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Two Schedules of Hyperfractionated Thoracic Radiotherapy in Limited Disease Small Cell Lung Cancer (THORA)

Primary Purpose

Small Cell Lung Carcinoma

Status
Active
Phase
Not Applicable
Locations
International
Study Type
Interventional
Intervention
45 Gy in 30 fractions
60 Gy in 40 fractions
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 Carcinoma focused on measuring Radiotherapy, Radiotherapy dosage, Dose fractionation, Radiotherapy, image-guided, Thorax

Eligibility Criteria

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

Inclusion Criteria:

  • Histologically or cytologically confirmed small-cell lung cancer (SCLC)
  • Limited disease (stage II-III)
  • Stage I if ineligible for surgery
  • Eastern Cooperative Oncology Group (ECOG) Performance 0-2
  • Measureable disease according to the Response Evaluation Criteria In Solid Tumors (RECIST) 1.1
  • Adequate organ function defined as: (a) Serum serum alanine transaminase (ALT) ≤ 3 x upper limit of normal (ULN); (b) Total serum bilirubin ≤ 1.5 x ULN; (c) Absolute neutrophil count (ANC) ≥ 1.5 x 109/L; (d) Platelets ≥ 100 x 109/L; (e) Creatinine < 100 µmol/L and calculated creatinine-clearance > 50 ml/min. If calculated creatinine-clearance is < 50 ml/min, an ethylene diamine tetra-acetic acid (EDTA) clearance should be performed.
  • Pulmonary function: Forced Expiratory Volume in One Second (FEV1) > 1 l or 30 % of predicted value and diffusing capacity of the lungs for carbon monoxide (DLCO) > 30 % of predicted value
  • All fertile patients should use safe contraception
  • Written informed consent

Exclusion Criteria:

  • prior systemic therapy for small-cell lung cancer
  • Previous radiotherapy to the thorax
  • malignant cells in pericardial or pleural fluid (at least one sample should be analysed if pleural fluid is present
  • serious concomitant systemic disorders (for example active infection, unstable cardiovascular disease) that in the opinion of the investigator would compromise the patient's ability to complete the study or interfere with the evaluation of the efficacy and safety of the study treatment
  • conditions - medical, social, psychological - which could prevent adequate information and follow-up
  • clinically active cancer other than SCLC. Hormonal therapy for prostate cancer or breast cancer and basocellular carcinoma of the skin is allowed
  • pregnancy, lactation

Sites / Locations

  • Rigshospitalet København
  • Odense University Hospital
  • Haukeland Universitetssykehus
  • Vestre Viken HF, Drammen Sykehus
  • Førde Sentralsykehus
  • Sykehuset Innlandet Gjøvik
  • Haugesund sykehus
  • Sykehuset Levanger
  • Sykehuset Namsos
  • Akershus Universitetssykehus
  • Oslo Universitetssykehus, Radiumhospitalet
  • Sykehuset Østfold (Kalnes/Sarpsborg)
  • Universitetssjukehuset i Stavanger
  • University Hospital of North Norway, Pulmonology Department
  • Cancer Clinic at St. Olavs Hospital
  • Ålesund sykehus
  • Gävle Sjukhus
  • Sahlgrenska Sjukehuset
  • Skånes universitetssjukhus
  • Karolinska University Hospital
  • Norrlands Universitetssjukehus
  • Universitetssjukehuset i Ôrebro

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

A

B

Arm Description

3D conformal thoracic radiotherapy at a total dose of 45 Gy in 30 fractions, 2 fractions per day, 5 days a week

3D conformal thoracic radiotherapy at a total dose of 60 Gy in 40 fractions, 2 fractions per day, 5 days a week

Outcomes

Primary Outcome Measures

survival
measured for all patients from the date of the first day of the first course of chemotherapy until the date of death from any cause (or last contact/observation if lost to follow-up - or the follow-up is completed before all patients die).

