Chemo-immunotherapy Plus Thoracic Radiotherapy in Extensive Stage Small-cell Lung Cancer

Phase 3

Recruiting

• Conditions: Small-cell Lung Cancer
• Interventions: Drug: Chemo-immunotherapy; Procedure: Thoracic radiotherapy

• Registration Number: NCT05223647
• Lead Sponsor: Norwegian University of Science and Technology

Brief Summary

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.

Detailed Description

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 Timeline

• Study Start: 2022-01-11
• Study First Submitted: 2022-01-11
• Study First Submitted QC: 2022-02-03
• Study First Posted: 2022-02-04
• Status Verified: 2024-01
• Last Update Submitted: 2024-01-02
• Last Update Posted: 2024-01-05
• Primary Completion: 2026-01
• Study Completion: 2029-10

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 302

Inclusion Criteria

1. Age > 18 years at time of study entry
2. ECOG performance status of 0 or 1
3. Body weight >30 kg
4. Adequate bone marrow, liver and kidney function
5. Life expectancy of at least 3 months
6. At least one measurable (RECIST 1.1), thoracic lesion that can be irradiated with 30 Gy/10 fractions
7. Histologically or cytologically confirmed SCLC
8. Stage III-IV disease (TNM v8)
9. FEV1 >1 L or >30 % of predicted value and DLCO >30 % of predicted value
10. Patients with brain metastases are eligible provided they are asymptomatic or treated and stable on steroids and/or anticonvulsants prior to the start of treatment

Exclusion Criteria

1. Previous chemo-, immuno- or radiotherapy for SCLC
2. Major surgical procedure last 28 days
3. History of allogenic organ transplantation, autoimmune disease, immunodeficiency, hepatitis or HIV
4. Uncontrolled intercurrent illness
5. Other active malignancy
6. Leptomeningeal carcinomatosis
7. Immunosuppressive medication
8. Pregnant or breastfeeding women

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Chemo-immunotherapy	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.
Chemo-immunotherapy plus thoracic radiotherapy	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. Thoracic radiotherapy of 30 Gy/10 fractions between 2nd and 3rd carboplatin/etoposide/durvalumab course.
Chemo-immunotherapy plus thoracic radiotherapy	Thoracic radiotherapy	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. Thoracic radiotherapy of 30 Gy/10 fractions between 2nd and 3rd carboplatin/etoposide/durvalumab course.

Primary Outcome Measures

Name	Time	Method
Change in 1-year overall survival	14 months after last patient entry	The Cox proportional hazards method will be used to compare survival between the treatment groups.

Secondary Outcome Measures

Name	Time	Method
Change in overall response rates	Through study completion, an average of 1 year after last patient entry	Response rates are compared using Pearson's Chi-square test.
Local control rates in the thorax	Through study completion, an average of 1 year after last patient entry	Local control rates are compared using Pearson's Chi-square test.
Change in progression free survival (PFS)	Through study completion, an average of 1 year after last patient entry	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.
Change in 2-, 3-, 4- and 5-year survival rate	2, 3, 4 and 5 years after last patient entry	The Cox proportional hazards method will be used to compare survival between the treatment groups.
Frequency and severity of adverse events	Through study completion, an average of 1 year after last patient entry	Adverse events will be compared between the treatment arms using the Pearson's Chi-square and Fisher's exact test.
Change in response rates in non-irradiated lesions	Through study completion, an average of 1 year after last patient entry	Response rates are compared using Pearson's Chi-square test.
Health-related quality of life (HRQoL)	Through study completion, an average of 1 year after last patient entry	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.

Trial Locations

Locations (20)

Drammen sykehus - Vestre Viken; 🇳🇴 Drammen, Norway

Akershus Universitetssykehus AHUS; 🇳🇴 Oslo, Norway

Karolinska University Hospital; 🇸🇪 Stockholm, Sweden

Linköping University Hospital; 🇸🇪 Linköping, Sweden

Lund University Hospital; 🇸🇪 Skåne, Sweden

North Estonia Medical Centre; 🇪🇪 Tallinn, Estonia

Haukeland Universitetssykehus; 🇳🇴 Bergen, Norway

Sykehuset Levanger; 🇳🇴 Levanger, Norway

Stavanger University Hospital; 🇳🇴 Stavanger, Norway

Gävle hospital; 🇸🇪 Gävle, Sweden

Sahlgrenska Sjukehuset; 🇸🇪 Göteborg, Sweden

Landspitali University Hospital; 🇮🇸 Reykjavík, Iceland

Erasmus MC; 🇳🇱 Rotterdam, Netherlands

Innlandet hospital Gjøvik; 🇳🇴 Gjøvik, Norway

Cancer Clinic at St. Olavs Hospital; 🇳🇴 Trondheim, Norway

Nordlandssykehuset HF; 🇳🇴 Bodø, Norway

Haugesund hospital; 🇳🇴 Haugesund, Norway

Oslo University Hospital Ullevål; 🇳🇴 Oslo, Norway

University Hospital of North Norway, Pulmonology Department; 🇳🇴 Tromsø, Norway

Ålesund Hospital; 🇳🇴 Ålesund, Norway