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A Prospective Randomised Open Label Trial of Oxaliplatin/Fluoropyrimidine Versus Oxaliplatin/Fluoropyrimidine Plus Cetuximab Pre and Post Operatively in Patients With Resectable Colorectal Liver Metastasis Requiring Chemotherapy


Phase 3
18 Years
N/A
Open (Enrolling)
Both
Colorectal Cancer, Metastatic Cancer

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Trial Information

A Prospective Randomised Open Label Trial of Oxaliplatin/Fluoropyrimidine Versus Oxaliplatin/Fluoropyrimidine Plus Cetuximab Pre and Post Operatively in Patients With Resectable Colorectal Liver Metastasis Requiring Chemotherapy


OBJECTIVES:

Primary

- Compare progression-free survival of patients with resectable colorectal liver
metastases treated with neoadjuvant and adjuvant combination chemotherapy with vs
without cetuximab.

Secondary

- Compare the overall survival of patients treated with these regimens.

- Compare the quality of life of patients treated with these regimens.

- Compare the cost effectiveness of these regimens in these patients.

OUTLINE: This is a prospective, randomized, multicenter, open-label study. Patients are
stratified according to participating center and assigned chemotherapy regimen. Patients are
randomized to 1 of 2 treatment arms.

- Neoadjuvant therapy:

- Arm I: Patients receive 1 of the following chemotherapy regimens:

- OxMdG: Patients receive leucovorin calcium IV over 2 hours and oxaliplatin IV
over 2 hours on day 1. Patients also receive fluorouracil IV continuously
over 46 hours beginning on day 1. Treatment repeats every 2 weeks for up to 6
courses in the absence of disease progression or unacceptable toxicity.

- CAPOX: Patients receive oxaliplatin IV over 2 hours on day 1 and oral
capecitabine twice daily on days 1-14. Treatment repeats every 3 weeks for up
to 4 courses in the absence of disease progression or unacceptable toxicity.

- Arm II: Patients receive 1 of the following regimens:

- OxMdG + cetuximab: Patients receive cetuximab IV over 1-2 hours on day 1 and
OxMdG chemotherapy as in arm I. Treatment repeats every 2 weeks for up to 6
courses in the absence of disease progression or unacceptable toxicity.

- CAPOX + cetuximab: Patients receive cetuximab IV over 1-2 hours on days 1, 8,
and 15 and CAPOX chemotherapy as in arm I. Treatment repeats every 3 weeks
for up to 4 courses in the absence of disease progression or unacceptable
toxicity.

- Surgery: Beginning 2-6 weeks after completion of chemotherapy, patients in both arms
undergo liver resection.

- Adjuvant therapy: Beginning 4-8 weeks after completion of surgery, patients receive
treatment (OxMdG or CAPOX with or without cetuximab) as in arm I or II of neoadjuvant
therapy.

- Arm I: Treatment with OxMdG repeats every 2 weeks for up to 6 courses and
treatment with CAPOX repeats every 3 weeks for up to 4 courses in the absence of
disease progression or unacceptable toxicity.

- Arm II: Treatment with OxMdG + cetuximab repeats every 2 weeks for up to 6 courses
and treatment with CAPOX + cetuximab repeats every 3 weeks for up to 4 courses in
the absence of disease progression or unacceptable toxicity.

Quality of life is assessed at baseline, every 12 weeks during chemotherapy, at completion
of study treatment, every 3 months for 1 year, and then every 6 months thereafter.

Cost per life year and per quality-adjusted life year is assessed at baseline, every 12
weeks during treatment, and then at 3, 5, and 10 years.

After completion of study treatment, patients are followed every 3 months for 2 years and
then every 6 months for 3 years.

Peer Reviewed and Funded or Endorsed by Cancer Research UK

Inclusion Criteria


DISEASE CHARACTERISTICS:

- Histologically* or radiologically confirmed primary adenocarcinoma of the colon or
rectum

- Advanced and/or metastatic disease NOTE: *Liver metastases should not be
biopsied

- Must have potentially resectable liver metastases present, as defined by any of the
following:

- Metachronous metastases AND complete resection of the primary tumor without
gross or microscopic evidence of residual disease (R0)

- Synchronous metastases AND R0 resection of the primary tumor > 1 month before
study entry

- Synchronous metastases with sufficient evidence (e.g., by CT scan or diagnostic
laparoscopy) that both the primary tumor and the liver metastases can be
completely resected during the same procedure and resection of primary tumor can
be delayed for 3-4 months

- Suboptimally resectable disease (i.e., potentially resectable disease with
compromise of the resection margins)

- No detectable extrahepatic tumor that cannot be completely resected

- Unidimensionally measurable disease

- No brain metastases

PATIENT CHARACTERISTICS:

- WHO performance status 0-2

- WBC ≥ 4,000/mm³

- ANC ≥ 1,500/mm³

- Platelet count > 150,000/mm³

- Bilirubin ≤ 1.25 times upper limit of normal (ULN)

- Alkaline phosphatase ≤ 5 times ULN

- AST or ALT ≤ 3 times ULN

- Creatinine clearance > 50 mL/min OR glomerular filtration rate > 50 mL/min

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception during and for ≥ 3 months after
completion of study treatment

- No psychiatric or neurological condition that would preclude study compliance

- No partial or complete bowel obstruction

- No preexisting neuropathy > grade 1

- No other prior or concurrent malignant disease that, in the opinion of the
investigator, would preclude study treatment

- No concurrent severe uncontrolled medical illness (including poorly-controlled angina
or myocardial infarction within the past 3 months) that would preclude study
treatment

- No known hypersensitivity reaction to any of the components of the study drugs

PRIOR CONCURRENT THERAPY:

- No prior systemic chemotherapy for metastatic disease

- More than 6 months since prior adjuvant chemotherapy comprising fluorouracil,
leucovorin calcium, capecitabine, or irinotecan hydrochloride

- More than 1 month since prior rectal chemoradiotherapy comprising fluorouracil and
leucovorin calcium

- No concurrent contraindicated medication

Type of Study:

Interventional

Study Design:

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Progression-free survival

Outcome Time Frame:

end of study

Safety Issue:

No

Principal Investigator

John N. Primrose, MD

Investigator Role:

Study Chair

Investigator Affiliation:

University Hospital Southampton NHS Foundation Trust.

Authority:

UK: Medicines and Healthcare producets Regulatory Agency

Study ID:

CDR0000549541

NCT ID:

NCT00482222

Start Date:

February 2007

Completion Date:

Related Keywords:

  • Colorectal Cancer
  • Metastatic Cancer
  • adenocarcinoma of the colon
  • stage IV colon cancer
  • adenocarcinoma of the rectum
  • stage IV rectal cancer
  • liver metastases
  • recurrent colon cancer
  • recurrent rectal cancer
  • Colorectal Neoplasms
  • Neoplasm Metastasis
  • Neoplasms
  • Neoplasms, Second Primary
  • Liver Neoplasms

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