Secondary Outcome Measures

progression free survival (PFS)
measured for all patients from the date of the first day of the first course of PE to the first date of objective progression (according to RECIST 1.1) of disease or of death from any cause. For each patient who has not died or has non-progression at the cut-off date for the analysis, PFS will be censored at the date of the patient's last tumor assessment prior to the cut-off date. Statistical survival analyses will be done with Kaplan Meier. Log rank test will be used for comparing groups.
Local control
Proportion of all patients who experience disease recurrence within radiotherapy fields assessed by comparing dose plans and follow-up CT scans.
overall survival
measured for all patients from the date of the first day of the first course of chemotherapy until the date of death from any cause (or last contact/observation if lost to follow-up - or the follow-up is completed before all patients die).
toxicity
assessed for all patients receiving at least one course of chemotherapy from reported blood values and adverse event. Classified and graded according to CTCAE 4.0. Compared using Pearson's Chi-square and Fischer's exact tests.
health related quality of life (HRQoL)
assessed from completed questionnaires. Patients will report HRQoL on the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ) C30 and the lung cancer specific module LC13. The QLQ-C30 measures fundamental aspects of HRQoL and symptoms commonly reported by cancer patients in general, the LC13 measures symptoms commonly associated with lung cancer and its treatment. All HRQoL scores will be transformed to a scale from 0 to 100 according to the EORTC scoring manual. A difference in mean scores of >10 is considered clinically relevant. For group comparisons of baseline scores during and after chemotherapy, and changes in scores from baseline, the Mann-Whitney test will be used. Primary HRQoL-endpoints are dysphagia and dyspnea.

Full Information

First Posted
January 14, 2014
Last Updated
September 16, 2022
Sponsor
Norwegian University of Science and Technology
Collaborators
St. Olavs Hospital, Oslo University Hospital, University Hospital of North Norway, Sorlandet Hospital HF
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1. Study Identification

Unique Protocol Identification Number
NCT02041845
Brief Title
Two Schedules of Hyperfractionated Thoracic Radiotherapy in Limited Disease Small Cell Lung Cancer
Acronym
THORA
Official Title
A Randomized Phase II Study Comparing Two Schedules of Hyperfractionated Thoracic Radiotherapy in Limited Disease Small Cell Lung Cancer
Study Type
Interventional

2. Study Status

Record Verification Date
September 2022
Overall Recruitment Status
Active, not recruiting
Study Start Date
July 8, 2014 (Actual)
Primary Completion Date
July 29, 2020 (Actual)
Study Completion Date
July 29, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Norwegian University of Science and Technology
Collaborators
St. Olavs Hospital, Oslo University Hospital, University Hospital of North Norway, Sorlandet Hospital HF

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
The majority of patients with limited disease small cell lung cancer (SCLC) experience recurrent disease despite receiving concurrent chemoradiotherapy. New agents and dose-escalation of chemotherapy have not provided a survival benefit. Local failure accounts for high proportion of recurrences. Improved thoracic radiotherapy (TRT) might increase local control and thus reduce the recurrence rate and prolong survival. Positron emission tomography (PET CT) is better for staging of SCLC than computer tomography (CT) and bone scan. More precise localization of tumors leads to more accurate definition of target volumes for TRT and reduce the radiation dose to normal tissue. A large proportion of patients relapse and die within one and two year after therapy. Few patients survive longer than three years. Thus, two-year survival is considered a clinically highly relevant measure of efficacy. The aim of this study is to compare two schedules of TRT with respect to local control, progression free survival, overall survival, toxicity and health-related quality of life. In addition patients who have the best outcomes and tolerate chemoradiotherapy will be characterized (e.g. clinical characteristics, blood biomarkers, body composition).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Small Cell Lung Carcinoma
Keywords
Radiotherapy, Radiotherapy dosage, Dose fractionation, Radiotherapy, image-guided, Thorax

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
177 (Actual)

