A Randomised Phase II Trial of Pre-operative cisplatin, 5 fluorouracil and docetaxel ± Radiotherapy based on poor early response to standard chemotherapy for resectable adenocarcinoma of the oesophagus and/or OG Junction.

• Register: ANZCTR
• Last refreshed on: 13 January 2020
• Main ID: ACTRN12609000665235
• Date of registration: 05/08/2009
• Prospective Registration: No
• Primary sponsor: AGITG
• Public title: A Randomised Phase II Trial of Pre-operative cisplatin, 5 fluorouracil and docetaxel ± Radiotherapy based on poor early response to standard chemotherapy for resectable adenocarcinoma of the oesophagus and/or OG Junction.
• Scientific title: A Randomised Phase II Trial of Pre-operative cisplatin, 5 fluorouracil and docetaxel +/- Radiotherapy based on poor early response to standard chemotherapy for resectable adenocarcinoma of the oesophagus and/or Oesphago-gastric Junction.
• Date of first enrolment: 01/07/2009
• Target sample size: 150
• Recruitment status: Completed
• URL: https://anzctr.org.au/ACTRN12609000665235.aspx
• Study type: Interventional
• Study design: Purpose: Treatment; Allocation: Randomised controlled trial; Masking: Open (masking not used);Assignment: Parallel;Type of endpoint: Safety;
• Phase: Phase 2

Countries of recruitment

Australia

Contacts

• Name: A/Prof Andrew Barbour c/- DOCTOR Trial Coordinator

• Name: Ms DOCTOR Trial Coordinator

Key inclusion & exclusion criteria

Inclusion criteria: 1. Histologically proven invasive adenocarcinoma of the oesophagus or gastroesophageal junction.

2. Tumour thought to be T2 or greater or T1 tumours that are poorly differentiated or thought to be node-positive.

3. Technically resectable disease, as assessed in consultation with the intended surgeon.

4. Tumour is sufficiently F-18 fluorodeoxyglucose (FGD) avid on the initial staging PET scan to provide sufficient contrast between tumour and the surrounding normal tissues so that a response to the neoadjuvant therapy may be assessed.

5. Written informed consent of the patient according to local ethics committee guidelines.

6. Medically fit for surgical resection, defined as having adequate cardiopulmonary function and Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
Exclusion criteria: 1. Evidence of extrathoracic or extragastric spread apart from perigastric or mediastinal nodes, which are resectable. (Supraclavicular nodes renders the patient ineligible) 2. Tumour is located in the cervical oesophagus requiring pharyngolaryngectomy. 3. Tumour is predominantly within the stomach ie. most of the tumour is not involving the oesophagus or gastroesophageal junction. 4. Evidence of tracheo- or broncho oesophageal fistula. 5. Adequate haematological function. 6. Adequate renal function 7. Adequate liver function 8. Previous radiation therapy to the chest, previous chemotherapy within the last 5 years. 9. Previous malignancy for the previous 5 years apart from non metastatic Squamous Cell Carcinoma of the skin, Basal Cell Carcinoma or carcinoma in situ of the cervix. 10. Pregnant, lactating or inadequate contraception.

Age minimum: 18 Years
Age maximum: No limit
Gender: Both males and females

Health Condition(s) or Problem(s) studied

Cancer - Oesophageal (gullet)

Adenocarcinoma of the Oesophagus and/or OG Junction;
Adenocarcinoma of the Oesophagus and/or OG Junction

Intervention(s)

Randomised study of patients that have not shown early response to standard chemotherapy. All participants receive the standard treatment of a 21 day cycle of Cisplatin 80mg/m2 (intravenously infused over 2 hours) Day 1 and 5-Fluorouracil 1000 mg/m2 (continuous infusion) Days 1-4. All participants are restaged at day 15 with Positron Emission Tomography (PET). If significant response then standard treatment is repeated over another 21 day cycle. However if no significant response, subjects will be randomised to receive either 2 x 21 day cycles of Cisplatin 60mg/m2 (intravenously infused over 2 hours) on day 22 & day 50, Docetaxel 35mg/m2 (intravenously infused over 1 hour) on Day 22, 29, 36, 50 ,57 & 64 & 5-Fluorouracil 150mg/m2 continuous intravenous infusion for 6 weeks starting Day 22 OR Cisplatin 60mg/m2 (intravenously infused over 2 hours) on day 22 & day 50, Docetaxel 35mg/m2 (intravenously infused over 1 hour) on Day 22, 29, 36, 50 ,57 & 64 & 5-Fluorouracil 150mg/m2 continuous intravenous infusion for 6 weeks starting Day 22 plus radiation 45Gy/25Fr starting Day 22. Radiation will be administered once daily, Monday to Friday on 25 occasions. All participants will have surgery in an attempt for complete resection, 4 - 8 weeks after completion of neoadjuvant therapy. The operation should aim to remove the tumour in total, with an adequate margin in each direction. This may be done as a subtotal esophagectomy with proximal gastric resection and a right intrathoracic oesophago-gastrostomy (Ivor–Lewis procedure), a subtotal oesophagectomy with proximal gastric resection and a cervical oesophago-gastrostomy (McKeon procedure). This is a complicated surgery often taking more than 6 hours.

Primary Outcome(s)

To evaluate the histological response to the neoadjuvant therapy regime[Tumour samples will be taken at baseline and at surgery (after neoadjuvant therapy). After 23 patients have completed neoadujvant treatment and no histological responses have been observed then consideration will be given to stopping that particular arm.]

Secondary Outcome(s)

To evaluate the toxicity of Docetaxel in combination therapy for oesophageal cancer. This will be done be review of clinical data such as physical exams and blood analysis.[Toxicity will be assessed weekly whilst participants are receiving docetaxel. Toxicity will be assessed pre-surgery, 6 weeks post surgery, 12 weeks post surgery, every 3 months for 2 years, then every 6 months out to 5 yrs]

To evaluate the early PET response to the induction neoadjuvant therapy regimen[Pet scans will be done at baseline and then day 15.]

To evaluate the overall survival in the three treatment arms[After follow up completed for enrolled patients. Patients will followed up until 5 years post surgery.]

To assess the effect of the treatment regimen on quality of life in each of the treatment arms. To be assessed by quality of life forms.[Quality of life forms done at baseline, pre-surgery and at various timepoints though-out the 5 year follow up period. Surgery will be done 4-8 weeeks after completion of neoadjuvant therapy. To ensure participants have recovered.]

To evaluate the disease-free survival in the three treatment arms.[After follow up completed for enrolled patients. Patients will followed up until 5 years post surgery.]

To evaluate the tumour down-staging in the three treatment arms.

Participants will be restaged post completion of neoadjuvant therapy with endoscopy, computed tomography scan and comparison of pre and post neoadjuvant tumour samples[Studies to be done on tissue samples banked at baseline and pre-surgery. Surgery will be done 4-8 weeeks after completion of neoadjuvant therapy. To ensure participants have recovered.]

Secondary ID(s)

NIL

Source(s) of Monetary Support

NHMRC

Ethics review

Status: Approved
Approval date:
Contact:

Cancer Institute NSW

Status: Approved
Approval date:
Contact:

Greenslopes Private Hospital

Status: Approved
Approval date:
Contact:

Princess Alexandra Hospital

Status: Approved
Approval date:
Contact:

SLHD Ethics Review Committee (RPAH Zone)