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Standard Dose Versus High Dose of Radiotherapy in Rectal Preservation With Chemo-radiotherapy in Rectal Cancer Patients (WW3)

Primary Purpose

Cancer of Rectum

Status
Recruiting
Phase
Phase 2
Locations
Denmark
Study Type
Interventional
Intervention
50.4 Gy to the tumor and elective volume
62 Gy to the clinical tumor volume and 50.4 Gy to the elective volume
Capecitabine 825 mg/m2 twice daily on weekdays
Sponsored by
Vejle Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Cancer of Rectum

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Histopathologically verified adenocarcinoma of the rectum
  • MDT conference finds patient a candidate for rectal resection
  • Clinical tumor category cT1-3

  • MRI findings

    • Maximal cross-sectional size of 4.5 cm (axial plane relative to the rectum)
    • Lowest edge of tumor located at or below the peritoneal reflection on MRI
  • Performance status 0-2
  • Age ≥ 18 years

  • Eligible for radiotherapy and capecitabine according to investigator, including

    • Adequate function of bone marrow (neutrophils ≥ 1.5 x 10^9/l and thrombocytes ≥ 100 x 10^9/l)
    • Adequate function of liver (ALAT < 2.5 x upper limit of normal, bilirubin < 2.5 x upper limit of normal)
    • Adequate kidney function (Serum creatinine < 1.5 x upper limit of normal or measured GFR > 30 ml/min)
  • Fertile women must present a negative pregnancy test and use secure contraceptives during and three months after treatment
  • Written and orally informed consent

Exclusion Criteria:

  • Previous surgical treatment of the present cancer, including transanal excision of tumor
  • Other malignant disease within the past five years except non-melanoma skin cancer and premalignant lesions such as carcinoma in situ
  • Distant metastases verified by imaging or biopsy, i.e. cM1
  • Previous radiation treatment of the pelvis
  • Pregnant or breastfeeding women.
  • Existing colostomy or ileostomy

Sites / Locations

  • Aalborg University HospitalRecruiting
  • Copenhagen University Hospital, Righshospitalet and Bispebjerg HospitalRecruiting
  • Zealand University Hospital, Næstved
  • Zealand University Hospital, Roskilde
  • Department of Oncology, Vejle HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

A: Standard chemoradiotherapy

B: High-dose radiotherapy

Arm Description

50.4 Gy to the tumor and elective volume. The dose is given in 28 fractions on weekdays concomitantly with capecitabine 825 mg/m2 twice daily on weekdays.

62 Gy to the clinical tumor volume and 50.4 Gy to the elective volume. The dose is given in 28 fractions on weekdays concomitantly with capecitabine 825 mg/m2 twice daily on weekdays

Outcomes

Primary Outcome Measures

Rectal preservation at two years
Presence of a full-length rectum, i.e. no rectal resection. Absence of rectal tumor, malignant lymph nodes or any other tumor deposit or recurrence within the pelvis based on clinical examination, CT and MR No stoma because of side effects to treatment or rectal dysfunction

Secondary Outcome Measures

Rate of complete response within four months from start of radiotherapy
Locoregional recurrence (within the pelvis)
Relapse free survival
Overall survival
Colostomy-free survival
Quality of life as assessed ny the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ) CR29+C30
QLQ is a 30-question assessment of quality of life. Twenty-eight questions are assessed on a scale of 1 (Not at all) to 4 (Very much); 2 questions are assessed on a scale of 1 (very poor) to 7 (excellent). Score range 0- 100. In the function scales, score 100 is best (more function). In the symptom scales, score 100 is worst, (more symptoms). The colorectal cancer module QLQ-CR29 should always be complemented by QLQ-C30. It contains four functional scales and 18 symptom scales. Some scales are dependent on gender and some are for patients with or without a stoma. There are 19 individual items assessed on a scale of 1 (Not at all) to 4 (Very much). Scores are totaled from each item to form the scales, and then normalized to 0-100.
Frequency of grade 3-4 toxicity according to CTCAE v4

