Advanced Oesophageal Cancer Study to Compare Quality of Life and Palliation of Dysphagia.

Trans Tasman Radiation Oncology Group

Status and phase: Completed; Phase 3

Conditions: Esophagus Cancer

Treatments: Drug: 5-Fluorouracil; Radiation: Radiotherapy; Drug: Cisplatin

Study type: Interventional

Funder types: Other; NETWORK

Identifiers

NCT00193882

NHMRC 291103 (Other Identifier)

NCIC CTG ES.2 (Other Identifier)

TGA 2004/83 (Other Identifier)

TROG 03.01

Details and patient eligibility

About

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.

Full 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.

Enrollment: 220 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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220 participants in 2 patient groups

A: Radiotherapy

Active Comparator group

Description:

Radiotherapy alone

Treatment:

Radiation: Radiotherapy

B: Chemo-radiotherapy

Experimental group

Description:

Chemotherapy (Cisplatin + 5-Fluorouracil ) and Radiotherapy

Treatment:

Drug: Cisplatin

Radiation: Radiotherapy

Drug: 5-Fluorouracil