Clinical trial NCT02041845: Two Schedules of Hyperfractionated Thoracic Radiotherapy in Limited Disease Small Cell Lung Cancer
Official title: A Randomized Phase II Study Comparing Two Schedules of Hyperfractionated Thoracic Radiotherapy in Limited Disease Small Cell Lung Cancer
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Small Cell Lung Carcinoma
Keywords: Radiotherapy
Radiotherapy dosage
Dose fractionation
Radiotherapy, image-guided
Thorax
Lead sponsor: Norwegian University of Science and Technology
Sponsor class: OTHER
Collaborators: name: St. Olavs Hospital
name: Oslo University Hospital
name: University Hospital of North Norway
name: Sorlandet Hospital HF
First posted: 2014-01-22
Enrollment: 177
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).


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

Primary outcomes:
measure: survival
timeFrame: 2 years
Secondary outcomes:
measure: progression free survival (PFS)
timeFrame: 2 years
measure: Local control
timeFrame: 2 years
measure: overall survival
timeFrame: 3 years
measure: toxicity
timeFrame: 2 years
measure: health related quality of life (HRQoL)
timeFrame: 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:
measure: Exploratory analyses of associations between characteristics and blood biomarkers - and outcomes of therapy
timeFrame: 3 years
Locations:
city: København
country: Denmark
facility: Rigshospitalet København
city: Odense
country: Denmark
facility: Odense University Hospital
city: Bergen
country: Norway
facility: Haukeland Universitetssykehus
city: Drammen
country: Norway
facility: Vestre Viken HF, Drammen Sykehus
city: Førde
country: Norway
facility: Førde Sentralsykehus
city: Gjøvik
country: Norway
facility: Sykehuset Innlandet Gjøvik
city: Haugesund
country: Norway
facility: Haugesund sykehus
city: Levanger
country: Norway
facility: Sykehuset Levanger
city: Namsos
country: Norway
facility: Sykehuset Namsos
city: Oslo
country: Norway
facility: Akershus Universitetssykehus
city: Oslo
country: Norway
facility: Oslo Universitetssykehus, Radiumhospitalet
city: Sarpsborg
country: Norway
facility: Sykehuset Østfold (Kalnes/Sarpsborg)
city: Stavanger
country: Norway
facility: Universitetssjukehuset i Stavanger
city: Tromsø
country: Norway
facility: University Hospital of North Norway, Pulmonology Department
city: Trondheim
country: Norway
facility: Cancer Clinic at St. Olavs Hospital
city: Ålesund
country: Norway
facility: Ålesund sykehus
city: Gävle
country: Sweden
facility: Gävle Sjukhus
city: Göteborg
country: Sweden
facility: Sahlgrenska Sjukehuset
city: Lund
country: Sweden
facility: Skånes universitetssjukhus
city: Stockholm
country: Sweden
facility: Karolinska University Hospital
city: Umeå
country: Sweden
facility: Norrlands Universitetssjukehus
city: Örebro
country: Sweden
facility: Universitetssjukehuset i Ôrebro
Study officials:
affiliation: Norwegian University of Science and Technology
name: Bjørn H Grønberg, md phd
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.