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

Randomized Phase III Trial Investigating the Survival Benefit of Adding Thoracic Radiotherapy to Durvalumab (MEDI4736) Immunotherapy Plus Chemotherapy in Extensive Stage Small-cell Lung Cancer

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.

Study Overview

• Status: Terminated
• Conditions: Small-cell Lung Cancer
• Intervention / Treatment: Procedure: Thoracic radiotherapy; Drug: Chemo-immunotherapy

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 Type: Interventional
• Enrollment (Actual): 239
• Phase: Phase 3

Contacts and Locations

Study Locations

• Estonia
  • Tallinn, Estonia
    • North Estonia Medical Centre
• Iceland
  • Reykjavik, Iceland
    • Landspitali University Hospital
• Netherlands
  • Rotterdam, Netherlands
    • Erasmus MC
• Norway
  • Bergen, Norway
    • Haukeland Universitetssykehus
  • Bodø, Norway
    • Nordlandssykehuset HF
  • Drammen, Norway
    • Drammen sykehus - Vestre Viken
  • Gjøvik, Norway
    • Innlandet Hospital Gjøvik
  • Haugesund, Norway
    • Haugesund Hospital
  • Levanger, Norway
    • Sykehuset Levanger
  • Oslo, Norway
    • Oslo University Hospital Ullevål
  • Oslo, Norway
    • Akershus Universitetssykehus AHUS
  • Stavanger, Norway
    • Stavanger University Hospital
  • Tromsø, Norway
    • University Hospital of North Norway, Pulmonology Department
  • Trondheim, Norway
    • Cancer Clinic at St. Olavs Hospital
  • Ålesund, Norway
    • Ålesund Hospital
• Sweden
  • Gothenburg, Sweden
    • Sahlgrenska Sjukehuset
  • Gävle, Sweden
    • Gävle hospital
  • Linköping, Sweden
    • Linköping University Hospital
  • Skåne, Sweden
    • Lund University Hospital
  • Stockholm, Sweden
    • Karolinska University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Chemo-immunotherapy plus 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.	Procedure: Thoracic radiotherapy; 30Gy/10 fractions thoracic radiotherapy given between 2nd and 3rd course of chemo-immunotherapy.; Drug: 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.; Other Names: carboplatin/etoposide/durvalumab
Active Comparator: 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.	Drug: 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.; Other Names: carboplatin/etoposide/durvalumab

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in cognitive function from baseline to end of treatment	Cognitive function will be compared between patients who receive PCI and those who do not, using the MoCA-test. Scores will be compared using the Mann-Whitney test.	Through study completion, an average of 2 years after last patient entry
Frequency and timing of brain metastases	Changes in brain metastases are compared using Pearson's Chi-square test.	Through study completion, an average of 2 years after last patient entry
Associations between outcomes of study treatment and biomarkers in tissue, blood and stool	A detailed plan for analyses will be defined when sufficient material for translational research has been collected.	Through study completion, an average of 2 years after last patient entry

Collaborators and Investigators

• Sponsor: Norwegian University of Science and Technology
• Collaborators: Karolinska University Hospital; Oslo University Hospital; University Hospital of North Norway; Erasmus Medical Center; Helse Stavanger HF; Haukeland University Hospital; St. Olavs Hospital; Sykehuset Innlandet HF; Helse Nord-Trøndelag HF; Alesund Hospital; Helse Fonna; University Hospital, Akershus; University Hospital, Linkoeping; Nordlandssykehuset HF; Lund University Hospital; Landspitali University Hospital; Drammen sykehus; North Estonia Medical Centre; Gävle Hospital; Sahlgrenska University Hospital
• Investigators: Study Director: Magnus Steigedal, PhD, Department of Clinical and Molecular Medicine, NTNU

Study record dates

Study Major Dates

• Study Start (Actual): January 11, 2022
• Primary Completion (Actual): September 4, 2025
• Study Completion (Actual): September 4, 2025

Study Registration Dates

• First Submitted: January 11, 2022
• First Submitted That Met QC Criteria: February 3, 2022
• First Posted (Actual): February 4, 2022

Study Record Updates

• Last Update Posted (Actual): January 28, 2026
• Last Update Submitted That Met QC Criteria: January 26, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: chemotherapy; immunotherapy; cancer; radiotherapy
• Additional Relevant MeSH Terms: Neoplasms by Site; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Neoplasms; Small Cell Lung Carcinoma; Organic Chemicals; Coordination Complexes; Carboplatin
• Other Study ID Numbers: EC#230766; 2020203 (Other Grant/Funding Number: Clinical therapy research in the specialist health services)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Results, including biomarker analyses, will be made available in Sponsor's data repository based on the data management plan and according to FAIR principles.
• IPD Sharing Time Frame: December 2029
• IPD Sharing Access Criteria: The repository is based on Dataverse, and available for anyone.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No