None listed
Conditions
Brief summary
Lung cancer is the fifth most common cancer in Australia and the leading cause of cancer deaths. The majority of lung cancers are of the Non Small Cell Lung Cancer (NSCLC) histological type and most patients present with inoperable Stage III or IV disease. The population to be studied in this trial are patients with inoperable NSCLC who have a good PS but locally advanced or limited metastatic disease for whom radical CT-RT (=60Gy) is not feasible either due to tumour extent or patient factors. In these patients, the aim of therapy is to achieve symptom control and maintain Quality of Life (QOL). However, the optimal treatment regimen for this group is uncertain. Hypothesis- The hypothesis is that the addition of chemotherapy to high dose palliative radiotherapy in these patients will maximises intrathoracic symptom palliation (both the extent of improvement and its duration), which will lead to an improvement in QOL, and is associated with acceptable toxicity, compared with high dose palliative radiotherapy alone. Objectives- The Primary objective is to compare, in this group of patients, high dose palliative radiotherapy (HDPRT) versus concurrent chemotherapy and HDPRT (C-HDPRT), with respect to - The relief of dyspnoea, cough, haemoptysis and chest pain as assessed by change in total symptom burden from baseline to six weeks after the completion of treatment. - Response for each component symptom separately (dyspnoea, cough, haemoptysis, chest pain) The secondary objectives are to compare the two regimens in terms of; Dysphagia during treatment, Thoracic symptom response rate, Duration of thoracic symptom response , QOL, Toxicity, Progression-free survival and Overall survival. The exploratory/tertiary objectives are; - to determine how much improvement in QoL and symptom palliation would be necessary to make the inconvenience due to the longer duration of radiotherapy of C-HDPRT worthwhile, relative to HDPRT. This objective will be addressed in the Patient Preferences Substudy. - Analyse serum protein glycosylation changes and exosomes to identify potential biomarkers of disease response and progression - Prospectively collect and bank tumour tissue and blood samples from this cohort of patients for future evaluation of potential biological markers End Points- Primary - - Change from baseline at 6 weeks after treatment in the Intrathoracic Symptom Burden Index - Change from baseline at 6 weeks after treatment in each of the component symptoms, dyspnoea, cough, haemoptysis and chest pain. Secondary - - Profile of change from baseline of Intrathoracic Symptom Burden Index, and of component symptoms, by time (6 weeks, 3, 6, 12, 24 months) - Thoracic symptom response rate and response duration - Physician’s rating of cough, dyspnoea, haemoptysis and chest pain, summed into a symptom index and performance status (Karnofsky) and QOL (Spitzer) - Toxicity measured by NCIC CAE v 3.0 - Tumour response, Progression-free survival and Overall survival Trial Design- This is a multi-centre, two-arm, randomised (1:1) Phase III trial to compare high dose palliative radiotherapy (HDPRT) versus concurrent chemotherapy and HDPRT (C-HDPRT) in patients with inoperable NSCLC. 1) ARM A (control arm): High dose palliative RT (HDPRT) alone (36Gy/12 fractions, 4-5 fractions/week) or 2) ARM B (investigational arm): Chemotherapy + HDPRT (40Gy/20fractions, 4-5 fractions/week + IV cisplatin 20mg/m2 days 1, 8, 15, 22 + IV vinorelbine 25mg/m2 days1, 8, 22). (C + HDPRT) All eligible patients will be stratified according to tumour stage, histology, major chest symptoms and treating institution. The total participant accrual for this trial will be 130. The accrual period is expected to be 41 months and total study duration 55 months.
Interventions
Chemotherapy + High Dose palliative Radiation Therapy (C-HDPRT)
1. Radiation Therapy; 40Gy/20f (2Gy/f, 4-5f/week)
2. Chemotherapy; IV cisplatin 20mg/m2 (days 1, 8, 15, 22 of RT) plus IV vinorelbine 25mg/m2 (days 1, 8 and 22 of RT).
Sponsors
Trans Tasman Radiation Oncology Group
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
18 Years to 100 Years
Healthy volunteers
No
Inclusion criteria
1. Aged 18 years or older 2. ECOG PS 0-1, 3. Histological or cytological proven stage III or IV NSCLC of any subtype: Adenocarcinoma, Squamous Cell Carcinoma (SCC), NSCLC Not Otherwise Specified (NOS) or Other (including Large Cell Undifferentiated). 4. Symptoms due to intrathoracic disease (at least one of cough, dyspnoea, haemoptysis, chest pain), 5. Patients with Stage III NSCLC not suitable for radical chemo-radiotherapy (due to concurrent medical illness, weight loss > 10% or tumour volume too large for radical radiation fields (e.g. dose constraints for organs at risk cannot be met using radical radiation fields or at the discretion of the investigator) or patients with locally advanced thoracic disease and a FDG-PET detected solitary metastasis (small volume Stage IV disease), Not cerebral metastasis 6. Planned for HDPRT to achieve local control 7. Adequate organ function; a) Bone marrow: Haemoglobin (Hb) >/= 100g/l, Absolute neutrophil count (ANC) >/= 1.5 , Platelet count >/= 100 b) Hepatic: Serum bilirubin </= 1.0 x upper limit of normal (ULN), AST/ALT </= 2.0 x ULN, ALP </= 2.5 x ULN. c) Renal: Creatinine Clearance >/= 55 ml/min 8. No prior therapy for NSCLC 9. Able to commence Radiotherapy no later than 6 weeks, but preferably within 4 weeks from the time of participant randomisation. It is preferred that RT be commenced on a Monday or Tuesday. 10. Has provided written informed consent to participate in this trial 11. Participants capable of childbearing are using adequate contraception 12. Available for follow-up for a minimum of 3 months.
Exclusion criteria
1. Receiving treatment with another investigational agent 2. History of any other cancer (except non-melanomatous skin cancer or carcinoma in situ of the cervix) unless in complete remission and off all therapy for that cancer for at least 3 years. 3. Women who are pregnant or lactating 4. Previous radiotherapy to the area to be treated, at any time. 5. Significant medical conditions which in the opinion of the investigator would compromise the planned delivery of the chemotherapy and radiotherapy or which may be potentially exacerbated by these modalities
Outcome results
None listed