Resource-Sparing Curative Treatment for Rectal Cancer
- Conditions
- Rectal Carcinoma
- Interventions
- Radiation: Radiotherapy
- Registration Number
- NCT01459328
- Lead Sponsor
- International Atomic Energy Agency
- Brief Summary
This is a prospective, multicentre, randomized clinical trial comparing two different neo-adjuvant radiation-based strategies prior to intended surgery for locally advanced adenocarcinoma of the rectum.
This trial may establish the investigational therapy to be superior to, or at least not inferior to conventional treatment.
- Detailed Description
This phase III randomised clinical trial compares the outcome of two different neo-adjuvant radiation based treatments for locally advanced rectal carcinoma. This encompasses patients at risk for a positive circumfrential resection margin (CRM+) on baseline assessment imaging and pateints identified as being with a T-descriptor T4 at baseline assessment.
The arms compared are as follows:
* The investigational arm: short chemo-radiation course(25Gy in 5 daily fractions over 1 week) +/- surgery.
* The conventional arm: protracted chemo-radiation course (50Gy in 25 daily fractions over 5 weeks combined with chemotherapy)+/- surgery.
The outcomes include four domains: overall survival, biological effect, quality of life and health-related economics.
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- All
- Target Recruitment
- 350
- 18 years of age or older
- Clinical (i.e. surgical determination) and/or diagnostic image findings consistent with c/uT4 or CRM+ (note that CRM+ must be established by MRI), primary rectal Adenocarcinoma (i.e. histology consistent with origin from rectal mucosa); these constitute LARC for the purpose of this protocol
- Treatment will be directed at the primary cancer, being clinically appropriate and given with an initial intent to cure the patient (this includes accepting up front that radiation and surgery are feasible; for surgery, this means that the patient has been determined fit for major surgery by an anaesthesiologist prior to the request for randomization)
- Performance status is sufficient to undertake the treatment in either arm (KPS>50%)
- Patient is accessible for required follow-up and data collection
- Radiation oncologist expects survival to exceed 6 months from date of diagnosis
- Patient provides informed consent
- Recurrent rectal cancer
- Primary wholly in the sigmoid colon
- Considered to be arising in the anal canal
- Metastatic disease beyond the pelvis (by clinical assessment and/or diagnostic imaging)
- Contraindications to protocol RT or to protocol chemotherapy, such as one or more of the following:
- any prior RT to the pelvis; a solitary pelvic kidney within the intended radiation volume
- consideration by the most responsible radiation oncologist that the treatment volume is too large, or the amount of small bowel or other critical organs within the treatment volume is too much for safe treatment
- significantly abnormal laboratory tests such as impaired renal/liver function
- a haemoglobin that is < 8.0 (or 80, SI) and the patient is not transfused to exceed 8.0 (or 80, SI)
- on-going medications that are not compatible with protocol neo-adjuvant chemotherapy as described in this protocol
- Significant development issues (such as with age < 18 yr)
- Co-morbidity
- Psychiatric diagnosis
- Physical impairment
- Pregnancy or continuing breast-feeding, that precludes administration of protocol treatments, or that precludes data collection (such as likely to preclude follow-up visits or completing questionnaires)
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm A: Conventional Long Course Chemo-Radiation Radiotherapy Conventional long course chemo-radiation Arm B: Short Course Radiation Followed by Chemotherapy Radiotherapy Experimental short course radiation followed by chemotherapy.
- Primary Outcome Measures
Name Time Method Overall Survival From commencement of radiation (day 1) to death or last follow-up up to 5 years.
- Secondary Outcome Measures
Name Time Method Biological Effect and Tumour Biology Prior to surgical decision in weeks 13-15 and 4 weeks after surgery Maximum size of the tumor based on imaging and/or up to 3D measures reported by radiologists, comparing baseline and pre-surgical decision inverstigations
If definitive surgery is conducted:
* Proportion obtaining R0
* Proportion undergoing TME
* Status of the neurovascular and neural invasion(s)
* Nodal ratio
* Tumor sizes
CEA resultsQuality of Life From date of randomization till the end of follow-up (5 years) Health-related Economics From date of randomization till the end of follow-up (5 years) Number of days in hospital
Number of surgical procedures
Number of days with stomas
Protocol required therapies, as actually administered
Adverse events that have significant cost implications (i.e. cost-drivers)
Trial Locations
- Locations (12)
Ministerio de Cienca, Tecnologia y Medio Ambiente (CITMA)
🇨🇺La Habana, Cuba
Department of Oncology and Nuclear Medicine, University Hospital Sestre Milosrdnice
🇭🇷Zagreb, Croatia
Department of Radiation Oncology, Tata Memorial Hospital
🇮🇳Mumbai, India
Department of Radiation Oncology, V.N. Cancer Center, GKNM Hospital
🇮🇳Coimbatore, India
National Cancer Institute
🇸🇰Bratislava, Slovakia
Instituto di Radiologia, Universita Cattolica del Sacro Cuore
🇮🇹Roma, Italy
Hospital A.C. Camargo, Fundacao Antonio Prudente
🇧🇷Sao Paulo, Brazil
Instituto Nacional de Cancerologia, Minesterio de Salud
🇨🇴Bogota D.C., Colombia
Centre Anti-Cancer, Hopital Franz Fanon
🇩🇿Blida, Algeria
Credit Valley Hospital
🇨🇦Mississauga, Ontario, Canada
University of Cape Town
🇿🇦Cape Town, South Africa
Department of Radiotherapy, Dr. Cipto Mangunkusuma National General Hospital, University of Indonesia
🇮🇩Jakarta, Indonesia