Clinical trial NCT05223647: Chemo-immunotherapy Plus Thoracic Radiotherapy in Extensive Stage Small-cell Lung Cancer
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Small-cell Lung Cancer
Keywords: cancer
chemotherapy
radiotherapy
immunotherapy
Lead sponsor: Norwegian University of Science and Technology
Sponsor class: OTHER
Collaborators: name: St. Olavs Hospital
name: Haukeland University Hospital
name: University Hospital of North Norway
name: Alesund Hospital
name: Helse Stavanger HF
name: Oslo University Hospital
name: Helse Nord-Trøndelag HF
name: Helse Fonna
name: Drammen sykehus
name: University Hospital, Akershus
name: Erasmus Medical Center
name: Sahlgrenska University Hospital
name: Karolinska University Hospital
name: Gävle Hospital
name: Sykehuset Innlandet HF
name: North Estonia Medical Centre
name: Nordlandssykehuset HF
name: Landspitali University Hospital
name: Lund University Hospital
name: University Hospital, Linkoeping
First posted: 2022-02-04
Enrollment: 302
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Change in 1-year overall survival
timeFrame: 14 months after last patient entry
Secondary outcomes:
measure: Change in 2-, 3-, 4- and 5-year survival rate
timeFrame: 2, 3, 4 and 5 years after last patient entry
measure: Frequency and severity of adverse events
timeFrame: Through study completion, an average of 1 year after last patient entry
measure: Change in progression free survival (PFS)
timeFrame: Through study completion, an average of 1 year after last patient entry
measure: Change in overall response rates
timeFrame: Through study completion, an average of 1 year after last patient entry
measure: Change in response rates in non-irradiated lesions
timeFrame: Through study completion, an average of 1 year after last patient entry
measure: Local control rates in the thorax
timeFrame: Through study completion, an average of 1 year after last patient entry
measure: Health-related quality of life (HRQoL)
timeFrame: Through study completion, an average of 1 year after last patient entry
Other outcomes:
measure: Change in cognitive function from baseline to end of treatment
timeFrame: Through study completion, an average of 2 years after last patient entry
measure: Frequency and timing of brain metastases
timeFrame: Through study completion, an average of 2 years after last patient entry
measure: Associations between outcomes of study treatment and biomarkers in tissue, blood and stool
timeFrame: Through study completion, an average of 2 years after last patient entry
Locations:
city: Tallinn
country: Estonia
facility: North Estonia Medical Centre
city: Reykjavík
country: Iceland
facility: Landspitali University Hospital
city: Rotterdam
country: Netherlands
facility: Erasmus MC
city: Bergen
country: Norway
facility: Haukeland Universitetssykehus
city: Bodø
country: Norway
facility: Nordlandssykehuset HF
city: Drammen
country: Norway
facility: Drammen sykehus - Vestre Viken
city: Gjøvik
country: Norway
facility: Innlandet hospital Gjøvik
city: Haugesund
country: Norway
facility: Haugesund hospital
city: Levanger
country: Norway
facility: Sykehuset Levanger
city: Oslo
country: Norway
facility: Akershus Universitetssykehus AHUS
city: Oslo
country: Norway
facility: Oslo University Hospital Ullevål
city: Stavanger
country: Norway
facility: Stavanger University Hospital
city: Tromsø
country: Norway
facility: University Hospital of North Norway, Pulmonology Department
city: Trondheim
country: Norway
facility: Cancer Clinic at St. Olavs Hospital
city: Ålesund
country: Norway
facility: Ålesund Hospital
city: Gävle
country: Sweden
facility: Gävle hospital
city: Göteborg
country: Sweden
facility: Sahlgrenska Sjukehuset
city: Linköping
country: Sweden
facility: Linköping University Hospital
city: Skåne
country: Sweden
facility: Lund University Hospital
city: Stockholm
country: Sweden
facility: Karolinska University Hospital
Study officials:
affiliation: Department of Clinical and Molecular Medicine, NTNU
name: Magnus Steigedal, PhD
role: STUDY_DIRECTOR
References: