Condition category
Cancer
Date applied
20/12/2005
Date assigned
20/12/2005
Last edited
23/10/2007
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

Contact information

Type

Scientific

Primary contact

Dr G.W.P.M. Kramer

ORCID ID

Contact details

Arnhems Radiotherapeutisch Instituut
Wagnerlaan 47
Arnhem
6815 AD
Netherlands
+31 (0)26 371 2493
g.kramer@arnhemrti.nl

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

N/A

Study information

Scientific title

Acronym

0G98/009 LUNGTRIAL

Study hypothesis

The treatment of Non-Small-Cell-Lung-Cancer (NSCLC) is still a challenge for the oncologist. In the last decade combined modality treatment in stage III and chemotherapy in stage IV improved the survival and quality of life (QOL) in NSCLC patients. Unfortunately a vast majority of patients will not be fit enough to undergo these intensive treatments, and those who underwent chemotherapy as palliative treatment may eventually still suffer from loco-regional complaints.

In general, hemoptysis, chest pain, dysphagia, and dyspnoea can all be effectively palliated with acceptable toxicity with all kinds of different radiation treatment schemes. The effectiveness of these different treatment schemes however varies for each different symptom and is most effective for hemoptysis and chest pain in patients with an Eastern Cooperative Oncology Group (ECOG) grade status of 2 - 3. Which dose should be given is still controversial.

In the first Medical Research Council (MRC) trial reported in 1991 no differences in palliative effect and in survival were seen between 13 x 3 Gy and 2 x 8.5 Gy. In a second MRC study in 1992 for poor prognostic patients only, no differences in palliation or survival were seen between 10 Gy single dose and 2 x 8.5 Gy. However in a study by Bezjak et al. a difference in survival between 20 Gy in 5 fractions and a 10 Gy single dose was demonstrated in favour of the multi-fractionation treatment. In a group-analysis, however, this survival advantage was not seen in patients with an ECOG score of 2 or more. Later data suggested a survival advantage of 13 x 3 Gy over 2 x 8.5 Gy in patients with good performance status.

For patients in a bad general condition it still has to be proven whether 2 x 8.5 Gy is equally effective as 10 x 3 Gy. Based on these findings radiation oncologists in the Netherlands could not reach consensus on the appropriate fractionation schedule for palliative irradiation of bad prognosis NSCLC patients. The presented study therefore was focused on patients with bad general condition and/or significant weight loss with stage III NSCLC or stage IV patients, not suitable for chemotherapy, comparing 10 x 3 Gy with 2 x 8 Gy.

Purpose:
This multicentre randomised National Study compared the efficacy of 2 x 8 Gy versus our standard 10 x 3 Gy in patients with inoperable stage IIIA/B (with ECOG score 2 - 4 and/or substantial weight loss) and stage IV Non-Small-Cell Lung Cancer (NSCLC).

Hypothesis:
We expected both treatment arms to have an equal outcome for palliation as for prognosis, because of the above-mentioned results of the MRC studies.

Ethics approval

Ethics approval received from the local medical ethics committee

Study design

Multicentre, randomsied, active controlled, parallel group trial.

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Not specified

Trial type

Treatment

Patient information sheet

Condition

Non Small Cell Lung Cancer (NSCLC)

Intervention

Patients were randomised, without stratification, either to the multiple fractionation scheme of 10 x 3 Gy, 4 - 5 times a week, or the hypo fractionation scheme of 2 x 8 Gy, given at day 1 and day 8.

Irradiation was given with two opposing anterior-posterior fields with 6 - 18 MV photon beams. The treatment portals encompassed the tumour with a margin of 1.5 - 2 cm including adjacent pathological lymph nodes. No limitations were set for the Target Volume. Dose calculation was not corrected for tissue inhomogeneities. Co-medication, including corticosteroids and analgetics, and extra oxygen supply were allowed and registered.

Intervention type

Other

Phase

Not Specified

Drug names

Primary outcome measures

Palliation of thoracic symptoms measured over 52 weeks after randomisation. A maximum of 33 questionnaires per patient would be sent in case follow-up could be completed. The first questionnaire was given before randomisation, the last questionnaire in the 52nd week after randomisation. Data about effectiveness of the treatment and QOL were based on the Rotterdam Symptom Checklist. Seven symptoms could be scored each on a four point validated scale from 1 (no complaints) to 4 (severe complaints). The baseline total symptom score had to be 8 indicating that the patient had at least one tumour related complaint. The maximum total symptom score could be 28 indicating the patient had all seven complaints in the worst degree. After response the lowest total symptom score could be 7, having no complaints at all. Palliation was defined as a average total score below the baseline score.

Secondary outcome measures

1. Toxicity, Quality of Life (QOL), and survival
2. Quality of life was measured using the EuroQol classification system (EQ-5D), consisting of five questions on mobility, self-care, usual activities, pain/discomfort, and anxiety/depression
3. In addition, information about acute toxicity as nausea, vomiting, and radiation oesophagitis induced dysphagia was collected, based on the of the National Cancer Institute of Canada Expanded Clinical Trials Group (NCIC CTG) Common Toxicity Criteria
4. Patients were also asked to provide information about costs. Together with quality of life data, these data will be published separately in a cost-utility analysis
5. Follow up after 52 weeks was continued by the data manager, who made 3-monthly inquiries after survival of the patient

Overall trial start date

01/01/1999

Overall trial end date

31/05/2002

Reason abandoned

Eligibility

Participant inclusion criteria

1. Diagnosis of NSCLC had to be cytologically or histologically confirmed
2. Tumour stage was IIIA or IIIB in combination with performance status 3 – 4 and/or a weight loss of more than 5% in 3 months or greater than 10% in 6 months prior to diagnosis
3. Stage IV NSCLC, not suitable for chemotherapeutic treatment
4. A minimum total symptom score of 8, indicating a score greater than 1 for at least one of the following complaints caused by the tumour itself:
4.1. Loss of appetite
4.2. Dyspnoea
4.3. Chest pain
4.4. Coughing
4.5. Hemoptysis
4.6. Hoarseness and/or dysphagia
5. Physically and mentally fit enough to participate in the study

Participant type

Patient

Age group

Not Specified

Gender

Not Specified

Target number of participants

303

Participant exclusion criteria

1. Superior Vena Cava Syndrome (SVCS) at presentation
2. Prior radiotherapy to the chest and/or other malignant diseases in the past
3. Concurrent chemotherapy

Recruitment start date

01/01/1999

Recruitment end date

31/05/2002

Locations

Countries of recruitment

Netherlands

Trial participating centre

Arnhems Radiotherapeutisch Instituut,
Arnhem
6815 AD
Netherlands

Sponsor information

Organisation

Arnhems Radiotherapeutic Institute (ARTI) (The Netherlands)

Sponsor details

Wagnerlaan 47
Arnhem
6815 AD
Netherlands

Sponsor type

Research organisation

Website

Funders

Funder type

Industry

Funder name

The Dutch Health Care Insurance Board (CVZ) (The Netherlands)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

Results in http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=ShowDetailView&TermToSearch=15860852

Publication citations

  1. Results

    Kramer GW, Wanders SL, Noordijk EM, Vonk EJ, van Houwelingen HC, van den Hout WB, Geskus RB, Scholten M, Leer JW, Results of the Dutch National study of the palliative effect of irradiation using two different treatment schemes for non-small-cell lung cancer., J. Clin. Oncol., 2005, 23, 13, 2962-2970, doi: 10.1200/JCO.2005.01.685.

Additional files

Editorial Notes