"Watch and Wait" After Neo-adjuvant Chemoradiotherapy for Primary Locally Advanced Rectal Cancer. (NORWAIT)

"Watch and Wait" in Patients With Complete Clinical Response (cCR) After Neo-adjuvant Chemoradiotherapy for Primary Locally Advanced Rectal Cancer.

Among patients treated for locally advanced rectal cancer with neo-adjuvant radio-chemotherapy, about 15% will have complete clinical response in terms of no visible tumor or ulcerations on the site of the primary tumor, or whitening of the rectal wall or telangiectasia. In this Norwegian national multicenter observational study, patients with complete clinical response (cCR) after neo-adjuvant treatment for rectal cancer as defined by national guidelines, will be invited to a Watch&Wait program with a specially designed follow-up in order to see if the tumor has disappeared permanently, or if there is regrowth of the tumor. Primary endpoint is the true regrowth rate in an unselected national cohort of patients.

Study Overview

• Status: Recruiting
• Conditions: Rectal Cancer

• Study Type: Observational
• Enrollment (Anticipated): 100

Contacts and Locations

• Study Contact: Name: Hartwig Kørner, MD, PhD; Phone Number: 51518000; Email: hartwig.korner@uib.no

Study Locations

• Norway
  • Bergen, Norway
    • Recruiting
    • Haukeland University Hospital
    • Contact: Frank Pfeffer, MD, PhD; Phone Number: +4755975000; Email: frank.pfeffer@helse-bergen.no
  • Kristiansand, Norway
    • Recruiting
    • Sørlandet Hospital Kristiansand
    • Contact: Christian Kersten, MD; Phone Number: +4791503738; Email: Christian.Kersten@sshf.no
  • Lørenskog, Norway, 1478
    • Recruiting
    • Akershus University Hospital
    • Contact: Arne Færden, MD PhD; Phone Number: +4767960000; Email: Arne.Engebreth.Faerden@ahus.no
  • Oslo, Norway
    • Recruiting
    • Oslo University Hospital
    • Contact: Gro Wiedswang, MD PhD; Phone Number: +4722118080; Email: gro.wiedswang@gmail.com
  • Stavanger, Norway
    • Recruiting
    • Stavanger University Hospital
    • Contact: Hartwig Kørner, MD, PhD; Phone Number: 51518000; Email: hartwig.korner@uib.no
  • Tromsø, Norway
    • Recruiting
    • University Hospital Northern Norway
    • Contact: Stig Norderval, MD PhD; Phone Number: +4777626000; Email: stig.norderval@unn.no
  • Trondheim, Norway
    • Recruiting
    • St. Olavs Hospital
    • Contact: William J. Lossius, MD; Phone Number: +4772573000; Email: William.J.Lossius@stolav.no

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

All patients in Norway with rectal cancer treated with neo-adjuvant radio-chemotherapy according to Norwegian national guidelines, who have complete clinical response at 6-12 weeks after fulfilled treatment

Description

Inclusion Criteria:

• Histologically verified adenocarcinoma of the rectum within 15 cm from the anal verge measured by rigid proctoscopy
• Patients who have completed neoadjuvant treatment according to national guidelines for rectal cancer, i.e., radiotherapy or chemo-radiotherapy (at least 40 Gy) or short-course radiotherapy combined with chemotherapy
• Patients aged ≥18 years of age are eligible for inclusion. However, patients aged ≤40 years are recommended to undergo surgery on the theoretical base of a possibly more aggressive tumour disease in this age group, and will be asked to participate in the study by consenting to recording of data. Those patients who insist on W&W approach after careful consideration and well-documented informed consent are eligible for entering the W&W protocol.
• Given informed consent
• Stage I-III rectal cancer; however, patients with limited liver metastases who undergo primary liver surgery as part of a "liver first" treatment approach may be included

Exclusion Criteria:

• Patients without cCR
• Patients unable to give informed consent
• Patients with short course radiotherapy (5x5 Gy) without additional chemotherapy, or patients receiving less than 40 Gy in long course CRT
• Patients with cCR but with increasing tumour growth on MRI after preoperative treatment
• Patients with metastatic disease at the time of diagnosis with the exception of those who are eligible for "liver first" treatment approach as part of an intention to cure approach.
• Patients previously diagnosed and treated for malignant disease in the pelvic region with radio- or chemoradiotherapy
• Other circumstances that may interfere with successful participation in the W&W protocol

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of regrowth	rate of regrowth of tumor after initial complete clinical response (cCR) in patients who undergo a specially designed Watch & Wait program and without surgical removal of the rectum; to determine the positive predictive value of cCR.	Baseline to 5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The rate of cCR after preoperative CRT	To calculate the rate of cCR in an national unselected cohort	Baseline to 5 years
Metachronous distant metastases in patients following the W&W protocol	To calculate the rate of the occurrence of distant metastases in patients who undergo the watch & Wait program	Baseline to 5 years
Overall and cancer-specific survival protocol compared to patients with ypCR, i.e. patients with complete pathologic response after resection.	To analyse the overall and cancer-specific survival of patients with cCR following the W&W	Baseline to 5 years
Patient-reported outcome measures - rectal function (LARS) and quality of life (QoL)	To evaluate the effect of the Watch and wait program on rectal function by using the Low anterior resection syndrome (LARS) score	Baseline to 5 years
Patient-reported outcome measures - quality of life (LARS) and quality of life (QoL)	To measure the effect of the Watch and wait program on quality of life by using the EORTC QLQ C30	Baseline to 5 years
Sensitivity, specificity and overall diagnostic accuracy of MRI with regard to the diagnosis of complete response	To compare the regression grade obtained by multi parametric MRI protocol to the clinical diagnose of complete response at baseline, i.e. clinical diagnosis of complete response	Baseline to 5 years
Diagnostic accuracy of MRI to detect regrowth during follow-up after complete response	To compare the accuracy of multi parametric MRI protocol with clinical examination during follow-up with regard to possible regrowth of the tumour	Baseline to 5 years

Collaborators and Investigators

• Sponsor: Helse Stavanger HF
• Collaborators: University Hospital of North Norway; Sorlandet Hospital HF; St. Olavs Hospital; University Hospital, Akershus; Helse-Bergen HF; Cancer Registry of Norway; Oslo universitetssykehus HF
• Investigators: Principal Investigator: Hartwig Kørner, MD, PhD, Helse Stavanger HF

Study record dates

Study Major Dates

• Study Start (ACTUAL): January 10, 2018
• Primary Completion (ANTICIPATED): December 31, 2023
• Study Completion (ANTICIPATED): December 31, 2028

Study Registration Dates

• First Submitted: January 10, 2018
• First Submitted That Met QC Criteria: January 17, 2018
• First Posted (ACTUAL): January 18, 2018

Study Record Updates

• Last Update Posted (ACTUAL): December 17, 2020
• Last Update Submitted That Met QC Criteria: December 15, 2020
• Last Verified: October 1, 2020

More Information

Terms related to this study

• Keywords: locally advanced, neo-adjuvant treatment, Watch & Wait
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Rectal Neoplasms
• Other Study ID Numbers: SUSID674

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No