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Watch and Wait as Treatment for Patients With Rectal Cancer (WoW)

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ClinicalTrials.gov Identifier: NCT03125343
Recruitment Status : Recruiting
First Posted : April 24, 2017
Last Update Posted : September 18, 2019
Sponsor:
Collaborator:
Karolinska Institutet
Information provided by (Responsible Party):
Eva Angenete, Sahlgrenska University Hospital, Sweden

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.

Condition or disease Intervention/treatment Phase
Rectal Neoplasms Procedure: endoscopy Procedure: Surgery Device: MRI Not Applicable

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).

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 200 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Intervention Model Description: All patients with complete response defined as described above will be offered to enter the study
Masking: None (Open Label)
Primary Purpose: Treatment
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?
Actual Study Start Date : January 2017
Estimated Primary Completion Date : April 2021
Estimated Study Completion Date : April 2024

Arm Intervention/treatment
Experimental: 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.
Procedure: 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

Device: MRI
Active Comparator: 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.
Procedure: Surgery
Surgery according to recommendations from the multidisciplinary group in patients that prefer surgery to a watch and wait strategy

Device: MRI



Primary Outcome Measures :
  1. 3-year disease free survival. [ Time Frame: 3 years ]
    Thus this includes patients that have had regrowth and been operated for their tumour. Includes metastastic surgery as well


Secondary Outcome Measures :
  1. Percentage re-growth during follow-up [ Time Frame: 10 years ]
    Endoscopic or MRI indication of regrowth

  2. Local recurrence after salvage surgery due to regrowth [ Time Frame: 10 years ]
    Local recurrence as shown by MRI, endoscopy or digital examination

  3. Results after surgery for re-growth [ Time Frame: 10 years ]
    Complications and mortality after surgery

  4. Long-term survival [ Time Frame: 10 years ]
    Overall survival

  5. Number of patients with no response, partial response and complete response. [ Time Frame: Accrual period - probably 4 years ]
    Number of patients in each group - no response, partial response and complete response

  6. Anorectal function measured by LARS score [ Time Frame: 5 years ]
    Anorectal function measured by LARS and then compared to patients operated.

  7. Quality of life measured by a clinometric approach [ Time Frame: up to 24 months ]
    QoL measurments sent to patients

  8. Health economic evaluation [ Time Frame: 5 years ]
    A cost efficiency analysis



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03125343


Contacts
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Contact: Eva Angenete, M.D., Ph.D. eva.angenete@vgregion.se

Locations
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Sweden
Dept. of Surgery, Sahlgrenska University Hospital/Ostra Recruiting
Gothenburg, Sweden, SE 416 85
Contact: Eva Angenete, MD,PhD    +46313438410    eva.angenete@vgregion.se   
Karolinska Institutet Recruiting
Stockholm, Sweden
Contact: Anna Martling, Professor         
Sponsors and Collaborators
Sahlgrenska University Hospital, Sweden
Karolinska Institutet
Investigators
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Principal Investigator: Eva Angenete, M.D., Ph.D. Sahlgrenska Academy at Gothenburg University

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Responsible Party: Eva Angenete, M.D, Ph.D., Sahlgrenska University Hospital, Sweden
ClinicalTrials.gov Identifier: NCT03125343     History of Changes
Other Study ID Numbers: WoW
First Posted: April 24, 2017    Key Record Dates
Last Update Posted: September 18, 2019
Last Verified: September 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Eva Angenete, Sahlgrenska University Hospital, Sweden:
radiotherapy
chemotherapy
complete response
Additional relevant MeSH terms:
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Rectal Neoplasms
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Intestinal Diseases
Rectal Diseases