Back to resultsOxaliplatin, Capecitabine, and Radiation Therapy With or Without Cetuximab in Treating Patients Undergoing Surgery for High-Risk Rectal Cancer (EXPERT-C)
Primary Purpose
Colorectal Cancer
Status
Unknown status
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
cetuximab
capecitabine
oxaliplatin
adjuvant therapy
conventional surgery
neoadjuvant therapy
radiation therapy
Sponsored by
About this trial
This is an interventional treatment trial for Colorectal Cancer focused on measuring adenocarcinoma of the rectum, stage I rectal cancer, stage II rectal cancer, stage III rectal cancer
Eligibility Criteria
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)
Sites / Locations
- Vall d'Hebron University Hospital
- Hospital Universitario La Paz
- Hospital Clinico Universitario de Valencia
- Karolinska University Hospital - Solna
- Uppsala University Hospital
- Royal Bournemouth Hospital NHS Trust
- Sussex Cancer Centre at Royal Sussex County Hospital
- Eastbourne District General Hospital
- Cancer Research UK Clinical Groups at Guy's King's & St. Thomas' Hospitals
- Mid Kent Oncology Centre at Maidstone Hospital
- Dorset Cancer Centre
- Southampton General Hospital
- Royal Marsden - Surrey
Outcomes
Primary Outcome Measures
Pathological complete response rate at time of total mesorectal excision (TME)
Secondary Outcome Measures
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
Full Information
NCT ID
NCT00383695
First Posted
September 29, 2006
Last Updated
January 12, 2010
Sponsor
Royal Marsden NHS Foundation Trust
1. Study Identification
Unique Protocol Identification Number
NCT00383695
Brief Title
Oxaliplatin, Capecitabine, and Radiation Therapy With or Without Cetuximab in Treating Patients Undergoing Surgery for High-Risk Rectal Cancer
Acronym
EXPERT-C
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
Study Type
Interventional
2. Study Status
Record Verification Date
January 2010
Overall Recruitment Status
Unknown status
Study Start Date
September 2005 (undefined)
Primary Completion Date
undefined (undefined)
Study Completion Date
undefined (undefined)
3. Sponsor/Collaborators
Name of the Sponsor
Royal Marsden NHS Foundation Trust
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief 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. 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Colorectal Cancer
Keywords
adenocarcinoma of the rectum, stage I rectal cancer, stage II rectal cancer, stage III rectal cancer
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Masking
None (Open Label)
Allocation
Randomized
Enrollment
164 (Anticipated)
8. Arms, Groups, and Interventions
Intervention Type
Biological
Intervention Name(s)
cetuximab
Intervention Type
Drug
Intervention Name(s)
capecitabine
Intervention Type
Drug
Intervention Name(s)
oxaliplatin
Intervention Type
Procedure
Intervention Name(s)
adjuvant therapy
Intervention Type
Procedure
Intervention Name(s)
conventional surgery
Intervention Type
Procedure
Intervention Name(s)
neoadjuvant therapy
Intervention Type
Radiation
Intervention Name(s)
radiation therapy
Primary Outcome Measure Information:
Title
Pathological complete response rate at time of total mesorectal excision (TME)
Secondary Outcome Measure Information:
Title
Radiological response rates after completion of neoadjuvant therapy
Title
Complete resection rate (R0 resection) with microscopic clear resection margin (tumor observed > 1 mm from the resection margin), especially circumferential resection margin
Title
Perioperative measures, including operation time, duration of in-patient stay, perioperative transfusion requirement, and mortality, within 30 days of TME
Title
Postoperative complications, including wound infection, wound dehiscence, and fistula formation
Title
Quality of TME as assessed by audit of photographed surgical specimens
Title
Rate of abdominoperitoneal excision
Title
Rate of permanent defunctioning colostomies
Title
Clinical and radiological anastomotic leak rate
Title
Progression-free survival and patterns of failure
Title
Overall survival
Title
Safety
Title
Quality of life, including long-term bowel function
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
David Cunningham, MD
Organizational Affiliation
Royal Marsden NHS Foundation Trust
Official's Role
Study Chair
Facility Information:
Facility Name
Vall d'Hebron University Hospital
City
Barcelona
ZIP/Postal Code
08035
Country
Spain
Facility Name
Hospital Universitario La Paz
City
Madrid
ZIP/Postal Code
28046
Country
Spain
Facility Name
Hospital Clinico Universitario de Valencia
City
Valencia
ZIP/Postal Code
46010
Country
Spain
Facility Name
Karolinska University Hospital - Solna
City
Stockholm
ZIP/Postal Code
S-171 76
Country
Sweden
Facility Name
Uppsala University Hospital
City
Uppsala
ZIP/Postal Code
S-75185
Country
Sweden
Facility Name
Royal Bournemouth Hospital NHS Trust
City
Bournemouth
State/Province
England
ZIP/Postal Code
BH7 7DW
Country
United Kingdom
Facility Name
Sussex Cancer Centre at Royal Sussex County Hospital
City
Brighton
State/Province
England
ZIP/Postal Code
BN2 5BE
Country
United Kingdom
Facility Name
Eastbourne District General Hospital
City
Eastbourne
State/Province
England
ZIP/Postal Code
BN21 2UD
Country
United Kingdom
Facility Name
Cancer Research UK Clinical Groups at Guy's King's & St. Thomas' Hospitals
City
London
State/Province
England
ZIP/Postal Code
SE5 9NU
Country
United Kingdom
Facility Name
Mid Kent Oncology Centre at Maidstone Hospital
City
Maidstone
State/Province
England
ZIP/Postal Code
ME16 9QQ
Country
United Kingdom
Facility Name
Dorset Cancer Centre
City
Poole Dorset
State/Province
England
ZIP/Postal Code
BH15 2JB
Country
United Kingdom
Facility Name
Southampton General Hospital
City
Southampton
State/Province
England
ZIP/Postal Code
SO16 6YD
Country
United Kingdom
Facility Name
Royal Marsden - Surrey
City
Sutton
State/Province
England
ZIP/Postal Code
SM2 5PT
Country
United Kingdom
12. IPD Sharing Statement
Learn more about this trial
Oxaliplatin, Capecitabine, and Radiation Therapy With or Without Cetuximab in Treating Patients Undergoing Surgery for High-Risk Rectal Cancer
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