Watch and Wait as Treatment for Patients With Rectal Cancer

NCT ID: NCT03125343

Last Updated: 2023-11-07

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 400 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-01-31
• Study Completion Date: 2028-12-31

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.

Conditions

Rectal Neoplasms

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

No surgery

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 establish agreement regarding interpretation.

Group Type: EXPERIMENTAL

endoscopy

Intervention Type: PROCEDURE

Continuous follow-up. All patients with complete response will be followed for ten years. Details from the follow-up schedule will be registered in clinical record forms including information on the endoscopic findings, MRI findings and digital examination.

They will be followed ever third month for the first two years as follows:

• PET-CT is optional, but can be performed at inclusion
• Pelvic MRI including diffusion weighted imaging according to appendix C.
• Clinical examination
• Endoscopy (flexible sigmoidoskopy) with photodocumentation
• CEA

After two years the patients will be followed every six month with:

• Pelvic MRI including diffusion weighted imaging according to appendix as at baseline
• Clinical examination
• Endoscopy with photodocumentation
• CEA

MRI

Intervention Type: DEVICE

Surgery

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 establish agreement regarding interpretation. Patients with complete response will be offered watch and wait strategy, but the patients that want surgery will be operated according to the multi disciplinary conference decision.

Group Type: ACTIVE_COMPARATOR

Surgery

Intervention Type: PROCEDURE

Surgery according to recommendations from the multidisciplinary group in patients that prefer surgery to a watch and wait strategy

MRI

Intervention Type: DEVICE

Interventions

endoscopy

Continuous follow-up. All patients with complete response will be followed for ten years. Details from the follow-up schedule will be registered in clinical record forms including information on the endoscopic findings, MRI findings and digital examination.

They will be followed ever third month for the first two years as follows:

• PET-CT is optional, but can be performed at inclusion
• Pelvic MRI including diffusion weighted imaging according to appendix C.
• Clinical examination
• Endoscopy (flexible sigmoidoskopy) with photodocumentation
• CEA

After two years the patients will be followed every six month with:

• Pelvic MRI including diffusion weighted imaging according to appendix as at baseline
• Clinical examination
• Endoscopy with photodocumentation
• CEA

Intervention Type: PROCEDURE

Surgery

Surgery according to recommendations from the multidisciplinary group in patients that prefer surgery to a watch and wait strategy

Intervention Type: PROCEDURE

MRI

Intervention Type: DEVICE

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Karolinska Institutet

OTHER

Sponsor Role: collaborator

Sahlgrenska University Hospital

OTHER

Sponsor Role: lead

Responsible Party

Eva Angenete

M.D, Ph.D.

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Eva Angenete, M.D., Ph.D.

Role: PRINCIPAL_INVESTIGATOR

Sahlgrenska Academy at Gothenburg University

Locations

Dept. of Surgery, Sahlgrenska University Hospital/Ostra

Gothenburg, , Sweden

Site Status: RECRUITING

Karolinska Institutet

Stockholm, , Sweden

Site Status: RECRUITING

Countries

Sweden

Central Contacts

Eva Angenete, M.D., Ph.D.

Role: CONTACT

eva.angenete@vgregion.se

Facility Contacts

Eva Angenete, MD,PhD

Role: primary

eva.angenete@vgregion.se

+46313438410

Anna Martling, Professor

Role: primary

Other Identifiers

WoW

Identifier Type: -

Identifier Source: org_study_id