Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12619000207112
Ethics application status
Approved
Date submitted
23/01/2019
Date registered
13/02/2019
Date last updated
29/10/2024
Date data sharing statement initially provided
13/02/2019
Type of registration
Retrospectively registered

Titles & IDs
Public title
A Longitudinal Cohort Study of ‘Watch and Wait’ in Complete Clinical Responders after Chemo-radiotherapy for Localised Rectal Cancer
Scientific title
A Longitudinal Cohort Study of ‘Watch and Wait’ in Complete Clinical Responders after Chemo-radiotherapy for Localised Rectal Cancer
Secondary ID [1] 297185 0
Nil known
Universal Trial Number (UTN)
Trial acronym
REctal cancer Non-Operative (RENO)
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Rectal Cancer 311238 0
Condition category
Condition code
Cancer 309860 309860 0 0
Bowel - Back passage (rectum) or large bowel (colon)

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Patients will complete chemoradiation and then based on response (complete response or other) they will be allocated to one of the two study cohorts; follow up with MRI scans (complete responders -considered the intervention arm) or surgery (other).
The surgery is considered the standard arm.
For patients whom are complete responders and go onto the MRI arm, they will not receive surgery. Instead they will be followed up with clinical assessments and sigmoidoscopy, 3-monthly for the first two years, then 6-monthly in years 3-5; CT scans at 6, 12, 24, 36, 48 and 60 months; MRI and blood tests every 3 months in the first year then 6-monthly in years 2-5.
Intervention code [1] 313444 0
Treatment: Other
Comparator / control treatment
Patients will complete chemoradiation and then based on response (complete response or other) they will be allocated to one of the two study cohorts; follow up with MRI scans (complete responders) or surgery (other). Surgery is the control and the standard pathway for patients. [Clinical practice guidelines for the prevention, early detection and management of colorectal cancer” developed by Cancer Council Australia,
These guidelines are in line with the available evidence and in keeping with recommendations from international guidelines (ESMO and NCCN)]
Control group
Active

Outcomes
Primary outcome [1] 318804 0
Determine the efficacy of the ‘Watch and Wait’ strategy, by measuring the following endpoints: a. Co-Primary endpoint-1: The ‘three-year local failure rate’ (in the ‘Watch and Wait’ arm) defined as local recurrence that cannot be resected with clear margins - determined by patients through MRI, CT scan and surgical review.
Timepoint [1] 318804 0
This will be assessed at three years after commencing therapy using the Sigmoidoscopy, CT scan and MRI & blood tests.
Primary outcome [2] 318969 0
b. Co-Primary endpoint-2: The rate of rectal preservation (in the ‘Watch and Wait’ arm) measured by number of patients not requiring surgery
Timepoint [2] 318969 0
Three years after commencing therapy.
Secondary outcome [1] 366102 0
1. Determine the safety of the ‘Watch & Wait’ strategy by measuring the following endpoint (in the watch and wait arm): (composite) a. The ‘three-year local recurrence rate’ b. The ‘three-year distant metastasis rate’ c. The overall survival d. The ‘incurable disease-free survival rate’ (recurrent cancer that cannot be surgically excised with the intention of achieving a cure) .These will be assessed through the use of MRI's, CT scans, sigmoidoscopy and clinical examinations.
Timepoint [1] 366102 0
This will be assessed at three years following commencing chemoradiation using the following: Sigmoidoscopy, 3-monthly for two years then 6-monthly, CT scan 6-monthly for a year then 12-monthly, MRI & blood tests 3-monthly for a year then 6 monthly, Clinic visit 3-monthly for 2 years then 6-monthly.
Secondary outcome [2] 366104 0
To investigate Patient reported Outcome Measures -Quality of Life

Quality of Life is defined as the general well-being of the individual; this outcome is measured using the EORTC QLQ-C30 questionnaire which is a validated questionnaire developed to assess the quality of life of cancer patients. The EORTC QLQ-CR-29 will also be used; this is a validated questionnaire developed to assess the quality of life of patients with a history of colorectal cancer and is used in addition to the EORTC QLQ-C30 questionnaire.
Timepoint [2] 366104 0
Completed by all patients at screening, at 8-10 weeks post chemoradiotherapy (or 18-20 weeks post chemoradiotherapy if receiving Total Neoadjuvant Therapy), then yearly for 5years post chemoradiotherapy.
Secondary outcome [3] 366873 0
To investigate Patient reported Outcome Measures - Health Related Quality of Life.

Health-related quality of life is a multi-dimensional concept that includes domains related to physical, mental, emotional and social functioning. This outcome will be measured using a validated questionnaire: the EQ-5D-5L questionnaire
Timepoint [3] 366873 0
Completed by all patients at screening, at 8-10 weeks post chemoradiotherapy (or 18-20 weeks post chemoradiotherapy if receiving Total Neoadjuvant Therapy), then yearly for 5years post chemoradiotherapy.
Secondary outcome [4] 366874 0
To investigate Patient reported Outcome Measures - Fear of Cancer Recurrence

