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

Phase 3RecruitingNCT04095299

Vejle Hospital162 enrolled

Overview

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.

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 Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (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

Outcomes

Primary Outcomes

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

Time frame: 2 years after start of treatment

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

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

Frequency of grade 3-4 toxicity according to CTCAE v4

Time frame: Up to 5 years

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

Overview

Conditions

Interventions

Eligibility

Locations (5)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts