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

NCT ID: NCT02041845

Last Updated: 2025-06-06

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: NA
• Total Enrollment: 177 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-07-08
• Study Completion Date: 2033-12-31

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).

Conditions

Small Cell Lung Carcinoma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

A

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

Group Type: ACTIVE_COMPARATOR

45 Gy in 30 fractions

Intervention Type: RADIATION

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

B

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

Group Type: EXPERIMENTAL

60 Gy in 40 fractions

Intervention Type: RADIATION

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.

Interventions

45 Gy in 30 fractions

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

60 Gy in 40 fractions

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.

Intervention Type: RADIATION

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

St. Olavs Hospital

OTHER

Sponsor Role: collaborator

Oslo University Hospital

OTHER

Sponsor Role: collaborator

University Hospital of North Norway

OTHER

Sponsor Role: collaborator

Sorlandet Hospital HF

OTHER_GOV

Sponsor Role: collaborator

Norwegian University of Science and Technology

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Bjørn H Grønberg, md phd

Role: PRINCIPAL_INVESTIGATOR

Norwegian University of Science and Technology

Locations

Rigshospitalet København

Copenhagen, , Denmark

Odense University Hospital

Odense, , Denmark

Ålesund sykehus

Ålesund, , Norway

Haukeland Universitetssykehus

Bergen, , Norway

Vestre Viken HF, Drammen Sykehus

Drammen, , Norway

Førde Sentralsykehus

Førde, , Norway

Sykehuset Innlandet Gjøvik

Gjøvik, , Norway

Haugesund sykehus

Haugesund, , Norway

Sykehuset Levanger

Levanger, , Norway

Sykehuset Namsos

Namsos, , Norway

Akershus Universitetssykehus

Oslo, , Norway

Oslo Universitetssykehus, Radiumhospitalet

Oslo, , Norway

Sykehuset Østfold (Kalnes/Sarpsborg)

Sarpsborg, , Norway

Universitetssjukehuset i Stavanger

Stavanger, , Norway

University Hospital of North Norway, Pulmonology Department

Tromsø, , Norway

Cancer Clinic at St. Olavs Hospital

Trondheim, , Norway

Gävle Sjukhus

Gävle, , Sweden

Sahlgrenska Sjukehuset

Gothenburg, , Sweden

Skånes universitetssjukhus

Lund, , Sweden

Universitetssjukehuset i Ôrebro

Örebro, , Sweden

Karolinska University Hospital

Stockholm, , Sweden

Norrlands Universitetssjukehus

Umeå, , Sweden

Countries

Denmark; Norway; Sweden

References

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.

Reference Type: RESULT

PMID: 33662285 (View on PubMed)

Gronberg BH, Killingberg KT, Flotten O, Bjaanaes MM, Brustugun OT, Madebo T, Langer SW, Risumlund SL, Schytte T, Helbekkmo N, Neumann K, Yksnoy O, Engleson J, Fluge S, Naustdal T, Giske LE, Nyman J, Tsakonas G, Halvorsen TO. High-Dose Versus Standard-Dose Twice-Daily Thoracic Radiotherapy in Limited-Stage SCLC: Final Survival Data, Long-Term Toxicity, and Relapse Patterns in a Randomized, Open-Label, Phase II Trial. J Thorac Oncol. 2025 Aug;20(8):1108-1119. doi: 10.1016/j.jtho.2025.04.007. Epub 2025 Apr 19.

Reference Type: DERIVED

PMID: 40258573 (View on PubMed)

Taranova E, Aanerud M, Halvorsen TO, Killingberg KT, Slaaen M, Gronberg BH. Associations Between Patient-Reported Nutritional Status, Toxicity, and Survival in Limited-Stage SCLC. JTO Clin Res Rep. 2024 Nov 12;6(1):100764. doi: 10.1016/j.jtocrr.2024.100764. eCollection 2025 Jan.

Reference Type: DERIVED

PMID: 39802818 (View on PubMed)

Killingberg KT, Gronberg BH, Slaaen M, Kirkevold O, Halvorsen TO. Treatment Outcomes of Older Participants in a Randomized Trial Comparing Two Schedules of Twice-Daily Thoracic Radiotherapy in Limited-Stage SCLC. J Thorac Oncol. 2023 Jun;18(6):803-812. doi: 10.1016/j.jtho.2023.01.012. Epub 2023 Jan 27.

Reference Type: DERIVED

PMID: 36716960 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 35183991 (View on PubMed)

Other Identifiers

2013/2163

Identifier Type: -

Identifier Source: org_study_id