Colorectal CancerPhase 2EXPERT-CNCT00383695
Oxaliplatin, Capecitabine, and Radiation Therapy With or Without Cetuximab in Treating Patients Undergoing Surgery for High-Risk Rectal Cancer
A Phase 2 study testing cetuximab, capecitabine and oxaliplatin in people with Colorectal Cancer, run by Royal Marsden NHS Foundation Trust at 13 sites in 3 countries.
Trial summary
RATIONALE: Drugs used in chemotherapy, such as oxaliplatin and capecitabine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Colorectal Cancer
- What is being tested?
- cetuximab, capecitabine and oxaliplatin
- Type of treatment
- Surgery or procedure
- How many people
- 164 participants
- Where
- 13 sitesin 3 countries
- Study dates
- Sep 2005to not given
- Phase
- Phase 2
- 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
DISEASE CHARACTERISTICS:
- Histologically confirmed adenocarcinoma or undifferentiated non-small cell carcinoma of the rectum
- MRI-defined high-risk, operable disease, defined by ≥ 1 of the following:
- Tumors within 1 mm of mesorectal fascia (i.e., circumferential resection margin threatened or involved)
- T3 tumors at or below levators
- Tumors extending ≥ 5 mm into perirectal fat
- T4 tumors
- Presence of extramural venous invasion (primary tumor is therefore at least T3)
- No evidence of metastatic disease by CT scan of the chest and abdomen or, if required, by positron emission tomography scan or biopsy
- No rectal cancer that is unlikely to be operable even after neoadjuvant treatment (i.e., tumor involving the internal iliac vessels)
- No T1-2 rectal cancer, in the absence of other high-risk factors
- T2 tumors within 1 mm of mesorectal fascia allowed
- No recurrent disease
PATIENT CHARACTERISTICS:
- WHO performance status 0-2
- Life expectancy > 3 months
- WBC > 3,000/mm³
- Absolute neutrophil count > 1,500/mm³
- Platelet count > 100,000/mm³
- Bilirubin < 1.5 times upper limit of normal (ULN)
- Transaminases < 2.5 times ULN
- Creatinine normal OR creatinine clearance > 50 mL/min
- Not pregnant or nursing
- Fertile patients must use effective contraception
- No concurrent uncontrolled medical condition
- No other active malignant disease within the past 10 years except nonmelanoma skin cancer or carcinoma in situ of the cervix
- No contraindications to MRI (e.g., pacemaker)
- No medical or psychiatric conditions that would preclude informed consent
- No known malabsorption syndrome or lack of physical integrity of the upper gastrointestinal tract
- No clinically significant (i.e., active) cardiac disease, including any of the following:
- Congestive heart failure
- Symptomatic coronary artery disease
- Cardiac dysrhythmia (e.g., atrial fibrillation, even if controlled with medication)
- Myocardial infarction within the past 12 months
- No symptoms or history of peripheral neuropathy
PRIOR CONCURRENT THERAPY:
- No prior chemotherapy, radiotherapy, or investigational treatment for rectal cancer
- No other concurrent cytotoxic agents or investigational drugs
- No concurrent sorivudine or sorivudine analogues (e.g., brivudine)
Trial locations and contacts
13 sites in 3 countries.
