Combination Chemotherapy and Cetuximab as First-Line Therapy in Treating Patients With Advanced and/or Metastatic Colorectal Cancer

Phase 2

Completed

• Conditions: Colorectal Cancer
• Interventions: Biological: cetuximab; Drug: capecitabine; Drug: fluorouracil; Drug: leucovorin calcium; Drug: oxaliplatin; Other: immunohistochemistry staining method; Other: laboratory biomarker analysis

• Registration Number: NCT00640081
• Lead Sponsor: Cheryl Pugh

Brief 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. 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.

Basic Information
|
Recruitment & Eligibility
|
Study & Design
|
Trial Locations

Study Timeline

• Study Start: 2007-07
• Study First Submitted: 2008-03-19
• Study First Submitted QC: 2008-03-19
• Study First Posted: 2008-03-20
• Primary Completion: 2010-06
• Study Completion: 2015-09
• Status Verified: 2021-09
• Last Update Submitted: 2021-09-15
• Last Update Posted: 2021-09-22

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 169

Inclusion Criteria

Not provided

Read More

Exclusion Criteria

Not provided

Read More

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
D	leucovorin calcium	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
E	immunohistochemistry staining method	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
D	laboratory biomarker analysis	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
E	cetuximab	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
E	laboratory biomarker analysis	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
D	immunohistochemistry staining method	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
D	cetuximab	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
E	leucovorin calcium	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
D	capecitabine	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
D	fluorouracil	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
D	oxaliplatin	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
E	fluorouracil	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
E	capecitabine	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
E	oxaliplatin	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

Primary Outcome Measures

Name	Time	Method
Failure-free survival at 10 months	10 months

Secondary Outcome Measures

Name	Time	Method
Overall survival	at 12, 24 and 36 weeks
Progression-free survival	at 12, 24 and 36 weeks
Toxicity of each treatment regimen by NCI CTCAE v3.0	at 12, 24 and 36 weeks
Safety of cetuximab reintroduction, in terms of risk of grade 3-4 allergic reactions	12, 24 and 36 weeks
Proportion of patients achieving disease control (complete response plus partial response plus stable disease) at 24 weeks	24 weeks
Response rates	at 12, 24 and 36 weeks

Trial Locations

Locations (25)

Weston Park; 🇬🇧 Sheffield, United Kingdom

Darent Valley Hospital; 🇬🇧 Dartford, United Kingdom

Guys and St Thomas' hospitals; 🇬🇧 London, United Kingdom

Dorset Cancer Centre, Poole Hospital; 🇬🇧 Poole, United Kingdom

Hereford County Hospital; 🇬🇧 Hereford, United Kingdom

Worcestershire Royal Hospital; 🇬🇧 Worcester, United Kingdom

Gloucestershire Oncology Centre at Cheltenham General Hospital; 🇬🇧 Cheltenham, England, United Kingdom

Bradford Royal Infirmary; 🇬🇧 Bradford, England, United Kingdom

Bank of Cyprus Oncology Centre; 🇨🇾 Nicosia, Cyprus

Dorset County Hospital; 🇬🇧 Dorchester, England, United Kingdom

St. Mary's Hospital; 🇬🇧 London, England, United Kingdom

Peterborough Hospitals Trust; 🇬🇧 Peterborough, England, United Kingdom

St. Luke's Cancer Centre at Royal Surrey County Hospital; 🇬🇧 Guildford, England, United Kingdom

Southport and Ormskirk; 🇬🇧 Southport, United Kingdom

Charing Cross Hospital; 🇬🇧 London, United Kingdom

Warrington and Halton Hospitals; 🇬🇧 Warrington, United Kingdom

Essex County Hospital; 🇬🇧 Colchester, England, United Kingdom

Hammersmith Hospital; 🇬🇧 London, England, United Kingdom

Churchill Hospital; 🇬🇧 Oxford, England, United Kingdom

University Hospital of North Staffordshire; 🇬🇧 Stoke-On-Trent, England, United Kingdom

Singleton Hospital; 🇬🇧 Swansea, Wales, United Kingdom

Royal Bournemouth Hospital; 🇬🇧 Bournemouth, United Kingdom

Royal United Hospital; 🇬🇧 Bath, United Kingdom

Addenbrookes Hospital; 🇬🇧 Cambridge, United Kingdom

St Helens and Whiston hospitals; 🇬🇧 St Helens, United Kingdom