Condition category
Cancer
Date applied
18/01/2008
Date assigned
13/02/2008
Last edited
13/02/2008
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 Torsten Liersch

ORCID ID

Contact details

Georg-August University of Gottingen
Department of General and Visceral Surgery
Robert-Koch-Strasse 40
Göttingen
37075
Germany
+49 (0)5513 983 23
tliersc@gwdg.de

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

N/A

Study information

Scientific title

Therapy of cUICC stage II/III rectal cancer of the upper third by quality controlled total versus partial mesorectal excision, followed by adjuvant chemotherapy

Acronym

GAST-05

Study hypothesis

The multicentric GAST-05 study aims at identifying the optimal surgical treatment of locally advanced (cUICC stage II/III) rectal cancer located 12 - 16 cm above the anocutaneous verge. Two established surgical techniques are compared:
1. Total mesorectal excision (TME), to completely eliminate affected and surrounding tissue, bears the risk of post-surgical complications
2. Partial mesorectal excision (PME) restricts surgery to the afflicted tissue and defined surroundings

PME may be equally effective in eliminating cancer while limiting post-operative complications. No clinical data have been raised to date that show if TME or PME is oncologically superior. To answer this requires a refocus on the principles of both resection techniques, including peri- and post-operative quality control. Post-surgical chemotherapy is identical in both trial arms. Primary endpoint is the disease-free survival after 3 years.

The GAST-05 study is an add-on study to the ongoing CAO/AIO/ARO-04 trial, which intends to optimise the pre-surgical chemoradiotherapy of cUICC stage II/III cancers in the lower two thirds of the rectum (0 - 12 cm). The comparison of the long-term outcomes of both studies (GAST-05: surgical procecures; CAO/AIO/ARO-04: intensified preoperative treatment) will influence future studies; they will apply the surgical procedure that is identified as being superior during the GAST-05 study. Additional gene expression analyses on pre-therapeutically taken tumour probes will show if gene profiling can help to predict individual prognosis.

The identification of the oncologically superior of two standardised surgical treatments (TME and PME) of cUICC stage II/III cancers of the upper third of the rectum has not been determined. The identification is a prerequisite for further studies, needed to reduce the side effects of optimised surgical treatments. If both techniques, TME and PME, turn out to be equivalent, that technique will be regarded as superior, which promises less comorbidities, a higher qualitiy of life, and lower health care costs (i.e. PME).

A cross-comparison of disease-free and overall survival data from the GAST-05 trial and the CAO/ARO/AIO-04 trial will further allow judgement on the need for further studies on multimodal therapies for rectal cancers of the upper third. If the rate of local and distant metastases turns out to be equal or lower in the GAST-05 trial (upper third, no neoadjuvant RT/CT, PME/TME) than in the CAO/ARO/AIO-04-trial (lower two thirds, intensified preoperative treatment), further trials may be unnecessary which test multimodal therapies in cancers of the upper third. Patients with cUICC stage II/III cancers of the upper third of the rectum will then be spared potentially ineffective preoperative radiochemotherapy with its toxicities.

Ethics approval

Ethics approval received from the Georg-August-University Gottingen Ethik-Kommission der Medizinischen Fakultat on the 17th January 2007 (ref: 21/11/06).

Study design

Open, multi-centric, prospectively randomised phase II trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet.

Condition

Rectal cancer

Intervention

For all procedures, standard operating procedures (SOPs) are available.

Experimental intervention:
1. Arm A: total mesorectal excision (TME) including surgical and pathological quality control, followed by standard adjuvant chemotherapy. The mesorectum is completely excised downwards to the pelvic floor:
1.1. Dorsally: entire retro-rectal fat body with the lymph tissue under consideration of the fascial system
1.2. Ventrally: including the spatium prerectale along the Denonvilliers-fascia
1.3. Laterally: entire area up to pelvis

2. Arm B: Partial mesorectal excision (PME) including surgical and pathological quality control, followed by adjuvant chemotherapy. PME follows the same surgical principles as in TME with the following exception: the mesorectum is transected at a right angle to the rectal wall 5 cm beyond the gross distal margin of the tumour, as measured in situ

In both trial arms, surgery is followed by adjuvant chemotherapy:
1. Folinic acid: 400 mg/m^2, 2-hour infusion, day 1
2. Oxaliplatin: 100 mg/m^2 2-hour infusion in 500 ml glucose 5%, day 1
3. 5-Fluorouracil: 2400 mg/m^2 as 46-hour infusion