Full Information

First Posted
September 17, 2019
Last Updated
June 2, 2023
Sponsor
Vejle Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT04095299
Brief Title
Standard Dose Versus High Dose of Radiotherapy in Rectal Preservation With Chemo-radiotherapy in Rectal Cancer Patients
Acronym
WW3
Official Title
Randomized Trial of Standard Dose Versus High Dose of Radiotherapy in Rectal Preservation With Chemo-radiotherapy to Patients With Early Low and Mid Rectal Cancer: The Watchful Waiting 3 Trial (WW3)
Study Type
Interventional

2. Study Status

Record Verification Date
June 2023
Overall Recruitment Status
Recruiting
Study Start Date
January 20, 2020 (Actual)
Primary Completion Date
December 2027 (Anticipated)
Study Completion Date
December 2028 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Vejle Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
In recent years, an increasing number of retrospective and prospective observational studies have indicated that a subset of rectal cancer patients may avoid surgery if they can achieve a complete response to chemoradiotherapy. Prospective trials, including the previous Danish Watchful Waiting trials (NCT00952926, NCT02438839) in early rectal cancer have demonstrated high levels of organ preservation with dose-escalation, but it is unclear whether this was primarily due to tumor stage or dose level. The aim of the present study is to investigate if a higher dose of radiotherapy is superior compared to a standard dose in patients with early rectal cancer undergoing chemoradiotherapy with curative intent.
Detailed Description
The main curative treatment modality for rectal cancer is surgery, potentially combined with chemotherapy and radiotherapy to lower the risk of local recurrence. In recent years, an increasing number of retrospective and prospective observational studies have indicated that a subset of patients may avoid surgery altogether if they can achieve a complete response to chemoradiotherapy. These studies have mainly focused on locally advanced tumors with a high risk of local recurrence. Smaller, less advanced tumors appear to respond better to chemoradiotherapy, but the optimal treatment for non-surgical management has not been established. Prospective trials, including the previous Danish Watchful Waiting trials (NCT00952926, NCT02438839) in early rectal cancer have demonstrated high levels of organ preservation with dose-escalation, but it is unclear whether this was primarily due to tumor stage or dose level. High-level evidence is currently absent for the question of radiotherapy dose, especially in early stage cancers. The aim of the present study is to investigate if a higher dose of radiotherapy is superior compared to a standard dose in patients with early rectal cancer undergoing chemoradiotherapy with curative intent.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cancer of Rectum

