Clinical trial NCT04095299: Standard Dose Versus High Dose of Radiotherapy in Rectal Preservation With Chemo-radiotherapy in Rectal Cancer Patients
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
Overall status: RECRUITING
Phase: PHASE2
Conditions: Cancer of Rectum
Lead sponsor: Vejle Hospital
Sponsor class: OTHER
First posted: 2019-09-19
Enrollment: 111
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Rectal preservation at two years
timeFrame: 2 years after start of treatment
Secondary outcomes:
measure: Rate of complete response within four months from start of radiotherapy
timeFrame: 4 months
measure: Locoregional recurrence (within the pelvis)
timeFrame: At least yearly up to 5 years
measure: Relapse free survival
timeFrame: At least yearly up to 5 years
measure: Overall survival
timeFrame: At least yearly up to 5 years
measure: Colostomy-free survival
timeFrame: At least yearly up to 5 years
measure: Quality of life as assessed ny the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ) CR29+C30
timeFrame: Up to 5 years
measure: Frequency of grade 3-4 toxicity according to CTCAE v4
timeFrame: Up to 5 years
Other outcomes:
Locations:
city: Aalborg
country: Denmark
facility: Aalborg University Hospital
city: Copenhagen
country: Denmark
facility: Copenhagen University Hospital, Righshospitalet and Bispebjerg Hospital
city: Næstved
country: Denmark
facility: Zealand University Hospital, Næstved
city: Roskilde
country: Denmark
facility: Zealand University Hospital, Roskilde
city: Vejle
country: Denmark
facility: Department of Oncology, Vejle Hospital
Study officials:
affiliation: Department of Oncology, Vejle Hospital - University Hospital of Southern Denmark
name: Lars H Jensen, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: