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

Sponsor
Norwegian University of Science and Technology (Other)
Overall Status
Recruiting
CT.gov ID
NCT05223647
Collaborator
St. Olavs Hospital (Other), Haukeland University Hospital (Other), University Hospital of North Norway (Other), Alesund Hospital (Other), Helse Stavanger HF (Other), Oslo University Hospital (Other), Helse Nord-Trøndelag HF (Other), Helse Fonna (Other), Drammen sykehus (Other), University Hospital, Akershus (Other), Odense University Hospital (Other), Rigshospitalet, Denmark (Other), Erasmus Medical Center (Other), Sahlgrenska University Hospital, Sweden (Other), Karolinska University Hospital (Other), Gävle Hospital (Other), National Cancer Institute, Lithuania (Other), Sykehuset Innlandet HF (Other), North Estonia Medical Centre (Other)
302
Enrollment
19
Locations
2
Arms
92.6
Anticipated Duration (Months)
15.9
Patients Per Site
0.2
Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
Phase 3

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 Design

Study Type:
Interventional
Anticipated Enrollment :
302 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
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
Actual Study Start Date :
Jan 11, 2022
Anticipated Primary Completion Date :
Jan 1, 2026
Anticipated Study Completion Date :
Oct 1, 2029

Arms and Interventions

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

    		•

    Outcome Measures

    Primary Outcome Measures

    1. 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 Outcome Measures

    1. 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.

    2. 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.

    3. 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.

    4. 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.

    5. 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.

    6. 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.

    7. 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.

    Other Outcome Measures

    1. Change in cognitive function from baseline to end of treatment [Through study completion, an average of 2 years after last patient entry]

      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.

    2. Frequency and timing of brain metastases [Through study completion, an average of 2 years after last patient entry]

      Changes in brain metastases are compared using Pearson's Chi-square test.

    3. Associations between outcomes of study treatment and biomarkers in tissue, blood and stool [Through study completion, an average of 2 years after last patient entry]

      A detailed plan for analyses will be defined when sufficient material for translational research has been collected.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts 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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Rigshospitalet København København Denmark
    2 Odense University Hospital Odense Denmark
    3 North Estonia Medical Centre Tallinn Estonia
    4 National Cancer Institute Vilnius Lithuania
    5 Erasmus MC Rotterdam Netherlands
    6 Haukeland Universitetssykehus Bergen Norway
    7 Drammen sykehus - Vestre Viken Drammen Norway
    8 Innlandet hospital Gjøvik Gjøvik Norway
    9 Haugesund hospital Haugesund Norway
    10 Sykehuset Levanger Levanger Norway
    11 Akershus Universitetssykehus AHUS Oslo Norway
    12 Oslo University Hospital Ullevål Oslo Norway
    13 Stavanger University Hospital Stavanger Norway
    14 University Hospital of North Norway, Pulmonology Department Tromsø Norway
    15 Cancer Clinic at St. Olavs Hospital Trondheim Norway
    16 Ålesund Hospital Ålesund Norway
    17 Gävle hospital Gävle Sweden
    18 Sahlgrenska Sjukehuset Göteborg Sweden
    19 Karolinska University Hospital Stockholm Sweden

    Sponsors and Collaborators

    • 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
    • Odense University Hospital
    • Rigshospitalet, Denmark
    • Erasmus Medical Center
    • Sahlgrenska University Hospital, Sweden
    • Karolinska University Hospital
    • Gävle Hospital
    • National Cancer Institute, Lithuania
    • Sykehuset Innlandet HF
    • North Estonia Medical Centre

    Investigators

    • Study Director: Magnus Steigedal, PhD, Department of Clinical and Molecular Medicine, NTNU

    Study Documents (Full-Text)

    More Information

    Publications

    None provided.
    Responsible Party:
    Norwegian University of Science and Technology
    ClinicalTrials.gov Identifier:
    NCT05223647
    Other Study ID Numbers:
    • EC#230766
    • 2020203
    First Posted:
    Feb 4, 2022
    Last Update Posted:
    Feb 4, 2022
    Last Verified:
    Feb 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Studies a U.S. FDA-regulated Drug Product:
    No
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Norwegian University of Science and Technology
    cancer
    chemotherapy
    radiotherapy
    immunotherapy
    Additional relevant MeSH terms:
    Lung Neoplasms
    Small Cell Lung Carcinoma
    Carboplatin
    Etoposide
    Durvalumab

    Study Results

    No Results Posted as of Feb 4, 2022