Colorectal CancerPhase 2NCT00640081
Combination Chemotherapy and Cetuximab as First-Line Therapy in Treating Patients With Advanced and/or Metastatic Colorectal Cancer
A Phase 2 study testing cetuximab, capecitabine and fluorouracil in people with Colorectal Cancer, run by Cheryl Pugh at 25 sites in 2 countries.
Trial summary
RATIONALE: Drugs used in chemotherapy work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as cetuximab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Read more about this study
- Who is it for?
- Ages 18 to 100 years
- Conditions the study is for
- Colorectal Cancer
- What is being tested?
- cetuximab, capecitabine and fluorouracil
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 169 participants
- Where
- 25 sitesin 2 countries
- Study dates
- Jul 2007to Sep 2015
- 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 to 100 years
- All sexes
- No healthy volunteers
- Adult, Older adult
DISEASE CHARACTERISTICS:
- Diagnosis of colorectal adenocarcinoma, defined by 1 of the following:
- Prior or current histologically confirmed primary adenocarcinoma of colon or rectum with clinical or radiological evidence of advanced and/or metastatic disease
- Histologically and cytologically confirmed metastatic adenocarcinoma with clinical and/or radiological evidence of colorectal primary tumor
- Unidimensionally measurable disease by RECIST criteria
- Inoperable metastatic or locoregional disease
- Potentially resectable liver metastases allowed provided the following criteria are met:
- Fewer than 4 unilobar liver metastases, each < 4 cm in size and without major vascular involvement
- No combination chemotherapy allowed prior to the planned resection of operable liver metastases
- No confirmed K-ras mutation of tumor after screening
- No brain metastases
PATIENT CHARACTERISTICS:
- WHO performance status 0-2
- Must be considered fit to undergo combination chemotherapy
- ANC ≥ 1,500/mm³
- Platelet count ≥ 100,000/mm³
- Serum bilirubin ≤ 1.25 times upper limit of normal (ULN)
- Alkaline phosphatase ≤ 5 times ULN
- AST or ALT ≤ 2.5 times ULN
- Creatinine clearance ≥ 50mL/min OR glomerular filtration rate ≥ 50 mL/min
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- No severe uncontrolled concurrent medical illness (including poorly controlled angina or myocardial infarction within the past 12 weeks) likely to interfere with protocol treatments
- No psychiatric or neurological condition that would preclude study compliance with oral medication or giving informed consent
- No partial or complete bowel obstruction
- No preexisting neuropathy > grade 1
- No prior or current malignant disease which, in the judgement of the treating investigator, is likely to interfere with COIN-B treatment or assessment of response
- No patients with known hypersensitivity reactions to any of the components of the study treatments
- No proven dihydropyrimidine dehydrogenase deficiency (DPD) or personal or family history of DPD
PRIOR CONCURRENT THERAPY:
- See Disease Characteristics
- No prior systemic palliative chemotherapy for metastatic disease
- No prior oxaliplatin
- More than 1 month since prior adjuvant chemotherapy comprising fluorouracil (with or without leucovorin calcium), capecitabine, or irinotecan hydrochloride
- More than 1 month since prior chemoradiotherapy comprising fluorouracil (with or without leucovorin calcium) or capecitabine for rectal cancer
- No ongoing requirement for contraindicated concurrent medication
- No concurrent enrollment in any type of study other than observational studies
Trial locations and contacts
25 sites in 2 countries.