13 sites in 3 countries
United Kingdom8 sites
Royal Bournemouth Hospital NHS Trust
Bournemouth, England, BH7 7DW
Sussex Cancer Centre at Royal Sussex County Hospital
Brighton, England, BN2 5BE
Eastbourne District General Hospital
Eastbourne, England, BN21 2UD
Cancer Research UK Clinical Groups at Guy's King's & St. Thomas' Hospitals
London, England, SE5 9NU
Mid Kent Oncology Centre at Maidstone Hospital
Maidstone, England, ME16 9QQ
Dorset Cancer Centre
Poole Dorset, England, BH15 2JB
Southampton General Hospital
Southampton, England, SO16 6YD
Royal Marsden - Surrey
Sutton, England, SM2 5PT
Spain3 sites
Vall d'Hebron University Hospital
Barcelona, 08035
Hospital Universitario La Paz
Madrid, 28046
Hospital Clinico Universitario de Valencia
Valencia, 46010
Sweden2 sites
Karolinska University Hospital - Solna
Stockholm, S-171 76
Uppsala University Hospital
Uppsala, S-75185
About this study
Official title: A Multicentre Randomised Phase II Clinical Trial Comparing Oxaliplatin (Eloxatin), Capecitabine (Xeloda) and Pre-Operative Radiotherapy With or Without Cetuximab Followed by Total Mesorectal Excision for the Treatment of Patients With Magnetic Resonance Imaging (MRI) Defined High Risk Rectal Cancer
RATIONALE: Drugs used in chemotherapy, such as oxaliplatin and capecitabine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Monoclonal antibodies, such as cetuximab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Giving chemotherapy and radiation therapy with or without cetuximab before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. It is not yet known whether giving oxaliplatin, capecitabine, and radiation therapy is more effective with or without cetuximab when given before surgery in treating rectal cancer.
PURPOSE: This randomized phase II trial is studying oxaliplatin, capecitabine, and radiation therapy to compare how well they work with or without cetuximab in treating patients undergoing surgery for high-risk rectal cancer.
Read the detailed description
OBJECTIVES:
- Compare the pathological complete response rate at total mesorectal excision in patients with high-risk rectal cancer treated with neoadjuvant therapy comprising oxaliplatin, capecitabine, and radiotherapy with or without cetuximab.
OUTLINE: This is a multicenter, open-label, randomized, controlled study. Patients are stratified according to participating center and presence of T4 disease (yes vs no). Patients are randomized to 1 of 2 treatment arms.
- Arm I:
- Neoadjuvant chemotherapy: Patients receive oxaliplatin IV over 2 hours on days 1, 22, 43, and 64 and oral capecitabine twice daily on days 1-14, 22-35, 43-56, and 64-77.
- Neoadjuvant chemoradiotherapy: Patients undergo radiotherapy once daily on days 85-89, 92-96, 99-103, 106-110, 113-117, and 120-124 and receive oral capecitabine twice daily on days 85-126.
- Surgery: Four to six weeks after completion of chemoradiotherapy, patients undergo total mesorectal excision (TME).
- Adjuvant therapy: Beginning 6-8 weeks after surgery, patients receive oxaliplatin IV over 2 hours on days 1, 22, 43, and 64 and oral capecitabine twice daily on days 1-14, 22-35, 43-56, and 64-77.
- Arm II:
- Neoadjuvant therapy: Patients receive oxaliplatin and capecitabine as in arm I neoadjuvant chemotherapy and cetuximab IV over 1-2 hours on days 1, 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78.
- Neoadjuvant chemoradiotherapy: Patients undergo radiotherapy and receive capecitabine as in arm I neoadjuvant chemoradiotherapy and cetuximab IV over 1 hour on days 85, 92, 99, 106, 113, and 120.
- Surgery: Four to six weeks after completion of chemoradiotherapy patients undergo TME as in arm I.
- Adjuvant therapy: Beginning 6-8 weeks after surgery, patients receive oxaliplatin and capecitabine as in arm I adjuvant chemotherapy and cetuximab IV over 1 hour on days 1, 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78.
In both arms, treatment continues in the absence of disease progression or unacceptable toxicity.
Quality of life is assessed periodically.
After completion of study treatment, patients are followed every 3 months for 1 year, every 6 months for 2 years, and then annually for 2 years.
PROJECTED ACCRUAL: A total of 164 patients will be accrued for this study.
- Conditions
- Colorectal Cancer
- Being tested
- cetuximab, capecitabine, oxaliplatin, adjuvant therapy, conventional surgery
- Keywords
- adenocarcinoma of the rectum, stage I rectal cancer, stage II rectal cancer, stage III rectal cancer
- Medical subject headings
- Colorectal Neoplasms, Rectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
cetuximabBiological
capecitabineDrug
oxaliplatinDrug
adjuvant therapyProcedure or surgery
conventional surgeryProcedure or surgery
neoadjuvant therapyProcedure or surgery
radiation therapyRadiation
What is being measured
The primary outcome is the main question the study is designed to answer.
