Not provided
| ID | Type | Description | Link |
|---|---|---|---|
| 2020203 | Other Grant/Funding Number | Clinical therapy research in the specialist health services |
Not provided
Not provided
Termination was adviced by Data Safety Committee due to excess toxicity of the experimental treatment.
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Class |
|---|---|
| St. Olavs Hospital | OTHER |
| Haukeland University Hospital | OTHER |
| University Hospital of North Norway | OTHER |
| Alesund Hospital |
Not provided
Not provided
Not provided
Not provided
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.
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.
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Chemo-immunotherapy plus thoracic radiotherapy | Experimental | 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 | Active Comparator | 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Thoracic radiotherapy | Procedure | 30Gy/10 fractions thoracic radiotherapy given between 2nd and 3rd course of chemo-immunotherapy. |
|
| 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 |
| 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 |
| 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 |
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Magnus Steigedal, PhD | Department of Clinical and Molecular Medicine, NTNU | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| North Estonia Medical Centre | Tallinn | Estonia | ||||
| Landspitali University Hospital |
Results, including biomarker analyses, will be made available in Sponsor's data repository based on the data management plan and according to FAIR principles.
December 2029
The repository is based on Dataverse, and available for anyone.
Not provided
Not provided
| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Jan 5, 2022 | Jan 25, 2022 |
| OTHER |
| Helse Stavanger HF | OTHER_GOV |
| Oslo University Hospital | OTHER |
| Helse Nord-Trøndelag HF | OTHER |
| Helse Fonna | OTHER |
| Drammen sykehus | OTHER |
| University Hospital, Akershus | OTHER |
| Erasmus Medical Center | OTHER |
| Sahlgrenska University Hospital | OTHER |
| Karolinska University Hospital | OTHER |
| Gävle Hospital | OTHER |
| Sykehuset Innlandet HF | OTHER |
| North Estonia Medical Centre | OTHER |
| Nordlandssykehuset HF | OTHER |
| Landspitali University Hospital | OTHER |
| Lund University Hospital | OTHER |
| University Hospital, Linkoeping | OTHER |
Not provided
Not provided
Not provided
Not provided
Not provided
| Chemo-immunotherapy | Drug | 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. |
|
|
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 |
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 |
| Reykjavik |
| Iceland |
| Erasmus MC | Rotterdam | Netherlands |
| 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 | Norway |
| Gävle hospital | Gävle | Sweden |
| Sahlgrenska Sjukehuset | Gothenburg | Sweden |
| Linköping University Hospital | Linköping | Sweden |
| Lund University Hospital | Skåne | Sweden |
| Karolinska University Hospital | Stockholm | Sweden |
| Prot_000.pdf |
| ICF | No | No | Yes | Informed Consent Form | Dec 21, 2021 | Jan 25, 2022 | ICF_001.pdf |
| ID | Term |
|---|---|
| D055752 | Small Cell Lung Carcinoma |
| D009369 | Neoplasms |
| ID | Term |
|---|---|
| D002283 | Carcinoma, Bronchogenic |
| D001984 | Bronchial Neoplasms |
| D008175 | Lung Neoplasms |
| D012142 | Respiratory Tract Neoplasms |
| D013899 | Thoracic Neoplasms |
| D009371 | Neoplasms by Site |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| D016190 | Carboplatin |
| ID | Term |
|---|---|
| D056831 | Coordination Complexes |
| D009930 | Organic Chemicals |
Not provided
Not provided