25 sites in 2 countries
United Kingdom24 sites
Royal United Hospital
Bath
Royal Bournemouth Hospital
Bournemouth
Bradford Royal Infirmary
Bradford, England, BD9 6RJ
Addenbrookes Hospital
Cambridge
Gloucestershire Oncology Centre at Cheltenham General Hospital
Cheltenham, England, GL53 7AN
Essex County Hospital
Colchester, England, C03 3NB
Darent Valley Hospital
Dartford
Dorset County Hospital
Dorchester, England, DT1 2JY
St. Luke's Cancer Centre at Royal Surrey County Hospital
Guildford, England, GU2 7XX
Hereford County Hospital
Hereford
Hammersmith Hospital
London, England, W12 OHS
St. Mary's Hospital
London, England, W2 1NY
Charing Cross Hospital
London
Guys and St Thomas' hospitals
London
Churchill Hospital
Oxford, England, OX3 7LJ
Peterborough Hospitals Trust
Peterborough, England, PE3 6DA
Dorset Cancer Centre, Poole Hospital
Poole
Weston Park
Sheffield, S10 2SJ
Southport and Ormskirk
Southport
St Helens and Whiston hospitals
St Helens
University Hospital of North Staffordshire
Stoke-on-Trent, England, ST4 7LN
Singleton Hospital
Swansea, Wales, SA2 8QA
Warrington and Halton Hospitals
Warrington
Worcestershire Royal Hospital
Worcester
About this study
Official title: A Two-arm Phase II Randomised Trial of Intermittent Chemotherapy Plus Continuous Cetuximab and of Intermittent Chemotherapy Plus Intermittent Cetuximab in First Line Treatment of Patients With K-ras-normal (Wild-type) Metastatic Colorectal Cancer
RATIONALE: Drugs used in chemotherapy work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. 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. It is not yet known whether giving combination chemotherapy together with intermittent cetuximab is more effective than combination chemotherapy given together with continuous cetuximab in treating colorectal cancer.
PURPOSE: This randomized phase II trial is studying giving combination chemotherapy together with intermittent cetuximab to see how well it works compared to combination chemotherapy given together with continuous cetuximab as first-line therapy in treating patients with advanced or metastatic colorectal cancer.
Read the detailed description
OBJECTIVES:
Primary
- To compare the activity, in terms of failure-free survival, of patients with K-ras-normal (wild type) advanced and/or metastatic colorectal cancer treated with intermittent combination chemotherapy comprising oxaliplatin, leucovorin calcium, and fluorouracil (OxMdG) or oxaliplatin and capecitabine (XELOX) and intermittent vs continuous cetuximab as first-line therapy.
- To compare the safety and feasibility of these regimens in these patients.
Secondary
- To compare the safety of cetuximab reintroduction, in terms of frequency of grade 3-4 allergic reactions in these patients.
- To compare improvement in disease control (i.e., complete response plus partial response plus stable disease) at 24 weeks in patients treated with these regimens.
- To compare overall and progression-free survival of patients treated with these regimens.
- To compare response rates at 12, 24, and 36 weeks in patients treated with these regimens.
- To compare toxicity of these regimens in these patients.
OUTLINE: This is a multicenter study. Patients are randomised to 1 of 2 treatment arms.
- Arm I (intermittent chemotherapy and intermittent cetuximab): Patients receive 1 of the following combination chemotherapy and cetuximab regimens:
- OxMdG: Patients receive oxaliplatin IV over 2 hours and leucovorin calcium IV over 2 hours on day 1 and fluorouracil IV continuously over 46 hours on days 1 and 2. Patients also receive cetuximab IV over 1-2 hours on days 1 and 8. Treatment repeats every 14 days for up to 6 courses (12 weeks) in the absence of disease progression or unacceptable toxicity.
- XELOX (for patients with line-related problems): Patients receive oxaliplatin IV over 2 hours on day 1 and oral capecitabine twice daily on days 1-15 (28 doses). Patients also receive cetuximab IV over 1-2 hours on days 1, 8, and 15. Treatment repeats every 21 days for up to 4 courses (12 weeks) in the absence of disease progression or unacceptable toxicity.
After completion of 12 weeks of study therapy, patients with disease progression are removed from study. Patients with stable or responding disease stop treatment with OxMdG or XELOX and cetuximab and undergo clinical evaluation at least every 6 weeks until disease progression or clinical deterioration. Upon evidence of disease progression or clinical deterioration, patients restart treatment with OxMdG or XELOX and cetuximab as before and continue to alternate 12 weeks of treatment with treatment breaks in the absence of disease progression or unacceptable toxicity. Patients with disease progression during study therapy stop treatment and proceed to second-line therapy or best supportive care.
- Arm II (intermittent chemotherapy and continuous cetuximab): Patients receive OxMdG or XELOX and cetuximab for 12 weeks as in arm I. Patients with disease progression after 12 weeks of study therapy are removed from study. Patients with stable or responding disease* after 12 weeks of study therapy stop treatment with OxMdG or XELOX and continue treatment with cetuximab weekly as monotherapy in the absence of disease progression or unacceptable toxicity. Patients undergo clinical evaluation as in arm I. Upon progression, patients restart treatment with OxMdG or XELOX and continue cetuximab, as before, alternating 12 weeks of combined OxMdG or XELOX and cetuximab therapy with cetuximab monotherapy. Patients with disease progression during study therapy stop treatment and proceed to second-line therapy as in arm I.
Previously collected tumor tissue samples are obtained at baseline and analyzed by IHC for EGFR status of tumor.
After completion of study treatment, patients are followed every 12 weeks.
Peer Reviewed and Funded or Endorsed by Cancer Research UK.
- Conditions
- Colorectal Cancer
- Being tested
- cetuximab, capecitabine, fluorouracil, leucovorin calcium, oxaliplatin
- Keywords
- adenocarcinoma of the colon, stage IV colon cancer, adenocarcinoma of the rectum, stage IV rectal cancer, stage III colon cancer, stage III rectal cancer, recurrent colon cancer, recurrent rectal cancer
- Medical subject headings
- Colorectal Neoplasms, Colonic Neoplasms, Rectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
cetuximabBiological
capecitabineDrug
fluorouracilDrug
oxaliplatinDrug
laboratory biomarker analysisOther
| Study group | Role | What they receive |
|---|---|---|
| D | Active comparator | Intermittent chemotherapy plus intermittent cetuximab treatment comprising 12 weeks of chemotherapy plus cetuximab followed by a period off all therapy, with reintroduction of the same chemotherapy and cetuximab regimen for a further 12 weeks after initial progression off treatment Receives: Biological: cetuximab; Drug: capecitabine; Drug: fluorouracil; Drug: leucovorin calcium; Drug: oxaliplatin; Other: immunohistochemistry staining method; Other: laboratory biomarker analysis |
| E | Experimental | Intermittent chemotherapy plus continuous cetuximab treatment comprising 12 weeks of chemotherapy plus cetuximab followed by a period of withdrawal of the chemotherapy, but continued weekly cetuximab monotherapy (maintenance cetuximab), with reintroduction of the same chemotherapy regimen to the cetuximab for a further 12 weeks after initial progression off chemotherapy treatment Receives: Biological: cetuximab; Drug: capecitabine; Drug: fluorouracil; Drug: leucovorin calcium; Drug: oxaliplatin; Other: immunohistochemistry staining method; Other: laboratory biomarker analysis |
What is being measured
The primary outcome is the main question the study is designed to answer.
Failure-free survival at 10 months
Measured: 10 months
Secondary outcomes (6)
Safety of cetuximab reintroduction, in terms of risk of grade 3-4 allergic reactions
Measured: 12, 24 and 36 weeks
Proportion of patients achieving disease control (complete response plus partial response plus stable disease) at 24 weeks
Measured: 24 weeks
Overall survival
Measured: at 12, 24 and 36 weeks
Progression-free survival
Measured: at 12, 24 and 36 weeks
Response rates
Measured: at 12, 24 and 36 weeks
Toxicity of each treatment regimen by NCI CTCAE v3.0
Measured: at 12, 24 and 36 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Mar 2008 (estimated)
- Study startJul 2007
- Primary completionJun 2010
- Study completionSep 2015
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.