Pathological complete response rate at time of total mesorectal excision (TME)
Secondary outcomes (12)
Radiological response rates after completion of neoadjuvant therapy
Complete resection rate (R0 resection) with microscopic clear resection margin (tumor observed > 1 mm from the resection margin), especially circumferential resection margin
Perioperative measures, including operation time, duration of in-patient stay, perioperative transfusion requirement, and mortality, within 30 days of TME
Postoperative complications, including wound infection, wound dehiscence, and fistula formation
Quality of TME as assessed by audit of photographed surgical specimens
Rate of abdominoperitoneal excision
Rate of permanent defunctioning colostomies
Clinical and radiological anastomotic leak rate
Progression-free survival and patterns of failure
Overall survival
Safety
Quality of life, including long-term bowel function
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Oct 2006 (estimated)
- Study startSep 2005
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Colorectal CancerStudies of the same condition, open and under way.
- More trials run by Royal Marsden NHS Foundation TrustThe sponsor's other registered studies.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Masking
- None (open label)
- Enrolment
- 164 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Royal Marsden NHS Foundation Trust
- Sponsor type
- University, hospital or other
- Investigators
- David Cunningham, MD, Study chair, Royal Marsden NHS Foundation Trust
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00383695
- Sponsor's protocol ID
- CDR0000503948
- Other IDs
- RMNHS-RMH-CCR-2553, EU-20635, EUDRACT-2004-004707-38, CRUK-EXPERT-C, MERCK-RMNHS-RMH-CCR-2553
- Acronym
- EXPERT-C
- Status last verified
- Jan 2010
- First submitted
- 29 Sep 2006
- Last updated
- 13 Jan 2010
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 13 Jan 2010. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multicentre Randomised Phase II Clinical Trial Comparing Oxaliplatin (Eloxatin), Capecitabine (Xeloda) and Pre-Operative Radiotherapy With or Without Cetuximab Followed by Total Mesorectal Excision for the Treatment of Patients With Magnetic Resonance Imaging (MRI) Defined High Risk Rectal Cancer
- ClinicalTrials.gov ID
- NCT00383695
- Acronym / sponsor ID
- EXPERT-C / CDR0000503948
- Conditions
- Colorectal Cancer
- Keywords
- adenocarcinoma of the rectum, stage I rectal cancer, stage II rectal cancer, stage III rectal cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 164 participants (estimated)
- Lead sponsor
- Royal Marsden NHS Foundation TrustUniversity, hospital or other
- Study start
- Sep 2005
- First posted
- 3 Oct 2006 (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.
RATIONALE: Drugs used in chemotherapy, such as oxaliplatin and capecitabine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Monoclonal antibodies, such as cetuximab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Giving chemotherapy and radiation therapy with or without cetuximab before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. It is not yet known whether giving oxaliplatin, capecitabine, and radiation therapy is more effective with or without cetuximab when given before surgery in treating rectal cancer.
PURPOSE: This randomized phase II trial is studying oxaliplatin, capecitabine, and radiation therapy to compare how well they work with or without cetuximab in treating patients undergoing surgery for high-risk rectal cancer.
Detailed description
OBJECTIVES:
- Compare the pathological complete response rate at total mesorectal excision in patients with high-risk rectal cancer treated with neoadjuvant therapy comprising oxaliplatin, capecitabine, and radiotherapy with or without cetuximab.
OUTLINE: This is a multicenter, open-label, randomized, controlled study. Patients are stratified according to participating center and presence of T4 disease (yes vs no). Patients are randomized to 1 of 2 treatment arms.
- Arm I:
- Neoadjuvant chemotherapy: Patients receive oxaliplatin IV over 2 hours on days 1, 22, 43, and 64 and oral capecitabine twice daily on days 1-14, 22-35, 43-56, and 64-77.
