Clinical trial NCT01459328: Resource-Sparing Curative Treatment for Rectal Cancer
Official title: Resource-Sparing Curative Treatment for Rectal Cancer
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Rectal Carcinoma
Keywords: rectal carcinoma
long course chemo-radiation
short course chemo-rdiation
Locally Advanced Rectal Carcinoma
Lead sponsor: International Atomic Energy Agency
Sponsor class: OTHER_GOV
Collaborators: name: Centre Anti Cancer Hopital Frantz Fanon
name: Hospital A.C. Camargo
name: Credit Valley Hospital
name: Instituto Nacional de Cancerologia, Columbia
name: University Hospital Sestre Milosrdnice
name: Minesterio de Cienca, Tecnologia y Medio Ambiente
name: V.N. Cancer Center GKNM Hospital
name: Tata Memorial Hospital
name: Dr Cipto Mangunkusumo General Hospital
name: National Cancer Center, Bratislava
name: University of Cape Town
name: Catholic University of the Sacred Heart
First posted: 2011-10-25
Enrollment: 350
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: 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.

Eligibility criteria: 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)

Primary outcomes:
measure: Overall Survival
timeFrame: From commencement of radiation (day 1) to death or last follow-up up to 5 years.
Secondary outcomes:
measure: Biological Effect and Tumour Biology
timeFrame: Prior to surgical decision in weeks 13-15 and 4 weeks after surgery
measure: Quality of Life
timeFrame: From date of randomization till the end of follow-up (5 years)
measure: Health-related Economics
timeFrame: From date of randomization till the end of follow-up (5 years)
Other outcomes:
Locations:
city: Blida
country: Algeria
facility: Centre Anti-Cancer, Hopital Franz Fanon
city: Sao Paulo
country: Brazil
facility: Hospital A.C. Camargo, Fundacao Antonio Prudente
city: Mississauga
country: Canada
facility: Credit Valley Hospital
state: Ontario
city: Bogota D.C.
country: Colombia
facility: Instituto Nacional de Cancerologia, Minesterio de Salud
city: Zagreb
country: Croatia
facility: Department of Oncology and Nuclear Medicine, University Hospital Sestre Milosrdnice
city: La Habana
country: Cuba
facility: Ministerio de Cienca, Tecnologia y Medio Ambiente (CITMA)
city: Coimbatore
country: India
facility: Department of Radiation Oncology, V.N. Cancer Center, GKNM Hospital
city: Mumbai
country: India
facility: Department of Radiation Oncology, Tata Memorial Hospital
city: Jakarta
country: Indonesia
facility: Department of Radiotherapy, Dr. Cipto Mangunkusuma National General Hospital, University of Indonesia
city: Roma
country: Italy
facility: Instituto di Radiologia, Universita Cattolica del Sacro Cuore
city: Bratislava
country: Slovakia
facility: National Cancer Institute
city: Cape Town
country: South Africa
facility: University of Cape Town
Study officials:
affiliation: International Atomic Energy Agency
name: Eduardo Rosenblatt
role: PRINCIPAL_INVESTIGATOR
References:
citation: Bosset JF, Collette L, Calais G, Mineur L, Maingon P, Radosevic-Jelic L, Daban A, Bardet E, Beny A, Ollier JC; EORTC Radiotherapy Group Trial 22921. Chemotherapy with preoperative radiotherapy in rectal cancer. N Engl J Med. 2006 Sep 14;355(11):1114-23. doi: 10.1056/NEJMoa060829.
citation: Kapiteijn E, Marijnen CA, Nagtegaal ID, Putter H, Steup WH, Wiggers T, Rutten HJ, Pahlman L, Glimelius B, van Krieken JH, Leer JW, van de Velde CJ; Dutch Colorectal Cancer Group. Preoperative radiotherapy combined with total mesorectal excision for resectable rectal cancer. N Engl J Med. 2001 Aug 30;345(9):638-46. doi: 10.1056/NEJMoa010580.
citation: Radu C, Berglund A, Pahlman L, Glimelius B. Short-course preoperative radiotherapy with delayed surgery in rectal cancer - a retrospective study. Radiother Oncol. 2008 Jun;87(3):343-9. doi: 10.1016/j.radonc.2007.11.025. Epub 2008 Feb 21.
citation: Braendengen M, Tveit KM, Berglund A, Birkemeyer E, Frykholm G, Pahlman L, Wiig JN, Bystrom P, Bujko K, Glimelius B. Randomized phase III study comparing preoperative radiotherapy with chemoradiotherapy in nonresectable rectal cancer. J Clin Oncol. 2008 Aug 1;26(22):3687-94. doi: 10.1200/JCO.2007.15.3858.