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
111 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
A: Standard chemoradiotherapy
Arm Type
Active Comparator
Arm Description
50.4 Gy to the tumor and elective volume. The dose is given in 28 fractions on weekdays concomitantly with capecitabine 825 mg/m2 twice daily on weekdays.
Arm Title
B: High-dose radiotherapy
Arm Type
Experimental
Arm Description
62 Gy to the clinical tumor volume and 50.4 Gy to the elective volume. The dose is given in 28 fractions on weekdays concomitantly with capecitabine 825 mg/m2 twice daily on weekdays
Intervention Type
Radiation
Intervention Name(s)
50.4 Gy to the tumor and elective volume
Intervention Description
Standard radiotherapy
Intervention Type
Radiation
Intervention Name(s)
62 Gy to the clinical tumor volume and 50.4 Gy to the elective volume
Intervention Description
Experimental radiotherapy
Intervention Type
Drug
Intervention Name(s)
Capecitabine 825 mg/m2 twice daily on weekdays
Intervention Description
Standard chemotherapy
Primary Outcome Measure Information:
Title
Rectal preservation at two years
Description
Presence of a full-length rectum, i.e. no rectal resection. Absence of rectal tumor, malignant lymph nodes or any other tumor deposit or recurrence within the pelvis based on clinical examination, CT and MR No stoma because of side effects to treatment or rectal dysfunction
Time Frame
2 years after start of treatment
Secondary Outcome Measure Information:
Title
Rate of complete response within four months from start of radiotherapy
Time Frame
4 months
Title
Locoregional recurrence (within the pelvis)
Time Frame
At least yearly up to 5 years
Title
Relapse free survival
Time Frame
At least yearly up to 5 years
Title
Overall survival
Time Frame
At least yearly up to 5 years
Title
Colostomy-free survival
Time Frame
At least yearly up to 5 years
Title
Quality of life as assessed ny the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ) CR29+C30
Description
QLQ is a 30-question assessment of quality of life. Twenty-eight questions are assessed on a scale of 1 (Not at all) to 4 (Very much); 2 questions are assessed on a scale of 1 (very poor) to 7 (excellent). Score range 0- 100. In the function scales, score 100 is best (more function). In the symptom scales, score 100 is worst, (more symptoms). The colorectal cancer module QLQ-CR29 should always be complemented by QLQ-C30. It contains four functional scales and 18 symptom scales. Some scales are dependent on gender and some are for patients with or without a stoma. There are 19 individual items assessed on a scale of 1 (Not at all) to 4 (Very much). Scores are totaled from each item to form the scales, and then normalized to 0-100.
Time Frame
Up to 5 years
Title
Frequency of grade 3-4 toxicity according to CTCAE v4
Time Frame
Up to 5 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Histopathologically verified adenocarcinoma of the rectum MDT conference finds patient a candidate for rectal resection Clinical tumor category cT1-3 MRI findings Maximal cross-sectional size of 4.5 cm (axial plane relative to the rectum) Lowest edge of tumor located at or below the peritoneal reflection on MRI Performance status 0-2 Age ≥ 18 years Eligible for radiotherapy and capecitabine according to investigator, including Adequate function of bone marrow (neutrophils ≥ 1.5 x 10^9/l and thrombocytes ≥ 100 x 10^9/l) Adequate function of liver (ALAT < 2.5 x upper limit of normal, bilirubin < 2.5 x upper limit of normal) Adequate kidney function (Serum creatinine < 1.5 x upper limit of normal or measured GFR > 30 ml/min) Fertile women must present a negative pregnancy test and use secure contraceptives during and three months after treatment Written and orally informed consent Exclusion Criteria: Previous surgical treatment of the present cancer, including transanal excision of tumor Other malignant disease within the past five years except non-melanoma skin cancer and premalignant lesions such as carcinoma in situ Distant metastases verified by imaging or biopsy, i.e. cM1 Previous radiation treatment of the pelvis Pregnant or breastfeeding women. Existing colostomy or ileostomy
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Lars H Jensen, MD, PhD
Phone
+45 7940 6802
Email
lars.henrik.jensen@rsyd.dk
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Lars H Jensen, MD, PhD
Organizational Affiliation
Department of Oncology, Vejle Hospital - University Hospital of Southern Denmark
Official's Role
Principal Investigator
Facility Information:
Facility Name
Aalborg University Hospital
City
Aalborg
Country
Denmark
Individual Site Status
Recruiting
Facility Name
Copenhagen University Hospital, Righshospitalet and Bispebjerg Hospital
City
Copenhagen
Country
Denmark
Individual Site Status
Recruiting
Facility Name
Zealand University Hospital, Næstved
City
Næstved
Country
Denmark
Individual Site Status
Not yet recruiting
Facility Name
Zealand University Hospital, Roskilde
City
Roskilde
Country
Denmark
Individual Site Status
Not yet recruiting
Facility Name
Department of Oncology, Vejle Hospital
City
Vejle
Country
Denmark
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Lars H Jensen, MD, PhD
Email
lars.henrik.jensen@rsyd.dk

12. IPD Sharing Statement

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Standard Dose Versus High Dose of Radiotherapy in Rectal Preservation With Chemo-radiotherapy in Rectal Cancer Patients

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