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A Phase III Clinical Trial Comparing Oxaliplatin, Capecitabine and Hepatic Arterial Infusion of Floxuridine to Oxaliplatin and Capecitabine in Patients With Resected or Ablated Liver Metastases From Colorectal Cancer

Phase 3
18 Years
Not Enrolling
Colorectal Cancer, Metastatic Cancer

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Trial Information

A Phase III Clinical Trial Comparing Oxaliplatin, Capecitabine and Hepatic Arterial Infusion of Floxuridine to Oxaliplatin and Capecitabine in Patients With Resected or Ablated Liver Metastases From Colorectal Cancer



- Compare progression-free interval (PFI) in patients undergoing surgical resection
and/or ablation for hepatic metastases from colorectal cancer treated with adjuvant
therapy comprising oxaliplatin and capecitabine with vs without hepatic arterial
infusion of floxuridine.


- Compare overall survival and liver PFI between the two treatment groups.

- Assess toxicity in each of the treatment regimens.

- Compare self-reported symptoms between two treatment groups.

- Compare quality of life in each of the treatment regimens.


- Examine the prognostic worth, in terms of PFI, of specific molecular markers in hepatic

OUTLINE: This is a randomized study. Patients are stratified according to intended surgical
technique (surgical resection alone vs cryoablation or radiofrequency ablation [RFA] alone
vs combination of resection and ablation) and prior adjuvant chemotherapy regimen
(chemotherapy with vs without oxaliplatin vs no chemotherapy). Patients are randomized to 1
of 2 treatment arms.

All patients undergo surgical resection and/or hepatic cryoablation or RFA to remove a
maximum of 6 colorectal hepatic metastases. Patients randomized to arm II also undergo
intra-arterial catheter and if applicable, pump placement.

- Arm 1 (oxaliplatin and capecitabine): Within 4-6 weeks after surgery and/or ablation,
patients receive oxaliplatin IV over 2 hours on day 1 and oral capecitabine twice daily
on days 1-14. Treatment repeats every 21 days for 8 courses in the absence of disease
progression or unacceptable toxicity.

- Arm 2 (oxaliplatin, capecitabine, and hepatic arterial infusion of floxuridine): Within
4-6 weeks after surgery and/or ablation, patients receive a continuous hepatic arterial
infusion of floxuridine on days 1-14, oxaliplatin IV over 2 hours on day 22, and oral
capecitabine twice daily on days 22-35. Treatment repeats every 42 days for 4 courses
in the absence of unacceptable toxicity. Beginning with course 5, patients receive
oxaliplatin IV over 2 hours on day 1 and oral capecitabine twice daily on days 1-14.
Treatment with oxaliplatin and capecitabine repeats every 21 days for 4 courses in the
absence of disease progression or unacceptable toxicity.

Quality of life is assessed at baseline, 4-6 weeks after surgery or ablation, approximately
18 weeks after beginning of chemotherapy, and 4-6 weeks after beginning the last cycle of

After completion of study treatment, patients are followed periodically.

PROJECTED ACCRUAL: A total of 400 patients will be accrued for this study.

Inclusion Criteria


- Histologically* or cytologically confirmed colorectal adenocarcinoma

- No other cellular type (e.g., sarcoma, lymphoma, or carcinoid) NOTE: *If the
primary colorectal tumor and the hepatic lesions have been identified at the
same time and it is not possible to biopsy the colorectal lesion, the patient
will be eligible without histologic confirmation of the colorectal primary
cancer as long as other radiographic studies or scans document the
characteristics of a colorectal cancer

- Synchronous or metachronous metastatic disease confined to the liver

- No more than 6 hepatic metastatic lesions that can potentially be resected or

- For patients presenting with synchronous lesion(s) in the colon and/or rectum,
the primary tumors must, in the opinion of the investigator, appear to be
completely resectable

- Must be able to undergo surgery and/or ablation within 28 days following

- No evidence of extrahepatic metastases

- No prior colorectal metastases

- No recurrent colorectal cancer concurrent with hepatic metastases


- Life expectancy ≥ 5 years, excluding their colorectal cancer

- Eastern Cooperative Oncology Group (ECOG) (Zubrod) performance status 0-1

- No other malignancy within the past 5 years except carcinoma in situ of the cervix,
melanoma in situ, basal cell or squamous cell skin cancer, or carcinoma of the colon
or rectum

- Absolute granulocyte count ≥ 1,200/mm^3

- Platelet count ≥ 100,000/mm^3

- PT/international normalized ratio (INR) ≤ 1.5 unless patient is on therapeutic doses
of anticoagulant medication

- Total bilirubin ≤ upper limit of normal (ULN)

- Alkaline phosphatase ≤ 2.5 ULN

- aspartate aminotransferase (AST) ≤ 2.5 times ULN

- Calculated creatinine clearance > 50 mL/min

- Not pregnant or lactating

- Negative pregnancy test

- Patients with child bearing potential must agree to use adequate contraception

- Able to swallow oral medication

- No preexisting chronic hepatic disease (e.g., chronic active hepatitis or cirrhosis)

- No grade 3 or 4 anorexia or nausea

- No vomiting ≥ grade 2

- No clinically significant peripheral neuropathy defined as ≥ grade 2 neurosensory or
neuromotor toxicity

- No psychiatric or addictive disorders or other condition that, in the opinion of the
investigator, would preclude study participation


- Prior adjuvant fluorouracil alone or in combination with levamisole, leucovorin
calcium, irinotecan hydrochloride, or oxaliplatin allowed if these regimens were
completed > 6 months ago

- No prior resection/ablation, hepatic arterial infusion therapy, or any systemic
chemotherapy for metastatic disease

- Prior excisional biopsy allowed

- No prior radiotherapy to the liver

- No concurrent bevacizumab in patients who have had pump/catheter placement receiving
hepatic arterial infusion of floxuridine

- Patients who meet specific situations outlined in the protocol and who have not
had pump placement may receive bevacizumab at the physician's discretion

- No concurrent halogenated antiviral agents such as sorivudine or brivudine in
patients receiving fluorouracil, floxuridine, or capecitabine

- No concurrent filgrastim (G-CSF), pegfilgrastim, or sargramostim (GM-CSF) as primary
prophylaxis for neutropenia

- Following neutropenic events, these drugs may be used at the physician's
discretion during subsequent cycles

- No other concurrent cancer therapy

- No other concurrent investigational agents

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Progression-free Interval (PFI)

Outcome Description:

Time to first recurrence of colon cancer at any site

Outcome Time Frame:

Time from randomization through year 5

Safety Issue:


Principal Investigator

Norman Wolmark, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

NSABP Foundation, Inc.


United States: Federal Government

Study ID:




Start Date:

January 2006

Completion Date:

June 2008

Related Keywords:

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



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