8. Arms, Groups, and Interventions

Arm Title
A
Arm Type
Active Comparator
Arm Description
3D conformal thoracic radiotherapy at a total dose of 45 Gy in 30 fractions, 2 fractions per day, 5 days a week
Arm Title
B
Arm Type
Experimental
Arm Description
3D conformal thoracic radiotherapy at a total dose of 60 Gy in 40 fractions, 2 fractions per day, 5 days a week
Intervention Type
Radiation
Intervention Name(s)
45 Gy in 30 fractions
Intervention Description
3D conformal thoracic radiotherapy at a total dose of 45 Gy in 30 fractions, 2 fractions per day, 5 days a week
Intervention Type
Radiation
Intervention Name(s)
60 Gy in 40 fractions
Intervention Description
3D conformal thoracic radiotherapy at a total dose of 60 Gy in 40 fractions, 2 fractions per day, 5 days a week. If doses to organs at risk exceed normal tissue tolerance, the dose may be lowered to a minimum of 54 Gy.
Primary Outcome Measure Information:
Title
survival
Description
measured for all patients from the date of the first day of the first course of chemotherapy until the date of death from any cause (or last contact/observation if lost to follow-up - or the follow-up is completed before all patients die).
Time Frame
2 years
Secondary Outcome Measure Information:
Title
progression free survival (PFS)
Description
measured for all patients from the date of the first day of the first course of PE to the first date of objective progression (according to RECIST 1.1) of disease or of death from any cause. For each patient who has not died or has non-progression at the cut-off date for the analysis, PFS will be censored at the date of the patient's last tumor assessment prior to the cut-off date. Statistical survival analyses will be done with Kaplan Meier. Log rank test will be used for comparing groups.
Time Frame
2 years
Title
Local control
Description
Proportion of all patients who experience disease recurrence within radiotherapy fields assessed by comparing dose plans and follow-up CT scans.
Time Frame
2 years
Title
overall survival
Description
measured for all patients from the date of the first day of the first course of chemotherapy until the date of death from any cause (or last contact/observation if lost to follow-up - or the follow-up is completed before all patients die).
Time Frame
3 years
Title
toxicity
Description
assessed for all patients receiving at least one course of chemotherapy from reported blood values and adverse event. Classified and graded according to CTCAE 4.0. Compared using Pearson's Chi-square and Fischer's exact tests.
Time Frame
2 years
Title
health related quality of life (HRQoL)
Description
assessed from completed questionnaires. Patients will report HRQoL on the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ) C30 and the lung cancer specific module LC13. The QLQ-C30 measures fundamental aspects of HRQoL and symptoms commonly reported by cancer patients in general, the LC13 measures symptoms commonly associated with lung cancer and its treatment. All HRQoL scores will be transformed to a scale from 0 to 100 according to the EORTC scoring manual. A difference in mean scores of >10 is considered clinically relevant. For group comparisons of baseline scores during and after chemotherapy, and changes in scores from baseline, the Mann-Whitney test will be used. Primary HRQoL-endpoints are dysphagia and dyspnea.
Time Frame
From baseline, before and after radiotherapy and then at follow-up every 3 months until 24 months after start of chemotherapy. Then every 6 months until 5 year after start of therapy
Other Pre-specified Outcome Measures:
Title
Exploratory analyses of associations between characteristics and blood biomarkers - and outcomes of therapy
Description
All patients will be included in these analyses. Blood will be collected, the study group will define which markers to analyze when all patients have been enrolled.
Time Frame
3 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Histologically or cytologically confirmed small-cell lung cancer (SCLC) Limited disease (stage II-III) Stage I if ineligible for surgery Eastern Cooperative Oncology Group (ECOG) Performance 0-2 Measureable disease according to the Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 Adequate organ function defined as: (a) Serum serum alanine transaminase (ALT) ≤ 3 x upper limit of normal (ULN); (b) Total serum bilirubin ≤ 1.5 x ULN; (c) Absolute neutrophil count (ANC) ≥ 1.5 x 109/L; (d) Platelets ≥ 100 x 109/L; (e) Creatinine < 100 µmol/L and calculated creatinine-clearance > 50 ml/min. If calculated creatinine-clearance is < 50 ml/min, an ethylene diamine tetra-acetic acid (EDTA) clearance should be performed. Pulmonary function: Forced Expiratory Volume in One Second (FEV1) > 1 l or 30 % of predicted value and diffusing capacity of the lungs for carbon monoxide (DLCO) > 30 % of predicted value All fertile patients should use safe contraception Written informed consent Exclusion Criteria: prior systemic therapy for small-cell lung cancer Previous radiotherapy to the thorax malignant cells in pericardial or pleural fluid (at least one sample should be analysed if pleural fluid is present serious concomitant systemic disorders (for example active infection, unstable cardiovascular disease) that in the opinion of the investigator would compromise the patient's ability to complete the study or interfere with the evaluation of the efficacy and safety of the study treatment conditions - medical, social, psychological - which could prevent adequate information and follow-up clinically active cancer other than SCLC. Hormonal therapy for prostate cancer or breast cancer and basocellular carcinoma of the skin is allowed pregnancy, lactation
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Bjørn H Grønberg, md phd
Organizational Affiliation
Norwegian University of Science and Technology
Official's Role
Principal Investigator
Facility Information:
Facility Name
Rigshospitalet København
City
København
Country
Denmark
Facility Name
Odense University Hospital
City
Odense
Country
Denmark
Facility Name
Haukeland Universitetssykehus
City
Bergen
Country
Norway
Facility Name
Vestre Viken HF, Drammen Sykehus
City
Drammen
Country
Norway
Facility Name
Førde Sentralsykehus
City
Førde
Country
Norway
Facility Name
Sykehuset Innlandet Gjøvik
City
Gjøvik
Country
Norway
Facility Name
Haugesund sykehus
City
Haugesund
Country
Norway
Facility Name
Sykehuset Levanger
City
Levanger
Country
Norway
Facility Name
Sykehuset Namsos
City
Namsos
Country
Norway
Facility Name
Akershus Universitetssykehus
City
Oslo
Country
Norway
Facility Name
Oslo Universitetssykehus, Radiumhospitalet
City
Oslo
Country
Norway
Facility Name
Sykehuset Østfold (Kalnes/Sarpsborg)
City
Sarpsborg
Country
Norway
Facility Name
Universitetssjukehuset i Stavanger
City
Stavanger
Country
Norway
Facility Name
University Hospital of North Norway, Pulmonology Department
City
Tromsø
Country
Norway
Facility Name
Cancer Clinic at St. Olavs Hospital
City
Trondheim
Country
Norway
Facility Name
Ålesund sykehus
City
Ålesund
Country
Norway
Facility Name
Gävle Sjukhus
City
Gävle
Country
Sweden
Facility Name
Sahlgrenska Sjukehuset
City
Göteborg
Country
Sweden
Facility Name
Skånes universitetssjukhus
City
Lund
Country
Sweden
Facility Name
Karolinska University Hospital
City
Stockholm
Country
Sweden
Facility Name
Norrlands Universitetssjukehus
City
Umeå
Country
Sweden
Facility Name
Universitetssjukehuset i Ôrebro
City
Örebro
Country
Sweden

