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

NCT04095299 | Recruiting Phase 3

• 1 other identifier: WW3
• Study Type: interventional
• Target: 162
• Locations: 1 country
• Sites: 5

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.

Conditions

Cancer of Rectum

Outcome Measures

Primary Outcomes (1)

• 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

  2 years after start of treatment

Secondary Outcomes (7)

• Rate of complete response within four months from start of radiotherapy

  4 months

• Locoregional recurrence (within the pelvis)

  At least yearly up to 5 years

• Relapse free survival

  At least yearly up to 5 years

• Overall survival

  At least yearly up to 5 years

• Colostomy-free survival

  At least yearly up to 5 years

Study Arms (2)

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.

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

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

Interventions

50.4 Gy to the tumor and elective volume RADIATION

Standard radiotherapy

A: Standard chemoradiotherapy

Capecitabine 825 mg/m2 twice daily on weekdays DRUG

Standard chemotherapy

A: Standard chemoradiotherapy; B: High-dose radiotherapy

62 Gy to the clinical tumor volume and 50.4 Gy to the elective volume RADIATION

Experimental radiotherapy

B: High-dose radiotherapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Vejle Hospital: lead

Study Sites (5)

Aalborg University Hospital

Aalborg, Denmark

RECRUITING

Copenhagen University Hospital, Righshospitalet and Bispebjerg Hospital

Copenhagen, Denmark

RECRUITING

Zealand University Hospital, Næstved

Næstved, Denmark

RECRUITING

Zealand University Hospital, Roskilde

Roskilde, Denmark

RECRUITING

Department of Oncology, Vejle Hospital

Vejle, Denmark

RECRUITING

MeSH Terms

Conditions

Rectal Neoplasms

Interventions

Capecitabine

Condition Hierarchy (Ancestors)

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Lars H Jensen, MD, PhD

  Department of Oncology, Vejle Hospital - University Hospital of Southern Denmark

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Lars H Jensen, MD, PhD

CONTACT

+45 7940 6802; lars.henrik.jensen@rsyd.dk

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: September 17, 2019
• First Posted: September 19, 2019
• Study Start: January 20, 2020
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2033
• Last Updated: January 8, 2026

Record last verified: 2026-01

Locations

DK (5)