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

NCT02041845 | Active Not Recruiting

• 1 other identifier: 2013/2163
• Study Type: interventional
• Target: 177
• Locations: 3 countries
• Sites: 22

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

Keywords

Radiotherapy; Radiotherapy dosage; Dose fractionation; Radiotherapy, image-guided; Thorax

Outcome Measures

Primary Outcomes (1)

• 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).

  2 years

Secondary Outcomes (5)

• progression free survival (PFS)

  2 years

• Local control

  2 years

• overall survival

  3 years

• toxicity

  2 years

• health related quality of life (HRQoL)

  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 Outcomes (1)

• Exploratory analyses of associations between characteristics and blood biomarkers - and outcomes of therapy

  3 years

Study Arms (2)

A

ACTIVE COMPARATOR

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

Radiation: 45 Gy in 30 fractions

B

EXPERIMENTAL

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

Radiation: 60 Gy in 40 fractions

Interventions

45 Gy in 30 fractions RADIATION

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

A

60 Gy in 40 fractions 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.

B

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Norwegian University of Science and Technology: lead
• St. Olavs Hospital: collaborator
• Oslo University Hospital: collaborator
• University Hospital of North Norway: collaborator
• Sorlandet Hospital HF: collaborator

Study Sites (22)

Rigshospitalet København

Copenhagen, Denmark

Location

Odense University Hospital

Odense, Denmark

Location

Ålesund sykehus

Ålesund, Norway

Location

Haukeland Universitetssykehus

Bergen, Norway

Location

Vestre Viken HF, Drammen Sykehus

Drammen, Norway

Location

Førde Sentralsykehus

Førde, Norway

Location

Sykehuset Innlandet Gjøvik

Gjøvik, Norway

Location

Haugesund sykehus

Haugesund, Norway

Location

Sykehuset Levanger

Levanger, Norway

Location

Sykehuset Namsos

Namsos, Norway

Location

Akershus Universitetssykehus

Oslo, Norway

Location

Oslo Universitetssykehus, Radiumhospitalet

Oslo, Norway

Location

Sykehuset Østfold (Kalnes/Sarpsborg)

Sarpsborg, Norway

Location

Universitetssjukehuset i Stavanger

Stavanger, Norway

Location

University Hospital of North Norway, Pulmonology Department

Tromsø, Norway

Location

Cancer Clinic at St. Olavs Hospital

Trondheim, Norway

Location

Gävle Sjukhus

Gävle, Sweden

Location

Sahlgrenska Sjukehuset

Gothenburg, Sweden

Location

Skånes universitetssjukhus

Lund, Sweden

Location

Universitetssjukehuset i Ôrebro

Örebro, Sweden

Location

Karolinska University Hospital

Stockholm, Sweden

Location

Norrlands Universitetssjukehus

Umeå, Sweden

Location

Related Publications (5)

• 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.

  PMID: 33662285 RESULT

• 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.

  PMID: 40258573 DERIVED

• 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.

  PMID: 39802818 DERIVED

• 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.

  PMID: 36716960 DERIVED

• 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.

  PMID: 35183991 DERIVED

MeSH Terms

Conditions

Small Cell Lung Carcinoma

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Bjørn H Grønberg, md phd

  Norwegian University of Science and Technology

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 14, 2014
• First Posted: January 22, 2014
• Study Start: July 8, 2014
• Primary Completion: July 29, 2020
• Study Completion (Estimated): December 31, 2033
• Last Updated: June 6, 2025

Record last verified: 2025-06

Locations

SE (6); NO (14); DK (2)