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

Vejle Hospital

Status and phase: Enrolling; Phase 3

Conditions: Cancer of Rectum

Treatments: Radiation: 50.4 Gy to the tumor and elective volume; 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

Study type: Interventional

Funder types: Other

Identifiers

NCT04095299

WW3

Details and patient eligibility

About

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.

Full 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.

Enrollment: 162 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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162 participants in 2 patient groups

A: Standard chemoradiotherapy

Active Comparator group

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.

Treatment:

Drug: Capecitabine 825 mg/m2 twice daily on weekdays

Radiation: 50.4 Gy to the tumor and elective volume

B: High-dose radiotherapy

Experimental group

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

Treatment:

Drug: Capecitabine 825 mg/m2 twice daily on weekdays

Radiation: 62 Gy to the clinical tumor volume and 50.4 Gy to the elective volume