Resource-Sparing Curative Treatment for Rectal Cancer

Phase 3

• Conditions: Rectal Carcinoma

• 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.

Study Timeline

• Study Start: 2009-09
• Status Verified: 2011-10
• Study First Submitted: 2011-10-10
• Study First Submitted QC: 2011-10-24
• Last Update Submitted: 2011-10-24
• Study First Posted: 2011-10-25
• Last Update Posted: 2011-10-25
• Primary Completion: 2013-09

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 350

Inclusion Criteria

• 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

Exclusion Criteria

• 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

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 results
Quality 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)

Centre Anti-Cancer, Hopital Franz Fanon; 🇩🇿 Blida, Algeria

Hospital A.C. Camargo, Fundacao Antonio Prudente; 🇧🇷 Sao Paulo, Brazil

Credit Valley Hospital; 🇨🇦 Mississauga, Ontario, Canada

Instituto Nacional de Cancerologia, Minesterio de Salud; 🇨🇴 Bogota D.C., Colombia

Department of Oncology and Nuclear Medicine, University Hospital Sestre Milosrdnice; 🇭🇷 Zagreb, Croatia

Ministerio de Cienca, Tecnologia y Medio Ambiente (CITMA); 🇨🇺 La Habana, Cuba

Department of Radiation Oncology, V.N. Cancer Center, GKNM Hospital; 🇮🇳 Coimbatore, India

Department of Radiation Oncology, Tata Memorial Hospital; 🇮🇳 Mumbai, India

Department of Radiotherapy, Dr. Cipto Mangunkusuma National General Hospital, University of Indonesia; 🇮🇩 Jakarta, Indonesia

Instituto di Radiologia, Universita Cattolica del Sacro Cuore; 🇮🇹 Roma, Italy

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