Clinical trial NCT00193882: Advanced Oesophageal Cancer Study to Compare Quality of Life and Palliation of Dysphagia.
Official title: A Randomised Phase III Study in Advanced Oesophageal Cancer to Compare Quality of Life and Palliation of Dysphagia in Patients Treated With Radiotherapy vs ChemoRadiotherapy.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Esophagus Cancer
Keywords: Oesophageal
Dysphagia
Palliation
Quality of Life
Radiotherapy
Chemotherapy
Lead sponsor: Trans Tasman Radiation Oncology Group
Sponsor class: OTHER
Collaborators: name: National Health and Medical Research Council, Australia
name: Canadian Cancer Trials Group
First posted: 2005-09-19
Enrollment: 220
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: To compare the treatment of gullet cancer with radiotherapy alone and assess the advantage and toxicity of adding chemotherapy. The hypothesis to be tested is as follows: That the addition of chemotherapy to a short course of radiation treatment improves the proportion of patients who achieve relief of dysphagia and improves quality of life compared to radiation alone in patients with advanced oesophageal cancer.

Detailed description: Prospective radical treatment trials in oesophageal cancer have shown responses in both radiotherapy alone and radiotherapy when combined with chemotherapy. Retrospective studies show a response in the palliative setting to relieve dysphagia. The response, durability and quality of life end points have not been previously fully documented. This will be addressed by this trial.

Dysphagia is the commonest presenting symptom due to local disease obstructing the oesophagus. Difficulty eating not only affects the patient's ability to maintain nutrition, but also impacts on all areas of quality of life. Relief of dysphagia becomes the highest priority for treatment.

At the time of developing this protocol there were no randomised trials comparing chemo-radiotherapy and radiotherapy in the palliative setting.

Few studies have prospectively assessed quality of life data for patients with oesophageal cancer, and although toxicity and survival data is available, there is no long-term data on quality of life. This trial will assess quality of life in a consecutive manner using a standardised self-reporting measure of quality of life, and compare quality of life across two groups having different treatments.

Eligible patients are those with proven carcinoma of the oesophagus who are deemed not suitable for definitive radical treatment due to the advanced nature of disease, presence of metastases or intercurrent illness, who have symptomatic dysphagia requiring loco-regional palliation.

Patients will be randomised to the following treatment options:

1. Radiotherapy Alone

   * 35 Gy in 15 fractions (Australia and New Zealand) or
   * 30 Gy in 10 fractions(Canada ONLY)
2. Chemo-Radiotherapy

   * 35 Gy in 15 fractions (Australia and New Zealand) or
   * 30 Gy in 10 fractions (Canada ONLY)
   * Cisplatin 80mg/m2 IV day 1 (or 20mg/m2/day IV days 1 - 4)
   * 5-Fluorouracil 800mg/m2/day IV days 1 - 4

Patients will have an initial baseline assessment then be followed up weekly during treatment, monthly for 1 year post treatment and then 3 monthly.

Eligibility criteria: Inclusion Criteria:

* Biopsy proven Carcinoma of the oesophagus.
* Not a candidate for radical/curative treatment due to the advanced nature of the disease, presence of metastases, or intercurrent illness. (It should be noted that, patients with mediastinal nodes and no more distant disease maybe suitable for radical treatment).
* Symptomatic patients with dysphagia scores of ≥ 1 i.e. able to eat only some solids (see Mellow Scale appendix 1)
* Performance status ECOG ≤ 2
* Patients must begin treatment within 2 weeks of randomization.
* Patient is at least 18 years old.
* Adequate haematological function to undergo chemotherapy. Peripheral blood - Neutrophils \> 1.5 x 10\^9/L - Platelets \> 100 x 10\^9/L
* Adequate renal function, Creatinine - Calculated clearance ≥ 50 ml/min
* Patients capable of childbearing are using adequate contraception.
* Written informed consent of patient.