Perioperative assessment of mesorectal excision (TME/PME):
Staining of the specimen via inferior mesenteric artery, photo-documentation:
Class 1: no leakage, optimal TME/PME
Class 2: punctual leakage(s), good TME/PME
Class 3: extensive leakage(s), incomplete TME/PME

Standardised pathological assessment of TME/PME (in addition to established TNM/UICC criteria):
Extent: TME/PME?
In case of PME:
1. Distance between macroscopically visible distal margin of tumour and distal transection margin measured in centimetres. Measuring method:
1.1. Fresh, non-stretched specimen
1.2. After fixation (non-pinned)
1.3. After fixation (pinned, non-stretched)
2. Coning (distal transaction in a plane at 90° to the rectal wall): no, yes
3. Macroscopic assessment of the specimen surface in all cases:
3.1. Intact, smooth (lipoma-like)
3.2. Circumscribed defect(s) no greater than 5 mm
3.3. Extensive defect(s), muscular layer of the rectum invisible
3.4. Extensive defect(s), muscular layer of the rectum visible
3.5. Incision into the tumour or tumour torn open

Pathological quality assessment of the specimens after TME/PME:
1. Complete: intact mesorectum, no defects larger than 5 mm, no PME-coning, smooth circumferential resection margin on slicing
2. Moderate: irregular mesorectal surface, moderate PME-coning, muscularis propria invisible with the exception of area of insertion of levator muscles, moderate irregularity of the circumferential resection margin
3. Incomplete: little bulk of mesorectum with defects down into mucularis and/or very irregular circumferential resection margin, PME-coning

Control intervention:
None

Duration of intervention per patient: 32 weeks
Follow-up per patient: 3 years

Intervention type

Drug

Phase

Phase II

Drug names

Folinic acid, oxaliplatin, 5-Fluorouracil

Primary outcome measures

Disease-free survival after 3 years (local and/ or distant recurrences).

Secondary outcome measures

1. R0-rate of resection
2. Post-operative 30-day lethality
3. Post-operative morbidity (especially rate of anastomotic insufficiencies)
4. Cumulative incidence of local relapses and distant metastases
5. Survival after 3 and 5 years
6. Acute and late toxicity of the chemotherapy according to the Common Toxicity Criteria of the National Cancer Institute (NCI CTC version 2.0)
7. Post-operative late complications (defaecation problems, anastomotic stenoses, loss of sphincter function)
8. Quality of TME and PME as assessed
9. Quality of life according to the European Organisation for Research and Treatment of Cancer (EORTC)-Questionnaire QLQ-30 (3.0)

Assessment of safety: TME, PME, and adjuvant chemotherapy are established procedures.

Overall trial start date

01/10/2007

Overall trial end date

30/06/2013

Reason abandoned

Eligibility

Participant inclusion criteria

1. Histologically confirmed advanced primary rectum carcinoma at a level 12 - 16 cm above the anocutaneous verge (as measured by rigid endoscopy), endosonographically classified as uT3-4 or uN+ carcinomas, no evidence for synchronous distant metastases
2. Patients aged 18 - 85 years, either sex
3. No preliminary treatment of rectum carcinoma

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

360

Participant exclusion criteria

1. Successfully treated secondary malignoma with the exception of basal cell carcinoma of the skin and in situ cervix carcinoma, respectively, The inclusion of patients with other tumours, that have been treated successfully and have not reappeared during the last 5 years, has to be discussed with the principal investigator
2. Simultaneous therapy with other anti-cancer drugs
3. Chronic colonic diseases

Recruitment start date

01/10/2007

Recruitment end date

30/06/2013

Locations

Countries of recruitment

Germany

Trial participating centre

Georg-August University of Gottingen
Göttingen
37075
Germany

Sponsor information

Organisation

Georg-August University of Gottingen (Georg-August-Universitat Gottingen, Universitatsmedizin) (Germany)

Sponsor details

c/o Prof. Dr. med. H. Becker and Dr. med. Torsten Liersch
Department of General and Visceral Surgery
Robert-Koch-Strasse 40
Göttingen
37075
Germany
+49 (0)5513 983 23
tliersc@gwdg.de

Sponsor type

University/education

Website

http://www.uni-goettingen.de/en/sh/1.html

Funders

Funder type

Government

Funder name

German Research Council (Deutsche Forschungsgemeinschaft [DFG]) (Germany) (ref: 518)

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

Publication citations

Additional files

Editorial Notes