcinoma Extensive Disease

Intervention / Treatment
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* Drug: Durvalumab
* Drug: Cisplatin
* Drug: Etoposide
* Drug: Carboplatin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically or cytologically documented Small cell Lung Cancer with extensive disease. Patients who had received chemoradiotherapy for LS-SCLC and have experienced a treatment-free interval of at least 6 months since last chemotherapy, radiotherapy, or chemoradiotherapy cycle, can be included under investigator criteria. Brain metastases; must be asymptomatic or have been treated at least 2 weeks prior to study treatment and are currently receiving 10 mg/day or less of prednisone or equivalent. Patients must be considered suitable to receive a platinum-based chemotherapy regimen as 1st line treatment for ES-SCLC. ECOG Performance Status of 0-2 at enrolment. No prior exposure to immune-mediated therapy for cancer. Adequate hematologic and organ function. Life expectancy of at least 12 weeks. Body weight >30 kg. Exclusion Criteria: Any history of radiotherapy to the chest prior to systemic therapy or planned consolidation chest radiation therapy (except paliative care outside of the chest). Paraneoplastic syndrome of autoimmune nature, requiring systemic treatment or clinical symptomatology suggesting worsening of PNS Active infection including tuberculosis, HIV, hepatitis B anc C Active or prior documented autoimmune or inflammatory disorders Uncontrolled intercurrent illness, including but not limited to interstitial lung disease.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Durvalumab in Combination with Platinum-Etoposide<br>Durvalumab 1500 mg via IV infusion will be concurrently administered with first-line chemotherapy (EP) on an every 3 week (q3w) schedule for 4 to 6 cycles, and will continue to be administered post-chemotherapy on an every 4 week (q4w) schedule until confirmed progressive disease (PD) or unacceptable toxicity. | Drug: Durvalumab<br>* Durvalumab 1500 mg via IV infusion over 60 minutes on Day 1 of each cycle.<br>Drug: Cisplatin<br>* Cisplatin as an IV infusion per local standards (usually over 60 to 120 minutes on Day 1) of each cycle.<br>Drug: Etoposide<br>* Etoposide sequentially administered per local standards (usually over 30 to 60 minutes IV infusion) on Days 1, 2, and 3 of each cycle.<br>Drug: Carboplatin<br>* Carboplatin as an IV infusion per local standards (usually over 30 to 60 minutes on Day 1) of each cycle.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of grade ≥ 3 Adverse Events (AE) |  | Up to 18 months | 
| Incidence of Immune Mediated Adverse Events (imAE). |  | Up to 18 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival (PFS). | PFS, defined as the time from initiation of study treatment to the first occurrence of disease progression or death from any cause, whichever occurs first. PFS will be calculated based on disease status evaluated by the investigator according to Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1) | Up to 18 months | 
| PFS rate at 6 months (PFS6). | PFS at 6 months, defined as the proportion of participants remaining alive without disease progression at 6 months after initiation of study treatment. | Up to 6 months | 
| PFS rate at 1 year (PFS12). | PFS at 1 year, defined as the proportion of participants remaining alive without disease progression at 1 year after initiation of study treatment. | Up to 12 months | 
| Objective Response Rate (ORR): using site investigator assessments according to RECIST 1.1. | ORR, defined as the percentage of patients who attain complete response (CR) or partial response (PR) according to RECIST v1. | Up to 18 months | 
| Duration of Response (DoR). | Duration of response (DOR), defined as the time from initial response to disease progression or death among patients who have experienced a CR or PR (unconfirmed) during the study. Duration of response will be calculated based on disease status evaluated by the investigator according to RECIST v1.1. | Up to 18 months | 
| DoR rate at 1 year (DoR12) | DoR at 1 year, defined as the proportion of participants having CR or PR (unconfirmed) at 1 year after initiation of study treatment. | Up to 12 months | 
| Time to Treatment Discontinuation (TTD). | Defined as the time in months between first and last study treatment dose. | Up to 18 months | 
| Overal Survival (OS). | OS, defined as the time from initiation of study treatment to death from any cause. | Up to 18 months | 
| OS rate at 6 months. | OS at 6 months, defined as the proportion of participants remaining alive at 6 months after initiation of study treatment. | Up to 6 months | 
| OS rate at 1 year. | OS at 1 year, defined as the proportion of participants remaining alive at 1 year after initiation of study treatment. | Up to 12 months | 
| OS rate at 18 months. | OS at 18 months, defined as the proportion of participants remaining alive at 18 months after initiation of study treatment. | Up to 18 months | 
| Change from baseline in symptoms and quality of life as assessed by European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 items (EORTC QLQ-C30) and Questionnaire-Lung Cancer 13 (EORTC QLQ-LC13). |  | Up to 18 months | 
| Changes from baseline in PRO-CTCAE. |  | Up to 18 months | 
| Number of visits to oncology service, emergency visits, outpatient visits, imaging tests and biopsy-related procedures and number and length of hospitalizations. |  | Up to 18 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Extensive-Stage, ICI, SCLC, Durvalumab