Clinical trial NCT03125343: Watch and Wait as Treatment for Patients With Rectal Cancer
Official title: A Multicenter Prospective National Cohort Study for Patients With Advanced Rectal Cancer - is it Possible to Induce Remission and Avoid Surgery - Watch and Wait?
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Rectal Neoplasms
Keywords: radiotherapy
chemotherapy
complete response
Lead sponsor: Sahlgrenska University Hospital
Sponsor class: OTHER
Collaborators: name: Karolinska Institutet
First posted: 2017-04-24
Enrollment: 400
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Intervention model description: All patients with complete response defined as described above will be offered to enter the study
Primary purpose: TREATMENT

Brief summary: A national cohort study with all patients scheduled for neoadjuvant treatment with (chemo)radiotherapy or short course radiotherapy with delayed surgery 6-8 weeks) for rectal cancer staged as cT4bNX/anycTanycN and cMRF+/anycTanycN and lateral lymph nodes on MRI (and patients that have been offered short course raditotherapy with delayed surgery due to various reasons). The tumours are positioned midrectal or low and are palpable with the finger. The patients offered this treatment after recommendations on their local multidisciplinary tumour board will be will be informed and offered to participate in the study. Patients scheduled for short course radiotherapy with immediate surgery cannot be included.

Detailed description: • Biopsies and blood from patients with rectal cancer subject to neoadjuvant treatment with (chemo)radiotherapy or radiotherapy 5x5 Gy with at least 6-8 weeks wait until surgery. All patients will be asked to answer a QoL questionnaire (appendix C) to cover their experiences of the neaodajvuant treatment. (Answered at diagnosis and at evaluation of treatment and decision of surgery or inclusion in the Watch and Wait part of the study).

All patients will undergo scheduled (chemo)radiotherapy according to national guidelines. The patients with chemoradiotherapy will be evaluated at 8-10 weeks after completed treatment (25) with pelvic MRI. After this evaluation at 8-10 weeks patients with suspected complete response or near complete response will examined according to the protocol below.

All patients that are considered to have complete response will be offered a "Watch and wait" approach with follow-up according to the protocol. They will then be followed at one of the Regional University Hospitals within their catchment are.

All patients with a palpable rectal cancer staged as cT4bNX/anycTanycN and cMRF+/anycTanycN and lateral lymph nodes on MRI (and patients that have been offered short course raditotherapy with delayed surgery due to various reasons) that does not achieve complete response will serve as control and will be treated with surgery as planned prior to initiation of (chemo)radiotherapy.

Patients with indication of complete response on follow-up MRI will undergo endoscopy, and digital rectal examination to ascertain complete response. MRI together with documentation from endoscopy will be reviewed at the Regional University Hospital to extablish agreement regarding interpretation. All the below mentioned criteria must be fullfilled to be considered complete response:

1. No suspicious metastatic lymph nodes or evidence of remaining tumour on MRI. In the majority of cases a complete response on MRI will be seen as areas of homogeneous fibrosis. Absence of any remaining pathological tissue is seen in a minority of cases.
2. Endoscopic examination with light/white mucosa or scar, telangiectasies. Prescence of fibrosis and oedema.
3. No palpable tumour on clinical examination (26).

In the spring of 2023 200 pts included. An amendment was sent to the ethical review board to enable continued inclusion while the initial 200 pts are analyzed. This has been approved and the study has thus planned continuation for another 2-3 years.

Eligibility criteria: Inclusion Criteria:

All patients in Sweden with a palpable rectal cancer staged as cT4bNX/anycTanycN and cMRF+/anycTanycN and lateral lymph nodes on MRI considered appropriate for 5x5 Gy and 6-8 weeks of wait prior to surgery according to Stockholm III (28) or a palpable rectal cancer staged as cT4bNX/anycTanycN and cMRF+/anycTanycN and lateral lymph nodes on MRI a planned schedule for CRT according to the Swedish National Program for rectal cancer scheduled for neoadjuvant therapy are possible to include.

The study includes two parts, where part one is optional in including hospitals. The aim of the biopsy substudy to identify tumour and plasma markers for complete response, thus all patients that will receive (chemo)radiotherapy in the neoadjuvant setting are included to provide a control for the biopsies.

For the WoW part of the study all patients that achieve complete response after neoadjuvant treatment according to the specified criteria above can be included in the Watch and Wait protocol. In detail this includes patients with:

Midrectal or low rectal cancers that are palpable and considered with an indication of 5x5 Gy and long wait (6-8 weeks) (the indication for waiting may be logistics, co-morbidity, advanced age):

* cT4bNX
* anycTanycN and cMRF+ anycTanycN and lateral lymph nodes on MRI

Exclusion Criteria:

* No informed consent received for participation.
* Patients with rectal cancer that is scheduled for (chemo) radiotherapy but is not palpable during rectal examination (10-15 cm) as this cannot be examined by digital examination and followed as scheduled.
* Contraindication for MRI such as presence of non compatible metallic implants or claustrophobia.

Primary outcomes:
measure: 3-year disease free survival.
timeFrame: 3 years
Secondary outcomes:
measure: Percentage re-growth during follow-up
timeFrame: 10 years
measure: Local recurrence after salvage surgery due to regrowth
timeFrame: 10 years
measure: Results after surgery for re-growth
timeFrame: 10 years
measure: Long-term survival
timeFrame: 10 years
measure: Number of patients with no response, partial response and complete response.
timeFrame: Accrual period - probably 4 years
measure: Anorectal function measured by LARS score
timeFrame: 5 years
measure: Quality of life measured by a clinometric approach
timeFrame: up to 24 months
measure: Health economic evaluation
timeFrame: 5 years
Other outcomes:
Locations:
city: Gothenburg
country: Sweden
facility: Dept. of Surgery, Sahlgrenska University Hospital/Ostra
city: Stockholm
country: Sweden
facility: Karolinska Institutet
Study officials:
affiliation: Sahlgrenska Academy at Gothenburg University
name: Eva Angenete, M.D., Ph.D.
role: PRINCIPAL_INVESTIGATOR
References: