Rectal CarcinomaPhase 3NCT01459328
Resource-Sparing Curative Treatment for Rectal Cancer
A Phase 3 study testing Radiotherapy in people with Rectal Carcinoma, run by International Atomic Energy Agency at 12 sites in 11 countries.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Rectal Carcinoma
- What is being tested?
- Radiotherapy
- Type of treatment
- Pill or oral medicine, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 350 participants
- Where
- 12 sitesin 11 countries
- Study dates
- Sep 2009to Sep 2013
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 15Show fewer
- 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)
Trial locations and contacts
12 sites in 11 countries.
IAEA contact
12 sites in 11 countries
India2 sites, 2 recruiting
- Recruiting
Department of Radiation Oncology, V.N. Cancer Center, GKNM Hospital
Coimbatore, Tamil Nadu 641 037
Nagarajan Murugaiyan, +9104222216715, mnagarajan@gknmh.org
mnr81@yahoo.com
- Recruiting
Department of Radiation Oncology, Tata Memorial Hospital
Mumbai, Maharashtra 400 012
Reena Engineer, +912224177163, reena_engineer@rediffmail.com
+912224177000
Algeria1 site, 1 recruiting
- Recruiting
Centre Anti-Cancer, Hopital Franz Fanon
Blida, 09000
Boualga Kada, +213 25 415985, kboualga2002@yahoo.fr
Boualga Kada
Brazil1 site, 1 recruiting
- Recruiting
Hospital A.C. Camargo, Fundacao Antonio Prudente
São Paulo, 01509-010
Maria Leticia Gobo Silva, +551132729613, mlgobo@yahoo.fr
Maria Leticia Gobo Silva
Canada1 site, 1 recruiting
- Recruiting
Credit Valley Hospital
Mississauga, Ontario, L5M 2N1
Jidong Lian, ombudsman@cvh.on.ca
Jidong Lian
Colombia1 site, 1 recruiting
- Recruiting
Instituto Nacional de Cancerologia, Minesterio de Salud
Bogota D.C.
Rosalba Ospinp Pena, 005713341997, rospino@cancer.gov.co
Rosalba Ospino Pena
Croatia1 site, 1 recruiting
- Recruiting
Department of Oncology and Nuclear Medicine, University Hospital Sestre Milosrdnice
Zagreb, 10000
Ana Frobe, +38513787468, afrobe@irb.hr
Blanka Jaksic
Cuba1 site, 1 recruiting
- Recruiting
Ministerio de Cienca, Tecnologia y Medio Ambiente (CITMA)
La Habana
Maria Lourdes Pernez Pena, +5378316040, soconcol@infomed.sld.cu
Aixa Ulloa Balmaseda
Indonesia1 site, 1 recruiting
- Recruiting
Department of Radiotherapy, Dr. Cipto Mangunkusuma National General Hospital, University of Indonesia
Jakarta, 10430
Sri Mutya Sekarutami, +62213921155, smutya12@yahoo.com
Sri Mutya Sekarutami
Italy1 site, 1 recruiting
- Recruiting
Instituto di Radiologia, Universita Cattolica del Sacro Cuore
Roma, 00168
Vincenzo Valentini, +390630154376, vvalentini.it@email.it
Vincenzo Valentini
Slovakia1 site, 1 recruiting
- Recruiting
National Cancer Institute
Bratislava, 833 10
Margita Pobijakova, +421259378579, margita.pobijakova@nou.sk
Margita Pobijakova
South Africa1 site, 1 recruiting
- Recruiting
University of Cape Town
Cape Town, 7701
Barbara Robertson, Barbara.robertson@uct.ac.za
Barbara Robertson
About this study
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.
Read the 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.
- Conditions
- Rectal Carcinoma
- Being tested
- Radiotherapy
- Keywords
- rectal carcinoma, long course chemo-radiation, short course chemo-rdiation, Locally Advanced Rectal Carcinoma
- Medical subject headings
- Rectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RadiotherapyRadiation
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
RadiotherapyRadiation
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.
| Study group | Role | What they receive |
|---|---|---|
| Arm A: Conventional Long Course Chemo-Radiation | Active comparator | Conventional long course chemo-radiation Receives: Radiation: Radiotherapy |
| Arm B: Short Course Radiation Followed by Chemotherapy | Experimental | Experimental short course radiation followed by chemotherapy. Receives: Radiation: Radiotherapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall Survival
Measured: From commencement of radiation (day 1) to death or last follow-up up to 5 years.
Secondary outcomes (3)
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
Measured: Prior to surgical decision in weeks 13-15 and 4 weeks after surgery
Quality of Life
Measured: From date of randomization till the end of follow-up (5 years)
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)
Measured: From date of randomization till the end of follow-up (5 years)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Oct 2011 (estimated)
- Study startSep 2009
- Primary completionSep 2013 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Rectal CarcinomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 350 participants (estimated)
Sponsor and investigators
- Lead sponsor
- International Atomic Energy Agency
- Sponsor type
- Other government
- Collaborators
- Centre Anti Cancer Hopital Frantz Fanon, Hospital A.C. Camargo, Credit Valley Hospital, Instituto Nacional de Cancerologia, Columbia, University Hospital Sestre Milosrdnice, Minesterio de Cienca, Tecnologia y Medio Ambiente, V.N. Cancer Center GKNM Hospital, Tata Memorial Hospital, Dr Cipto Mangunkusumo General Hospital, National Cancer Center, Bratislava, University of Cape Town, Catholic University of the Sacred Heart
- Responsible party
- Sponsor
- Investigators
- Eduardo Rosenblatt, Principal investigator, International Atomic Energy Agency
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01459328
- Sponsor's protocol ID
- E33034
- Status last verified
- Oct 2011
- First submitted
- 10 Oct 2011
- Last updated
- 25 Oct 2011
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 16971718Kapiteijn 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.
PubMed 11547717Radu 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.
PubMed 18093674Braendengen 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.
PubMed 18669453
Study at a glance
From the registry record, last updated by the sponsor on 25 Oct 2011. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Resource-Sparing Curative Treatment for Rectal Cancer
- ClinicalTrials.gov ID
- NCT01459328
- Acronym / sponsor ID
- E33034
- Conditions
- Rectal Carcinoma
- Keywords
- rectal carcinoma, long course chemo-radiation, short course chemo-rdiation, Locally Advanced Rectal Carcinoma
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 350 participants (estimated)
- Lead sponsor
- International Atomic Energy AgencyOther government
- Collaborators
- Centre Anti Cancer Hopital Frantz Fanon, Hospital A.C. Camargo, Credit Valley Hospital, Instituto Nacional de Cancerologia, Columbia, University Hospital Sestre Milosrdnice, Minesterio de Cienca, Tecnologia y Medio Ambiente, V.N. Cancer Center GKNM Hospital, Tata Memorial Hospital, Dr Cipto Mangunkusumo General Hospital, National Cancer Center, Bratislava, University of Cape Town, Catholic University of the Sacred Heart
- Study start
- Sep 2009
- Primary completion
- Sep 2013 (estimated)
- First posted
- 25 Oct 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm A: Conventional Long Course Chemo-Radiation | Active comparator | Radiation: RadiotherapyConventional long course chemo-radiation |
| Arm B: Short Course Radiation Followed by Chemotherapy | Experimental | Radiation: RadiotherapyExperimental short course radiation followed by chemotherapy. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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
Key exclusion criteria (15 listed)
- 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:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RadiotherapyShort 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 | Radiation | Arm B: Short Course Radiation Followed by Chemotherapy |
| RadiotherapyConventional 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. | Radiation | Arm A: Conventional Long Course Chemo-Radiation |
Primary outcome
Overall Survival
Time frame: From commencement of radiation (day 1) to death or last follow-up up to 5 years.
3 secondary outcomes
Biological Effect and Tumour Biology
Time frame: Prior to surgical decision in weeks 13-15 and 4 weeks after surgery
Quality of Life
Time frame: From date of randomization till the end of follow-up (5 years)
Health-related Economics
Time frame: From date of randomization till the end of follow-up (5 years)
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Oct 2011.
- Background: PubMed 16971718Bosset 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.
- Background: PubMed 11547717Kapiteijn 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.
- Background: PubMed 18093674Radu 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.
- Background: PubMed 18669453Braendengen 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
IAEA contact
Eduardo Rosenblatt principal investigator
International Atomic Energy Agency
12 sites in 11 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Radiotherapy in people with Rectal Carcinoma, run by International Atomic Energy Agency at 12 sites in 11 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 25 Oct 2011. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 12 sites in India, Algeria, Brazil, Canada, Colombia and 6 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact IAEA, or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall Survival (time frame: From commencement of radiation (day 1) to death or last follow-up up to 5 years.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01459328, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Oct 2011.