- 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
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 169 participants (actual)
Sponsor and investigators
- Lead sponsor
- Cheryl Pugh
- Sponsor type
- Other government
- Responsible party
- Sponsor-investigator, Cheryl Pugh, Medical Research Council
- Investigators
- Harpreet S. Wasan, Principal investigator, Hammersmith Hospitals NHS Trust
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00640081
- Sponsor's protocol ID
- CDR0000589635
- Other IDs
- MRC-CTU-COIN-B/CR11, EUDRACT:2006-003049-17, ISRCTN38375681, EU-20828, MERCK-MRC-CTU-COIN-B/CR11
- Status last verified
- Sep 2021
- First submitted
- 19 Mar 2008
- Last updated
- 22 Sep 2021
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- Yes: Publication
Study at a glance
From the registry record, last updated by the sponsor on 22 Sep 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Two-arm Phase II Randomised Trial of Intermittent Chemotherapy Plus Continuous Cetuximab and of Intermittent Chemotherapy Plus Intermittent Cetuximab in First Line Treatment of Patients With K-ras-normal (Wild-type) Metastatic Colorectal Cancer
- ClinicalTrials.gov ID
- NCT00640081
- Acronym / sponsor ID
- CDR0000589635
- Conditions
- Colorectal Cancer
- Keywords
- adenocarcinoma of the colon, stage IV colon cancer, adenocarcinoma of the rectum, stage IV rectal cancer, stage III colon cancer, stage III rectal cancer, recurrent colon cancer, recurrent rectal cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 169 participants (actual)
- Lead sponsor
- Cheryl PughOther government
- Study start
- Jul 2007
- Primary completion
- Jun 2010 (actual)
- Study completion
- Sep 2015 (actual)
- First posted
- 20 Mar 2008 (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 work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. 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. It is not yet known whether giving combination chemotherapy together with intermittent cetuximab is more effective than combination chemotherapy given together with continuous cetuximab in treating colorectal cancer.
PURPOSE: This randomized phase II trial is studying giving combination chemotherapy together with intermittent cetuximab to see how well it works compared to combination chemotherapy given together with continuous cetuximab as first-line therapy in treating patients with advanced or metastatic colorectal cancer.
Detailed description
OBJECTIVES:
Primary
- To compare the activity, in terms of failure-free survival, of patients with K-ras-normal (wild type) advanced and/or metastatic colorectal cancer treated with intermittent combination chemotherapy comprising oxaliplatin, leucovorin calcium, and fluorouracil (OxMdG) or oxaliplatin and capecitabine (XELOX) and intermittent vs continuous cetuximab as first-line therapy.
- To compare the safety and feasibility of these regimens in these patients.
Secondary
- To compare the safety of cetuximab reintroduction, in terms of frequency of grade 3-4 allergic reactions in these patients.
- To compare improvement in disease control (i.e., complete response plus partial response plus stable disease) at 24 weeks in patients treated with these regimens.
- To compare overall and progression-free survival of patients treated with these regimens.
- To compare response rates at 12, 24, and 36 weeks in patients treated with these regimens.
- To compare toxicity of these regimens in these patients.
OUTLINE: This is a multicenter study. Patients are randomised to 1 of 2 treatment arms.
- Arm I (intermittent chemotherapy and intermittent cetuximab): Patients receive 1 of the following combination chemotherapy and cetuximab regimens:
- OxMdG: Patients receive oxaliplatin IV over 2 hours and leucovorin calcium IV over 2 hours on day 1 and fluorouracil IV continuously over 46 hours on days 1 and 2. Patients also receive cetuximab IV over 1-2 hours on days 1 and 8. Treatment repeats every 14 days for up to 6 courses (12 weeks) in the absence of disease progression or unacceptable toxicity.
- XELOX (for patients with line-related problems): Patients receive oxaliplatin IV over 2 hours on day 1 and oral capecitabine twice daily on days 1-15 (28 doses). Patients also receive cetuximab IV over 1-2 hours on days 1, 8, and 15. Treatment repeats every 21 days for up to 4 courses (12 weeks) in the absence of disease progression or unacceptable toxicity.