Exclusion Criteria:

* Previous mega-voltage external beam Radiotherapy or brachy-therapy delivered to the region of the chest.
* Synchronous active malignancies.
* Pregnant or lactating patients.
* Patients unfit for any treatment component.
* Tracheo-oesophageal fistula.
* Stents in situ.
* Previous chemotherapy for Oesophageal Cancer
* CT scan of thorax and abdomen more than 8 weeks prior to randomization
* Full Blood Count, Biochemistry (including creatinine) and creatinine clearance more than 2 weeks prior to randomization

Primary outcomes:
measure: Relief of dysphagia
timeFrame: This will be measured at nine weeks after the start of radiotherapy and must be maintained at the next review 4 weeks thereafter.
Secondary outcomes:
measure: Dysphagia progression free survival.
timeFrame: This will be measured from randomisation to the time of first progression of dysphagia.
measure: Quality of Life differences post treatment and at 3 months and 6 months.
timeFrame: post treatment and at 3 months and 6 months.
measure: Acute and late toxicity.
timeFrame: Interim analyses planned at 110 pateints. Final analyses will occur after 5 years.
measure: Survival.
timeFrame: Interim analyses planned at 110 pateints. Final analyses will occur after 5 years.
measure: Time to achieving any response in dysphagia after treatment as measured by an improvement of at least 1 point on the 5 point dysphagia scale.
timeFrame: Interim analyses planned at 110 pateints. Final analyses will occur after 5 years.
measure: Number of patients receiving secondary treatment (radiation, chemotherapy or stenting).
timeFrame: Interim analyses planned at 110 pateints. Final analyses will occur after 5 years.
measure: Time to achieving a complete response i.e. dysphagia score of 0.
timeFrame: Interim analyses planned at 110 pateints. Final analyses will occur after 5 years.
Other outcomes:
Locations:
city: Liverpool
country: Australia
facility: Liverpool Hospital
state: New South Wales
city: Randwick
country: Australia
facility: Prince of Wales Hospital
state: New South Wales
city: Sydney
country: Australia
facility: Royal North Shore Hospital
state: New South Wales
city: Auchenflower
country: Australia
facility: Premion - Wesley
state: Queensland
city: Herston
country: Australia
facility: Royal Brisbane Hospital
state: Queensland
city: South Brisbane
country: Australia
facility: Radiation Oncology - Mater Centre
state: Queensland
city: Townsville
country: Australia
facility: North Queensland Oncology Service
state: Queensland
city: Woolloongabba
country: Australia
facility: Princess Alexandra Hospital
state: Queensland
city: Adelaide
country: Australia
facility: Royal Adelaide Hospital
state: South Australia
city: Launceston
country: Australia
facility: Launceston General Hospital
state: Tasmania
city: Box Hill
country: Australia
facility: Peter MacCallum - Box Hill Hospital
state: Victoria
city: east Bentleigh
country: Australia
facility: Peter MacCallum - Moorrabbin
state: Victoria
city: Geelong
country: Australia
facility: Andrew Love Cancer Care Centre, Geelong Hospital
state: Victoria
city: Melbourne
country: Australia
facility: Peter MacCallum Cancer Centre
state: Victoria
city: Perth
country: Australia
facility: Royal Perth Hospital
state: Western Australia
city: Edmonton
country: Canada
facility: Cross Cancer Centre
state: Alberta
city: Winnipeg
country: Canada
facility: Cancer Care Manitoba Winnipeg
state: Manitoba
city: Saint John
country: Canada
facility: Saint John Regional Hospital - Atlantic Health Sci
state: New Brunswick
city: Halifax
country: Canada
facility: Nova Scotia Cancer Centre
state: Nova Scotia
city: Kingston
country: Canada
facility: Cancer Centre of Southeastern Ontario Kingston
state: Ontario
city: Kitchener
country: Canada
facility: Grand River Cancer Centre
state: Ontario
city: Toronto
country: Canada
facility: Princess Margaret Hospital
state: Ontario
city: Quebec
country: Canada
facility: Hotel-Dieu de Quebec
city: Christchurch
country: New Zealand
facility: Christchurch Hospital
city: Hull
country: United Kingdom
facility: Princess Royal Hospital
Study officials:
affiliation: Royal Adelaide Hopsital
name: Michael Penniment, FRANZCR
role: STUDY_CHAIR
References:
citation: Penniment MG, De Ieso PB, Harvey JA, Stephens S, Au HJ, O'Callaghan CJ, Kneebone A, Ngan SY, Ward IG, Roy R, Smith JG, Nijjar T, Biagi JJ, Mulroy LA, Wong R; TROG 03.01/CCTG ES.2 group. Palliative chemoradiotherapy versus radiotherapy alone for dysphagia in advanced oesophageal cancer: a multicentre randomised controlled trial (TROG 03.01). Lancet Gastroenterol Hepatol. 2018 Feb;3(2):114-124. doi: 10.1016/S2468-1253(17)30363-1. Epub 2017 Dec 14.