Fear of Cancer Recurrence (FCR) defined as feeling anxious about the cancer coming back and is measured by Fear of Cancer Recurrence Inventory (FCRI SF). To interpret the FCR results and to measure response efficacy we will use a modified Response Efficacy Scale specifically designed for this study.
Timepoint [4] 366874 0
Patients will complete the Fear of Cancer Recurrence Inventory and The Response efficacy questionnaire yearly for 5years post chemoradiotherapy.
Secondary outcome [5] 366875 0
To investigate Patient reported Outcome Measures - survivorship and supportive care needs

Ongoing supportive care needs across the survivorship continuum will be measured using Cancer Survivors unmet needs (CaSUN) questionnaire
Timepoint [5] 366875 0
Completed by patients at screening, at 8-10 weeks post chemoradiotherapy (or 18-20 weeks post chemoradiotherapy if receiving Total Neoadjuvant Therapy), then yearly for 5years post chemoradiotherapy.
Secondary outcome [6] 366876 0
To investigate Patient reported Outcome Measures - Bowel Related Quality of Life.

This outcome encompasses multiple aspects of bowel function and will be measured using the MSKCC Bowel Function Questionnaire and LARS score.
Timepoint [6] 366876 0
All patients will complete the MSKCC and LARS questionnaires at screening and at 8-10 weeks post chemoradiotherapy (or 18-20 weeks post chemoradiotherapy if receiving Total Neoadjuvant Therapy). Those patients who do not have a stoma, will also complete those questionnaires yearly for 5years post chemoradiotherapy.

Eligibility
Key inclusion criteria
1. Age 18 years or older
2. Biopsy proven locally advanced rectal adenocarcinoma:
o Locally advanced disease defined as: T3 AND N0-2, T1-2 AND N1-2 [Based on AJCC UICC 2017]
o Locally advanced disease defined by the presence of EMVI on MRI, regardless of T or N stage.
3. Subject to undergo Long Course Neoadjuvant Chemo-Radiotherapy based on a multidisciplinary meeting recommendation
4. Considered suitable for long course pelvic radiation therapy
5. Considered suitable for surgery
6. Considered suitable for MRI
7. Willing and able to comply with all study requirements, including treatment and follow up assessments
8. Signed, written informed consent.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Presence of metastatic disease (M1)
2. T4 disease based on AJCC 2017
3. Local recurrence of previously treated rectal cancer
4. Previous pelvic radiotherapy
5. Contraindication to fluoropyrimidine chemotherapy
6. History of another malignancy:
a. Patients with a past history of adequately treated carcinoma-in-situ, basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or superficial transitional cell carcinoma of the bladder are eligible. Patients with a history of other malignancies are eligible if they have been continuously disease free for at least 5 years after definitive primary treatment.
7. Concurrent illness, including severe infection that may jeopardize the ability of the patient to undergo the chemoradiation with reasonable safety
8. Presence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol including chemoradiation and/or follow-up schedule.
9. Pregnancy or lactation.

Study design
Purpose of the study
Educational / counselling / training
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Who is / are masked / blinded?



Intervention assignment
Other design features
Phase
Not Applicable
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
23/01/2019
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
125
Accrual to date
124
Final
Recruitment in Australia
Recruitment state(s)
NSW,NT,SA

Funding & Sponsors
Funding source category [1] 301741 0
Other Collaborative groups
Name [1] 301741 0
Australian Gastro-intestinal Trials Group
Country [1] 301741 0
Australia
Primary sponsor type
Government body
Name
Southern Adelaide Local Health Network Inc
Address
Flinders Medical Centre
Flinders Drive
Bedford Park
SA 5042
Country
Australia
Secondary sponsor category [1] 301482 0
None
Name [1] 301482 0
Address [1] 301482 0
Country [1] 301482 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 302461 0
Southern Adelaide Clinical Human Research Ethics
Ethics committee address [1] 302461 0
Ethics committee country [1] 302461 0
Australia
Date submitted for ethics approval [1] 302461 0
Approval date [1] 302461 0
09/10/2018
Ethics approval number [1] 302461 0

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 90298 0
Prof Chris Karapetis
Address 90298 0
Flinders Medical Centre
Flinders Drive
Bedford Park
SA 5042
Country 90298 0
Australia
Phone 90298 0
+61 8 82046151
Fax 90298 0
Email 90298 0
[email protected]
Contact person for public queries
Name 90299 0
Kate Richardson
Address 90299 0
Flinders Medical Centre
Flinders Drive
Bedford Park
SA 5042
Country 90299 0
Australia
Phone 90299 0
+61 8 82044481
Fax 90299 0
Email 90299 0
[email protected]
Contact person for scientific queries
Name 90300 0
Kate Richardson
Address 90300 0
Flinders Medical Centre
Flinders Drive
Bedford Park
SA 5042
Country 90300 0
Australia
Phone 90300 0
+61 8 82044481
Fax 90300 0
Email 90300 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Not in the ethical submission, plan and approval


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
SourceTitleYear of PublicationDOI
EmbaseNeoadjuvant Therapy for Locally Advanced Rectal Cancer: Recent Advances and Ongoing Challenges.2021https://dx.doi.org/10.1016/j.clcc.2020.12.005
EmbaseA longitudinal cohort study of watch and wait in complete clinical responders after chemo-radiotherapy for localised rectal cancer: study protocol.2022https://dx.doi.org/10.1186/s12885-022-09304-x
N.B. These documents automatically identified may not have been verified by the study sponsor.