After completion of 12 weeks of study therapy, patients with disease progression are removed from study. Patients with stable or responding disease stop treatment with OxMdG or XELOX and cetuximab and undergo clinical evaluation at least every 6 weeks until disease progression or clinical deterioration. Upon evidence of disease progression or clinical deterioration, patients restart treatment with OxMdG or XELOX and cetuximab as before and continue to alternate 12 weeks of treatment with treatment breaks in the absence of disease progression or unacceptable toxicity. Patients with disease progression during study therapy stop treatment and proceed to second-line therapy or best supportive care.
- Arm II (intermittent chemotherapy and continuous cetuximab): Patients receive OxMdG or XELOX and cetuximab for 12 weeks as in arm I. Patients with disease progression after 12 weeks of study therapy are removed from study. Patients with stable or responding disease* after 12 weeks of study therapy stop treatment with OxMdG or XELOX and continue treatment with cetuximab weekly as monotherapy in the absence of disease progression or unacceptable toxicity. Patients undergo clinical evaluation as in arm I. Upon progression, patients restart treatment with OxMdG or XELOX and continue cetuximab, as before, alternating 12 weeks of combined OxMdG or XELOX and cetuximab therapy with cetuximab monotherapy. Patients with disease progression during study therapy stop treatment and proceed to second-line therapy as in arm I.
Previously collected tumor tissue samples are obtained at baseline and analyzed by IHC for EGFR status of tumor.
After completion of study treatment, patients are followed every 12 weeks.
Peer Reviewed and Funded or Endorsed by Cancer Research UK.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| D | Active comparator | Biological: cetuximab, Drug: capecitabine, Drug: fluorouracil, Drug: leucovorin calcium, Drug: oxaliplatin, Other: immunohistochemistry staining method, Other: laboratory biomarker analysisIntermittent chemotherapy plus intermittent cetuximab treatment comprising 12 weeks of chemotherapy plus cetuximab followed by a period off all therapy, with reintroduction of the same chemotherapy and cetuximab regimen for a further 12 weeks after initial progression off treatment |
| E | Experimental | Biological: cetuximab, Drug: capecitabine, Drug: fluorouracil, Drug: leucovorin calcium, Drug: oxaliplatin, Other: immunohistochemistry staining method, Other: laboratory biomarker analysisIntermittent chemotherapy plus continuous cetuximab treatment comprising 12 weeks of chemotherapy plus cetuximab followed by a period of withdrawal of the chemotherapy, but continued weekly cetuximab monotherapy (maintenance cetuximab), with reintroduction of the same chemotherapy regimen to the cetuximab for a further 12 weeks after initial progression off chemotherapy treatment |
Who may qualify
- Ages
- 18 to 100 years
- 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 | D, E |
| capecitabine | Drug | D, E |
| fluorouracil | Drug | D, E |
| leucovorin calcium | Drug | D, E |
| oxaliplatin | Drug | D, E |
| immunohistochemistry staining method | Other | D, E |
| laboratory biomarker analysis | Other | D, E |
Primary outcome
Failure-free survival at 10 months
Time frame: 10 months
6 secondary outcomes
Safety of cetuximab reintroduction, in terms of risk of grade 3-4 allergic reactions
Time frame: 12, 24 and 36 weeks
Proportion of patients achieving disease control (complete response plus partial response plus stable disease) at 24 weeks
Time frame: 24 weeks
Overall survival
Time frame: at 12, 24 and 36 weeks
Progression-free survival
Time frame: at 12, 24 and 36 weeks
Response rates
Time frame: at 12, 24 and 36 weeks
Toxicity of each treatment regimen by NCI CTCAE v3.0
Time frame: at 12, 24 and 36 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Sep 2021.
- Trial Summary on Sponsor's Website with trial citationsLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. Publication
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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.
Harpreet S. Wasan principal investigator
Hammersmith Hospitals NHS Trust
25 sites in 2 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 fluorouracil in people with Colorectal Cancer, run by Cheryl Pugh at 25 sites in 2 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: finished, as of the sponsor's last update on 22 Sep 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 25 sites in United Kingdom, Cyprus. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Failure-free survival at 10 months (time frame: 10 months). 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 22 Sep 2021.