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

Primary Purpose

Small-cell Lung Cancer

Status
Recruiting
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Thoracic radiotherapy
Chemo-immunotherapy
Sponsored by
Norwegian University of Science and Technology
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Small-cell Lung Cancer focused on measuring cancer, chemotherapy, radiotherapy, immunotherapy

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Rigshospitalet KøbenhavnRecruiting
  • Odense University HospitalRecruiting
  • North Estonia Medical CentreRecruiting
  • Landspitali University HospitalRecruiting
  • Erasmus MCRecruiting
  • Haukeland UniversitetssykehusRecruiting
  • Nordlandssykehuset HFRecruiting
  • Drammen sykehus - Vestre VikenRecruiting
  • Innlandet hospital GjøvikRecruiting
  • Haugesund hospitalRecruiting
  • Sykehuset LevangerRecruiting
  • Akershus Universitetssykehus AHUSRecruiting
  • Oslo University Hospital UllevålRecruiting
  • Stavanger University HospitalRecruiting
  • University Hospital of North Norway, Pulmonology DepartmentRecruiting
  • Cancer Clinic at St. Olavs HospitalRecruiting
  • Ålesund HospitalRecruiting
  • Gävle hospitalRecruiting
  • Sahlgrenska SjukehusetRecruiting
  • Karolinska University HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Chemo-immunotherapy plus thoracic radiotherapy

Chemo-immunotherapy

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

Change in 1-year overall survival
The Cox proportional hazards method will be used to compare survival between the treatment groups.

Secondary Outcome Measures

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.
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.
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.
Change in overall response rates
Response rates are compared using Pearson's Chi-square test.
Change in response rates in non-irradiated lesions
Response rates are compared using Pearson's Chi-square test.
Local control rates in the thorax
Local control rates are compared using Pearson's Chi-square test.
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.

Full Information

First Posted
January 11, 2022
Last Updated
April 21, 2023
Sponsor
Norwegian University of Science and Technology
Collaborators
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, Sykehuset Innlandet HF, North Estonia Medical Centre, Nordlandssykehuset HF, Landspitali University Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT05223647
Brief Title
Chemo-immunotherapy Plus Thoracic Radiotherapy in Extensive Stage Small-cell Lung Cancer
Acronym
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
Study Type
Interventional

2. Study Status

Record Verification Date
April 2023
Overall Recruitment Status
Recruiting
Study Start Date
January 11, 2022 (Actual)
Primary Completion Date
January 2026 (Anticipated)
Study Completion Date
October 2029 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Norwegian University of Science and Technology
Collaborators
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, Sykehuset Innlandet HF, North Estonia Medical Centre, Nordlandssykehuset HF, Landspitali University Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Small-cell Lung Cancer
Keywords
cancer, chemotherapy, radiotherapy, immunotherapy

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
302 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Chemo-immunotherapy plus thoracic radiotherapy
Arm Type
Experimental
Arm Description
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.
Arm Title
Chemo-immunotherapy
Arm Type
Active Comparator
Arm Description
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.
Intervention Type
Procedure
Intervention Name(s)
Thoracic radiotherapy
Intervention Description
30Gy/10 fractions thoracic radiotherapy given between 2nd and 3rd course of chemo-immunotherapy.
Intervention Type
Drug
Intervention Name(s)
Chemo-immunotherapy
Other Intervention Name(s)
carboplatin/etoposide/durvalumab
Intervention Description
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.
Primary Outcome Measure Information:
Title
Change in 1-year overall survival
Description
The Cox proportional hazards method will be used to compare survival between the treatment groups.
Time Frame
14 months after last patient entry
Secondary Outcome Measure Information:
Title
Change in 2-, 3-, 4- and 5-year survival rate
Description
The Cox proportional hazards method will be used to compare survival between the treatment groups.
Time Frame
2, 3, 4 and 5 years after last patient entry
Title
Frequency and severity of adverse events
Description
Adverse events will be compared between the treatment arms using the Pearson's Chi-square and Fisher's exact test.
Time Frame
Through study completion, an average of 1 year after last patient entry
Title
Change in progression free survival (PFS)
Description
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.
Time Frame
Through study completion, an average of 1 year after last patient entry
Title
Change in overall response rates
Description
Response rates are compared using Pearson's Chi-square test.
Time Frame
Through study completion, an average of 1 year after last patient entry
Title
Change in response rates in non-irradiated lesions
Description
Response rates are compared using Pearson's Chi-square test.
Time Frame
Through study completion, an average of 1 year after last patient entry
Title
Local control rates in the thorax
Description
Local control rates are compared using Pearson's Chi-square test.
Time Frame
Through study completion, an average of 1 year after last patient entry
Title
Health-related quality of life (HRQoL)
Description
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.
Time Frame
Through study completion, an average of 1 year after last patient entry
Other Pre-specified Outcome Measures:
Title
Change in cognitive function from baseline to end of treatment
Description
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.
Time Frame
Through study completion, an average of 2 years after last patient entry
Title
Frequency and timing of brain metastases
Description
Changes in brain metastases are compared using Pearson's Chi-square test.
Time Frame
Through study completion, an average of 2 years after last patient entry
Title
Associations between outcomes of study treatment and biomarkers in tissue, blood and stool
Description
A detailed plan for analyses will be defined when sufficient material for translational research has been collected.
Time Frame
Through study completion, an average of 2 years after last patient entry

