Small-cell Lung Cancer
Conditions
Keywords
cancer, chemotherapy, radiotherapy, immunotherapy
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.
Interventions
PROCEDUREThoracic radiotherapy
30Gy/10 fractions thoracic radiotherapy given between 2nd and 3rd course of 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.
Sponsors
Norwegian University of Science and Technology
St. Olavs Hospital
Haukeland University Hospital
University Hospital of North Norway
Alesund Hospital
Helse Stavanger HF
Oslo University Hospital
Helse Nord-Trøndelag HF
Helse Fonna
Drammen sykehus
University Hospital, Akershus
Erasmus Medical Center
Sahlgrenska University Hospital
Karolinska University Hospital
Gävle Hospital
Sykehuset Innlandet HF
North Estonia Medical Centre
Nordlandssykehuset HF
Landspitali University Hospital
Lund University Hospital
University Hospital, Linkoeping
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 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 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. |
| 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. |
| 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. |
| 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. |
Countries
Estonia, Iceland, Netherlands, Norway, Sweden
Contacts
STUDY_DIRECTORMagnus Steigedal, PhD
Department of Clinical and Molecular Medicine, NTNU
Outcome results
None listed