Resource-Sparing Curative Treatment for Rectal Cancer

Rectal Carcinoma Clinical Trial

Official title:

Resource-Sparing Curative Treatment for Rectal Cancer

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01459328
• Other study ID #: E33034
• Status: Recruiting
• Phase: Phase 3
• First received: October 10, 2011
• Last updated: October 24, 2011
• Start date: September 2009

Study information

• Verified date: October 2011
• Source: International Atomic Energy Agency
• Contact: IAEA
• Is FDA regulated: No
• Health authority: United Nations: International Atomic Energy Agency
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Recruiting
• Enrollment: 350
• Est. primary completion date: September 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Rectal Carcinoma
• Rectal Neoplasms

Intervention

Radiation:
• Radiotherapy
Short course radiotherapy: 25Gy in 5 daily fractions over 1 week Chemotherapy: - Bolus 5 Fluorouracil 450 mg/m2/day Injected Leucovorin 20 mg/m2/day for 5 days
• Radiotherapy
Conventional long course chemo-radiation: Radiation 50Gy in 25 daily fractions over 5 weeks Bolus 5 Fluorouracil 350mg/m2/d for 5 days Injected Leucovorin 20mg in both the first and last (5th) week of radiation Oral Capecitabine (CAPE) 825mg/m2 b.i.d. during the entire radiotherapy course over 5 weeks.

Locations

Country	Name	City	State
Algeria	Centre Anti-Cancer, Hopital Franz Fanon	Blida
Brazil	Hospital A.C. Camargo, Fundacao Antonio Prudente	Sao Paulo
Canada	Credit Valley Hospital	Mississauga	Ontario
Colombia	Instituto Nacional de Cancerologia, Minesterio de Salud	Bogota D.C.
Croatia	Department of Oncology and Nuclear Medicine, University Hospital Sestre Milosrdnice	Zagreb
Cuba	Ministerio de Cienca, Tecnologia y Medio Ambiente (CITMA)	La Habana
India	Department of Radiation Oncology, V.N. Cancer Center, GKNM Hospital	Coimbatore
India	Department of Radiation Oncology, Tata Memorial Hospital	Mumbai
Indonesia	Department of Radiotherapy, Dr. Cipto Mangunkusuma National General Hospital, University of Indonesia	Jakarta
Italy	Instituto di Radiologia, Universita Cattolica del Sacro Cuore	Roma
Slovakia	National Cancer Institute	Bratislava
South Africa	University of Cape Town	Cape Town

Sponsors (13)

Lead Sponsor

Collaborator

International Atomic Energy Agency

Catholic University of the Sacred Heart, Centre Anti Cancer Hopital Frantz Fanon, Credit Valley Hospital, Dr Cipto Mangunkusumo General Hospital, Hospital A.C. Camargo, Instituto Nacional de Cancerologia, Columbia, Minesterio de Cienca, Tecnologia y Medio Ambiente, National Cancer Center, Bratislava, Tata Memorial Hospital, University Hospital "Sestre milosrdnice", University of Cape Town, V.N. Cancer Center GKNM Hospital

Countries where clinical trial is conducted

Algeria,  Brazil,  Canada,  Colombia,  Croatia,  Cuba,  India,  Indonesia,  Italy,  Slovakia,  South Africa, 

References & Publications (4)

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. Erratum in: N Engl J Med. 2007 Aug 16;357(7):728. — View Citation

Braendengen M, Tveit KM, Berglund A, Birkemeyer E, Frykholm G, Påhlman L, Wiig JN, Byström 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. — View 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. — View Citation

Radu C, Berglund A, Påhlman L, Glimelius B. Short-course preoperative radiotherapy with delayed surgery in rectal cancer - a retrospective study. Radiother Oncol. 2008 Jun;87(3):343-9. Epub 2008 Feb 21. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Survival		From commencement of radiation (day 1) to death or last follow-up up to 5 years.	No
Secondary	Biological Effect and Tumour Biology	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	Prior to surgical decision in weeks 13-15 and 4 weeks after surgery	No
Secondary	Quality of Life		From date of randomization till the end of follow-up (5 years)	No
Secondary	Health-related Economics	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)	From date of randomization till the end of follow-up (5 years)	No