Cancer of RectumPhase 3WW3NCT04095299
Standard Dose Versus High Dose of Radiotherapy in Rectal Preservation With Chemo-radiotherapy in Rectal Cancer Patients
A Phase 3 study testing 50.4 Gy to the tumor and elective volume, 62 Gy to the clinical tumor volume and 50.4 Gy to the elective volume and Capecitabine 825 mg/m2 twice daily on weekdays in people with Cancer of Rectum, run by Vejle Hospital at 5 sites in Denmark.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Cancer of Rectum
- What is being tested?
- 50.4 Gy to the tumor and elective volume, 62 Gy to the clinical tumor volume and 50.4 Gy to the elective volume and Capecitabine 825 mg/m2 twice daily on weekdays
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 162 participants
- Where
- 5 sitesDenmark
- Study dates
- 20 Jan 2020to Dec 2033
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Show all 14Show fewer
- 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
Who cannot join
- 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
Trial locations and contacts
5 sites in 1 country. Contact the study team or a site near you to ask about taking part.
5 sites in 1 country
Denmark5 sites, 5 recruiting
- Recruiting
Aalborg University Hospital
Aalborg
- Recruiting
Copenhagen University Hospital, Righshospitalet and Bispebjerg Hospital
Copenhagen
- Recruiting
Zealand University Hospital, Næstved
Næstved
- Recruiting
Zealand University Hospital, Roskilde
Roskilde
- Recruiting
Department of Oncology, Vejle Hospital
Vejle
Lars H Jensen, MD, PhD, lars.henrik.jensen@rsyd.dk
About this study
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)
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.
Read the 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.
- Conditions
- Cancer of Rectum
- Being tested
- 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
- Medical subject headings
- Rectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
50.4 Gy to the tumor and elective volumeRadiation
Standard radiotherapy
62 Gy to the clinical tumor volume and 50.4 Gy to the elective volumeRadiation
Experimental radiotherapy
Capecitabine 825 mg/m2 twice daily on weekdaysDrug
Standard chemotherapy
| Study group | Role | What they receive |
|---|---|---|
| A: Standard chemoradiotherapy | Active comparator | 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. Receives: Radiation: 50.4 Gy to the tumor and elective volume; Drug: Capecitabine 825 mg/m2 twice daily on weekdays |
| B: High-dose radiotherapy | Experimental | 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 Receives: Radiation: 62 Gy to the clinical tumor volume and 50.4 Gy to the elective volume; Drug: Capecitabine 825 mg/m2 twice daily on weekdays |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 2 years after start of treatment
Secondary outcomes (7)
Rate of complete response within four months from start of radiotherapy
Measured: 4 months
Locoregional recurrence (within the pelvis)
Measured: At least yearly up to 5 years
Relapse free survival
Measured: At least yearly up to 5 years
Overall survival
Measured: At least yearly up to 5 years
Colostomy-free survival
Measured: At least yearly up to 5 years
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.
Measured: Up to 5 years
Frequency of grade 3-4 toxicity according to CTCAE v4
Measured: Up to 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Sep 2019
- Study start20 Jan 2020
- Primary completionDec 2026 (estimated)
- Study completionDec 2033 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Cancer of RectumStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Enrollment will continue until 162 patients have reached the primary endpoint two years after start of treatment. During these two years the total number of patients will therefore expectedly increase to approximately 290. This will be the population for secondary analyses and long-term follow-up.
- Masking
- None (open label)
- Enrolment
- 162 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Vejle Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Lars H Jensen, MD, PhD, Principal investigator, Department of Oncology, Vejle Hospital - University Hospital of Southern Denmark
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04095299
- Sponsor's protocol ID
- WW3
- Acronym
- WW3
- Status last verified
- Jan 2026
- First submitted
- 17 Sep 2019
- Last updated
- 8 Jan 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 8 Jan 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT04095299
- Acronym / sponsor ID
- WW3 / WW3
- Conditions
- Cancer of Rectum
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 162 participants (estimated)
- Lead sponsor
- Vejle HospitalUniversity, hospital or other
- Study start
- 20 Jan 2020 (actual)
- Primary completion
- Dec 2026 (estimated)
- Study completion
- Dec 2033 (estimated)
- First posted
- 19 Sep 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Enrollment will continue until 162 patients have reached the primary endpoint two years after start of treatment. During these two years the total number of patients will therefore expectedly increase to approximately 290. This will be the population for secondary analyses and long-term follow-up.
| Arm | Type | Receives |
|---|---|---|
| A: Standard chemoradiotherapy | Active comparator | Radiation: 50.4 Gy to the tumor and elective volume, Drug: Capecitabine 825 mg/m2 twice daily on weekdays50.4 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. |
| B: High-dose radiotherapy | Experimental | Radiation: 62 Gy to the clinical tumor volume and 50.4 Gy to the elective volume, Drug: Capecitabine 825 mg/m2 twice daily on weekdays62 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 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- Histopathologically verified adenocarcinoma of the rectum
- MDT conference finds patient a candidate for rectal resection
- Clinical tumor category cT1-3
- MRI findings
- Performance status 0-2
Key exclusion criteria (6 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 50.4 Gy to the tumor and elective volumeStandard radiotherapy | Radiation | A: Standard chemoradiotherapy |
| 62 Gy to the clinical tumor volume and 50.4 Gy to the elective volumeExperimental radiotherapy | Radiation | B: High-dose radiotherapy |
| Capecitabine 825 mg/m2 twice daily on weekdaysStandard chemotherapy | Drug | A: Standard chemoradiotherapy, B: High-dose radiotherapy |
Primary outcome
Rectal preservation at two years
Time frame: 2 years after start of treatment
* 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
7 secondary outcomes
Rate of complete response within four months from start of radiotherapy
Time frame: 4 months
Locoregional recurrence (within the pelvis)
Time frame: At least yearly up to 5 years
Relapse free survival
Time frame: At least yearly up to 5 years
Overall survival
Time frame: At least yearly up to 5 years
Colostomy-free survival
Time frame: At least yearly up to 5 years
Quality of life as assessed ny the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ) CR29+C30
Time frame: Up to 5 years
Frequency of grade 3-4 toxicity according to CTCAE v4
Time frame: Up to 5 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Jan 2026.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Lars H Jensen, MD, PhD principal investigator
Department of Oncology, Vejle Hospital - University Hospital of Southern Denmark
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing 50.4 Gy to the tumor and elective volume, 62 Gy to the clinical tumor volume and 50.4 Gy to the elective volume and Capecitabine 825 mg/m2 twice daily on weekdays in people with Cancer of Rectum, run by Vejle Hospital at 5 sites in Denmark.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 14 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 8 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in Denmark. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Lars H Jensen, MD, PhD (+45 7940 6802, lars.henrik.jensen@rsyd.dk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Rectal preservation at two years (time frame: 2 years after start of treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Jan 2026.