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

Small-cell Lung Cancer Clinical Trial

— TRIPLEX  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05223647
• Other study ID #: EC#230766
• Secondary ID: 2020203
• Status: Recruiting
• Phase: Phase 3
• Start date: January 11, 2022
• Est. completion date: October 2029

Study information

• Verified date: January 2024
• Source: Norwegian University of Science and Technology
• Contact: Bjørn H Grønberg, MD, PhD
• Phone: 47297878
• Email: bjorn.h.gronberg[@]ntnu.no
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 302
• Est. completion date: October 2029
• Est. primary completion date: January 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Lung Neoplasms
• Small Cell Lung Carcinoma
• Small-cell Lung Cancer

Intervention

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.

Locations

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

Sponsors (21)

Lead Sponsor

Collaborator

Norwegian University of Science and Technology

Alesund Hospital, Drammen sykehus, Erasmus Medical Center, Gävle Hospital, Haukeland University Hospital, Helse Fonna, Helse Nord-Trøndelag HF, Helse Stavanger HF, Karolinska University Hospital, Landspitali University Hospital, Lund University Hospital, Nordlandssykehuset HF, North Estonia Medical Centre, Oslo University Hospital, Sahlgrenska University Hospital, Sweden, St. Olavs Hospital, Sykehuset Innlandet HF, University Hospital of North Norway, University Hospital, Akershus, University Hospital, Linkoeping

Countries where clinical trial is conducted

Estonia,  Iceland,  Netherlands,  Norway,  Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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
Other	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
Other	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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