12. IPD Sharing Statement

Citations:
PubMed Identifier
35183991
Citation
Killingberg KT, Halvorsen TO, Flotten O, Brustugun OT, Langer SW, Nyman J, Hornslien K, Madebo T, Schytte T, Risum S, Tsakonas G, Engleson J, Gronberg BH. Patient-reported health-related quality of life from a randomized phase II trial comparing standard-dose with high-dose twice daily thoracic radiotherapy in limited stage small-cell lung cancer. Lung Cancer. 2022 Apr;166:49-57. doi: 10.1016/j.lungcan.2022.02.002. Epub 2022 Feb 8.
Results Reference
derived
PubMed Identifier
33662285
Citation
Gronberg BH, Killingberg KT, Flotten O, Brustugun OT, Hornslien K, Madebo T, Langer SW, Schytte T, Nyman J, Risum S, Tsakonas G, Engleson J, Halvorsen TO. High-dose versus standard-dose twice-daily thoracic radiotherapy for patients with limited stage small-cell lung cancer: an open-label, randomised, phase 2 trial. Lancet Oncol. 2021 Mar;22(3):321-331. doi: 10.1016/S1470-2045(20)30742-7.
Results Reference
derived

Learn more about this trial

Two Schedules of Hyperfractionated Thoracic Radiotherapy in Limited Disease Small Cell Lung Cancer

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