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Age > 18 years at time of study entry ECOG performance status of 0 or 1 Body weight >30 kg Adequate bone marrow, liver and kidney function Life expectancy of at least 3 months At least one measurable (RECIST 1.1), thoracic lesion that can be irradiated with 30 Gy/10 fractions Histologically or cytologically confirmed SCLC Stage III-IV disease (TNM v8) FEV1 >1 L or >30 % of predicted value and DLCO >30 % of predicted value 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: Previous chemo-, immuno- or radiotherapy for SCLC Major surgical procedure last 28 days History of allogenic organ transplantation, autoimmune disease, immunodeficiency, hepatitis or HIV Uncontrolled intercurrent illness Other active malignancy Leptomeningeal carcinomatosis Immunosuppressive medication Pregnant or breastfeeding women
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Bjørn H Grønberg, MD, PhD
Phone
47297878
Ext
+47
Email
bjorn.h.gronberg@ntnu.no
First Name & Middle Initial & Last Name or Official Title & Degree
Trude C Frøseth, MSc
Email
triplex@stolav.no
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Magnus Steigedal, PhD
Organizational Affiliation
Department of Clinical and Molecular Medicine, NTNU
Official's Role
Study Director
Facility Information:
Facility Name
Rigshospitalet København
City
København
Country
Denmark
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Seppo Langer
Facility Name
Odense University Hospital
City
Odense
Country
Denmark
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Tine Schytte
Facility Name
North Estonia Medical Centre
City
Tallinn
Country
Estonia
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Kersti Oselin
Facility Name
Landspitali University Hospital
City
Reykjavík
Country
Iceland
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Örvar Gunnarsson
Facility Name
Erasmus MC
City
Rotterdam
Country
Netherlands
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Joachim Aerts
Facility Name
Haukeland Universitetssykehus
City
Bergen
Country
Norway
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Marianne Aanerud
Facility Name
Nordlandssykehuset HF
City
Bodø
Country
Norway
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Luka Stanisavljevic, MD
Facility Name
Drammen sykehus - Vestre Viken
City
Drammen
Country
Norway
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Odd Terje Brustugun
Facility Name
Innlandet hospital Gjøvik
City
Gjøvik
Country
Norway
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Daniel Heinrich
Facility Name
Haugesund hospital
City
Haugesund
Country
Norway
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Sverre Fluge
Facility Name
Sykehuset Levanger
City
Levanger
Country
Norway
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Hanne Sorger
Facility Name
Akershus Universitetssykehus AHUS
City
Oslo
Country
Norway
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Kirill Neumann
Facility Name
Oslo University Hospital Ullevål
City
Oslo
Country
Norway
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Maria Moksnes Bjaanes
Facility Name
Stavanger University Hospital
City
Stavanger
Country
Norway
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Madebo Tesfaye
Facility Name
University Hospital of North Norway, Pulmonology Department
City
Tromsø
Country
Norway
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Nina Helbekkmo
Facility Name
Cancer Clinic at St. Olavs Hospital
City
Trondheim
Country
Norway
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Bjørn H Grønberg
Facility Name
Ålesund Hospital
City
Ålesund
Country
Norway
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Øyvind Yksnøy
Facility Name
Gävle hospital
City
Gävle
Country
Sweden
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Johan Isaksson
Facility Name
Sahlgrenska Sjukehuset
City
Göteborg
Country
Sweden
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jan Nyman
Facility Name
Karolinska University Hospital
City
Stockholm
Country
Sweden
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Georgios Tsakonas

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
Results, including biomarker analyses, will be made available in Sponsor's data repository based on the data management plan and according to FAIR principles.
IPD Sharing Time Frame
December 2029
IPD Sharing Access Criteria
The repository is based on Dataverse, and available for anyone.

Learn more about this trial

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

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