- Neoadjuvant chemoradiotherapy: Patients undergo radiotherapy once daily on days 85-89, 92-96, 99-103, 106-110, 113-117, and 120-124 and receive oral capecitabine twice daily on days 85-126.
- Surgery: Four to six weeks after completion of chemoradiotherapy, patients undergo total mesorectal excision (TME).
- Adjuvant therapy: Beginning 6-8 weeks after surgery, patients receive oxaliplatin IV over 2 hours on days 1, 22, 43, and 64 and oral capecitabine twice daily on days 1-14, 22-35, 43-56, and 64-77.
- Arm II:
- Neoadjuvant therapy: Patients receive oxaliplatin and capecitabine as in arm I neoadjuvant chemotherapy and cetuximab IV over 1-2 hours on days 1, 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78.
- Neoadjuvant chemoradiotherapy: Patients undergo radiotherapy and receive capecitabine as in arm I neoadjuvant chemoradiotherapy and cetuximab IV over 1 hour on days 85, 92, 99, 106, 113, and 120.
- Surgery: Four to six weeks after completion of chemoradiotherapy patients undergo TME as in arm I.
- Adjuvant therapy: Beginning 6-8 weeks after surgery, patients receive oxaliplatin and capecitabine as in arm I adjuvant chemotherapy and cetuximab IV over 1 hour on days 1, 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78.
In both arms, treatment continues in the absence of disease progression or unacceptable toxicity.
Quality of life is assessed periodically.
After completion of study treatment, patients are followed every 3 months for 1 year, every 6 months for 2 years, and then annually for 2 years.
PROJECTED ACCRUAL: A total of 164 patients will be accrued for this study.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Masking
- None (open label)
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
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 |
|---|---|---|
| cetuximab | Biological | – |
| capecitabine | Drug | – |
| oxaliplatin | Drug | – |
| adjuvant therapy | Procedure or surgery | – |
| conventional surgery | Procedure or surgery | – |
| neoadjuvant therapy | Procedure or surgery | – |
| radiation therapy | Radiation | – |
Primary outcome
Pathological complete response rate at time of total mesorectal excision (TME)
12 secondary outcomes
Radiological response rates after completion of neoadjuvant therapy
Complete resection rate (R0 resection) with microscopic clear resection margin (tumor observed > 1 mm from the resection margin), especially circumferential resection margin
Perioperative measures, including operation time, duration of in-patient stay, perioperative transfusion requirement, and mortality, within 30 days of TME
Postoperative complications, including wound infection, wound dehiscence, and fistula formation
Quality of TME as assessed by audit of photographed surgical specimens
Rate of abdominoperitoneal excision
Rate of permanent defunctioning colostomies
Clinical and radiological anastomotic leak rate
Progression-free survival and patterns of failure
Overall survival
Safety
Quality of life, including long-term bowel function
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Jan 2010.
Related trials for Colorectal Cancer
Not yet recruitingPhase 1
Hepatic Artery Infusion of Carfilzomib in Participants With Liver Metastatic Disease Previously Treated With Hepatic Artery Infusion Pump Therapy
Colorectal Neoplasms, Neoplasms
Active, not recruiting
Streamlined Geriatric and Oncological Evaluation Based On IC Technology
Breast Cancer, Comorbidities and Coexisting Conditions
RecruitingObservational study
Pre- and On-treatment Multi-omics Profiling of Locally Advanced Rectal Cancer
Rectal Neoplasms
Enrolling by invitationObservational study
Natural History Study of Early Life Exposures in Agriculture (ELEA)
Prostate Cancer, Leukemia
RecruitingPhase 2
Tislelizumab in People With Colorectal Cancer
Colorectal Cancer
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.
David Cunningham, MD study chair
Royal Marsden NHS Foundation Trust
13 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing cetuximab, capecitabine and oxaliplatin in people with Colorectal Cancer, run by Royal Marsden NHS Foundation Trust at 13 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
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 13 Jan 2010. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 13 sites in United Kingdom, Spain, Sweden. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Pathological complete response rate at time of total mesorectal excision (TME). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 13 Jan 2010.