
- RENO
RENO is part of the AGITG Endorsed Study Model (please click here to find out more)
Trial Status
Open / Endorsed Studies
Cancer Type
Rectal Cancer
If you think this trial is relevant to your situation, please contact your Cancer Specialist to discuss further.
Protocol Title
Prospective Study of ‘Watch and Wait’ Strategy in Patients with Rectal Cancer who have Developed a Clinical Complete Response with concurrent Chemo‐radiotherapy: RENO trial (REctal cancer No Operation)
Purpose of the Study
Rectal cancer is a common malignancy and comprises a third of the cases of colorectal cancer.
Currently, combination of chemotherapy plus radiotherapy followed by surgical resection of the rectum is the standard management of locally advanced rectal cancer. Approximately 20% of patients develop a pathological complete response to chemoradiation. In these patients, surgery may not be necessary.
Eligibility Criteria
Inclusion Criteria
- Age 18 years or older
- Biopsy proven locally advanced rectal adenocarcinoma
- Subject to undergo Long Course Neoadjuvant Chemo-Radiotherapy based on a multidisciplinary meeting recommendation
- Considered suitable for long course pelvic radiation therapy
- Considered suitable for surgery
- Considered suitable for MRI
- Willing and able to comply with all study requirements, including treatment and follow up assessments
- Signed, written informed consent.
Exclusion Criteria
- Presence of metastatic disease (M1)
- T4 disease based on AJCC 2017
- Local recurrence of previously treated rectal cancer
- Previous pelvic radiotherapy
- Contraindication to fluoropyrimidine chemotherapy
- History of another malignancy
- Concurrent illness, including severe infection that may jeopardize the ability of the patient to undergo the chemoradiation with reasonable safety
- Presence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol including chemoradiation and/or follow-up schedule.
Contact Email
Study Chairs
Professor Chris Karapetis
Professor David Wattchow
Dr Sina Vatandoust
Dr Luigi Sposato
DETAILED INFORMATION AVAILABLE
Available online at the Australian New Zealand Clinical Trial Registry (ANZCTR) please click here.
Funding
2017 Innovation Fund Grant
Patients Recruited
Click here to access the table and view recruitment data on all AGITG open trials:
Participating Centres
Research Status
In Activation
Cancer Type
Rectal Cancer
If you think this research may be relevant to your patient or to discuss further, please contact the Research Team.
Protocol Title
Prospective Study of ‘Watch and Wait’ Strategy in Patients with Rectal Cancer who have Developed a Clinical Complete Response with concurrent Chemo‐radiotherapy: RENO trial (REctal cancer No Operation)
AIM
Primary Objectives:
The primary outcome measures will be studied in the Watch and Wait arm. These include the two‐year local recurrence rate and the associated rate of rectal preservation without local recurrence. A co‐primary endpoint is the two‐year local failure rate. Local recurrence that cannot be surgically resected with clear margins is defined as local failure. We aim to demonstrate that the local regrowth rate is not greater than 30%, indicating that at least 70% of patients can preserve rectal anatomy and avoid major surgery (rate of rectal preservation) without developing a local cancer recurrence. We also aim to demonstrate that the local failure rate (development of local cancer recurrence that cannot be resected) is less than 5% of the entire cCR cohort. The two‐year time frame will be calculated from the day of assignment to either ‘Watch & Wait’ or to ‘standard management’ i.e. surgery). Concurrent local recurrence and distant recurrence is considered local failure. Distant recurrence in the absence of local recurrence is not considered local failure. Survival analyses will represent secondary outcome measures. The 2‐year distant metastasis‐free survival and 2‐year survival will also be determined in the Watch & Wait arm.
Secondary Objectives:
The secondary outcome measures will be studied in both arms:
- To evaluate predictive blood and tumour biomarkers
- To evaluate diagnostic biomarkers and the application of a protocol mandated monitoring schedule, including MRI, CT, endoscopy and biopsy
- To investigate Patient Reported Outcome Measures, in both arms
- To determine the Cost Effectiveness of the ‘Watch and Wait’ strategy, an economic evaluation from a healthcare sector perspective will be conducted using a cost‐utility analysis, in which the effectiveness will be measured by Quality‐Adjusted Life‐Years (QALYs)
BACKGROUND
Rectal cancer is a common malignancy and comprises a third of the cases of colorectal cancer. In the majority of cases, the disease is localized at the time of diagnosis Currently, the combination of chemotherapy plus radiotherapy followed by surgical resection of the rectum is the standard management of locally advanced rectal cancer. Surgical resection of the rectum involves a mortality risk and can lead to considerable morbidity; in addition, many patients will need permanent stoma construction.2 Preoperative chemoradiotherapy (CRT) for rectal cancer can produce complete response. Surgery may not be necessary in these patients. Pathologic complete response (pCR) is achieved in up to 25% of patients with locally advanced rectal cancer after receiving CRT.3 Clinical complete response (cCR) may serve as a surrogate for pCR. In patients with cCR, no residual tumour is found on examination, imaging, endoscopy and biopsy. In patients with cCR, omission of surgery and a ‘Watch and Wait’ strategy that entails follow‐up and monitoring might be considered. This approach is known as non‐operative management or the ‘Watch and Wait’ strategy. These patients are monitored closely and if any sign of cancer recurrence is detected, the patient will proceed to have rectal surgery with curative intent. With this approach some patients will avoid unnecessary operations and the related mortality and morbidity risks.
RESEARCH DESIGN
This is a non‐randomised prospective cohort study. We have incorporated interim reviews and stopping rules to ensure safety. A consumer representative (cancer survivor) has provided input in designing the study. Potential participants will be consented prior to starting CRT. Blood and tumour samples for biomarker evaluation will be collected prior to CRT commencement from all patients. 8‐10 weeks after completing CRT, a colorectal surgeon will review the participants: based on the presence of any residual disease, participants will be allocated to one of the study arms:
- ‘Watch and Wait’ arm: Participants with no signs of residual disease (cCR) will be enrolled into the ‘Watch and Wait arm’ of the study. They will be carefully monitored for any sign of local recurrence during follow up reviews at defined intervals (which include clinical examination, endoscopy, biopsy and imaging assessments). Participants who develop any signs of recurrence will immediately be considered for surgery with curative intent.
- Standard Management arm: If any sign of residual cancer is found after completing CRT, the participant will be enrolled into the ‘standard management arm’ of the study and will proceed with standard management including surgery. They will be followed up as per a standard follow up schedule. In both arms, tissue and blood specimens and Patients Reported Outcome Measures will be collected.
Patients Recruited
Click to access the table and view recruitment data on all AGITG open trials:
Participating Centres
Key Eligibility Criteria
Inclusion Criteria:
Biopsy proven rectal adenocarcinoma, locally advanced disease [(T3 or resectable T4) and/or (node positive disease)], multidisciplinary meeting recommendation for long course CRT, adequate organ and bone marrow function.
Exclusion Criteria:
Presence of metastatic disease, pelvic sidewall infiltration, local recurrence of previous rectal cancer. Participants will be assessed after CRT. Participants with cCR will be allocated to the ‘Watch & Wait’ arm and participants with residual disease to the ‘Immediate Surgery’ arm.
Principal Investigator
Professor Chris Karapetis
More Information
Available online at the Australian New Zealand Clinical Trial Registry (ANZCTR) here.
Funding
2017 Innovation Fund Grant