RENO

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:

Open Trial Recruitment Table

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