Clinical trial NCT03426397: "Wait-and-see" Policy for Complete Responders After Chemoradiotherapy for Rectal Cancer
Official title: Multicentre Evaluation of the "Wait-and-see" Policy for Complete Responders After Chemoradiotherapy for Rectal Cancer
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Rectal Neoplasms
Keywords: Complete response
Organ preservation
Wait-and-See
Watch-and-Wait
Watchful Waiting
Lead sponsor: The Netherlands Cancer Institute
Sponsor class: OTHER
Collaborators: name: Dutch Cancer Society
First posted: 2018-02-08
Enrollment: 220
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: The population will consist of patients, aged 18 years or older, with rectal cancer who after a long course of CRT or a short course of radiation with a long waiting interval have a clinical complete response (ycT0N0), as determined by MRI (including DWI) and digital rectal examination + endoscopy. Only patients who fulfill the predefined list of criteria for a clinical complete response will be considered eligible for inclusion in the study.

Brief summary: The aim of this prospective observational cohort study is to provide short and long term oncological and functional outcome data on organ preserving treatment in good responders after a standard indication for neoadjuvant (chemo)radiation for rectal cancer.

Detailed description: Standard treatment for patients with locally advanced rectal cancer consists of a long course of (CRT) followed by surgical resection. Although the aim of neoadjuvant treatment in these patients is not organ preservation, but rather to provide improved local control, in the tumour disappears completely. Studies from Maastricht, the UK and Brazil have shown that in selected patients with a clinical complete response after CRT, a "wait-and-see" policy without any surgery could be a safe alternative with comparable long-term outcome and better functional outcome compared to patients who had surgery.

The main objective of the study is to provide short and long term oncological and functional outcome data on organ preserving treatment in good responders after a standard indication for neoadjuvant (chemo)radiation. Additional aims are: to set up a national network with expertise centres in the 'wait-and-see' treatment of rectal cancer; to set up a national registry for organ preservation treatment that will generate more evidence on the management and oncological outcome of patients evaluated and treated with organ preservation and \[3\] to offer through this network to all patients who are considered good candidates this 'wait-and-see' approach using the most up to date tools for selection and follow-up.

Study design: multicenter prospective observational cohort study and implementation study. Study population: The population will consist of patients, aged 18 years or older, with rectal cancer who after a long course of CRT or a short course of radiation with a long waiting interval have a clinical complete response (ycT0N0).

The main study endpoint is 2-year non-regrowth disease-free survival. Secondary endpoints are \[1\] the number of fully operational centres who can deliver high quality organ preserving care in rectal cancer in the Netherlands, \[2\] 2-year regrowth rate, \[3\] 2-year local control, \[4\] 2-year overall survival, \[5\] determination of the optimal follow-up schedule and \[6\] quality of life.

Nature and extent of the burden and risks associated with participation, benefit and group relatedness: In the majority of patients who participate in the study, major surgery and the associated morbidity can be avoided. Although scientific proof shows "wait-and-see" only comes with a small risk with adequate selection and follow up, the exact risk is not yet well established and needs to be confirmed by this study. The benefit-risk ratio for this study is regarded as favourable.

Eligibility criteria: Inclusion Criteria:

* Aged 18 years or older
* Primary rectal cancer (pathologically confirmed)
* Treated with neoadjuvant (chemo)radiotherapy
* Clinical complete response (ycT0N0) to neoadjuvant treatment, as determined clinically (digital rectal examination, endoscopy) and radiologically (diffusion weighted imaging-MRI).
* Informed consent and capability of giving informed consent; before informed consent is obtained the patient will be extensively informed about the fact that 'wait-and-see' instead of conventional surgery is not accepted yet by most physicians and that the risks and benefits from these strategies have not been fully determined yet. These issues will be discussed in the patient information form as well.
* Comprehension of the alternative strategies and risks are clear to the patient (in other words that the patient understands the experimental base of the study).

Exclusion Criteria:

* Recurrent rectal cancer
* Contra-indications for MRI. If MRI is not possible because of contra-indications (e.g. pacemaker) patients will be excluded. MRI is crucial for response evaluation and follow-up and cannot be omitted in patients that follow the 'wait-and-see policy'.
* Unable to understand or read Dutch
* Unable or unwilling to comply to the intensive follow-up schedule

Primary outcomes:
measure: 2-year non-regrowth disease-free survival
timeFrame: 2 years after start of wait-and-see protocol
Secondary outcomes:
measure: Number of fully operational centres
timeFrame: 2 years after start of wait-and-see protocol
measure: 2-year local regrowth rate
timeFrame: 2 years after start of wait-and-see protocol
measure: 2-year local control
timeFrame: 2 years after start of wait-and-see protocol
measure: 2-year overall survival
timeFrame: 2 years after start of wait-and-see protocol
measure: Determination of the optimal follow-up schedule
timeFrame: 2 years after start of wait-and-see protocol
measure: Quality of life
timeFrame: At 3 months, 1 year, 2 years and 5 years after the start of wait-and-see protocol
Other outcomes:
Locations:
city: Antwerp
country: Belgium
facility: Universitair Ziekenhuis Antwerpen
city: Amsterdam
country: Netherlands
facility: Antoni van Leeuwenhoek
city: Amsterdam
country: Netherlands
facility: VU Medisch Centrum
city: Breda
country: Netherlands
facility: Amphia Ziekenhuis
city: Deventer
country: Netherlands
facility: Deventer Ziekenhuis
city: Hoorn
country: Netherlands
facility: Westfriesgasthuis
city: Leeuwarden
country: Netherlands
facility: Leeuwarden Medisch Centrum
city: Leiden
country: Netherlands
facility: Leiden University Medical Center
city: Maastricht
country: Netherlands
facility: Maastricht University Medical Centre
city: Nijmegen
country: Netherlands
facility: Radboud UMC
city: Tilburg
country: Netherlands
facility: Elisabeth Tweesteden Ziekenhuis
city: Utrecht
country: Netherlands
facility: Diakonessenhuis
city: Utrecht
country: Netherlands
facility: Universitair Medisch Centrum Utrecht
city: Zwolle
country: Netherlands
facility: Isala Klinieken
Study officials:
affiliation: Antoni van Leeuwenhoek - Netherlands Cancer Institute
name: Geerard Beets, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Antoni van Leeuwenhoek - Netherlands Cancer Institute
name: Regina Beets -Tan, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: