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Oxaliplatin and Capecitabine With or Without an Hepatic Arterial Infusion With Floxuridine in Treating Patients Who Are Undergoing Surgery and/or Ablation for Liver Metastases Due to Colorectal Cancer

This study has been terminated.
(The study was terminated due to low accrual.)
Sponsor:
Collaborator:
Information provided by (Responsible Party):
NSABP Foundation Inc
ClinicalTrials.gov Identifier:
NCT00268463
First received: December 20, 2005
Last updated: May 10, 2013
Last verified: May 2013
  Purpose

RATIONALE: Drugs used in chemotherapy, such as oxaliplatin, capecitabine, and floxuridine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Hepatic arterial infusion uses a catheter to carry tumor-killing substances, such as chemotherapy, directly into the liver. Giving chemotherapy in different ways may kill more tumor cells. It is not yet known whether giving oxaliplatin and capecitabine together with an hepatic arterial infusion with floxuridine is more effective than giving oxaliplatin and capecitabine alone in treating patients who are undergoing surgery and/or ablation for liver metastases due to colorectal cancer.

PURPOSE: This randomized phase III trial is studying oxaliplatin, capecitabine, and an hepatic arterial infusion with floxuridine to see how well they work compared to oxaliplatin and capecitabine in treating patients who are undergoing surgery and/or ablation for liver metastases due to colorectal cancer.


Condition Intervention Phase
Colorectal Cancer
Metastatic Cancer
Drug: capecitabine
Drug: floxuridine
Drug: oxaliplatin
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by NSABP Foundation Inc:

Primary Outcome Measures:
  • Progression-free Interval (PFI) [ Time Frame: Time from randomization through year 5 ] [ Designated as safety issue: No ]
    Time to first recurrence of colon cancer at any site


Secondary Outcome Measures:
  • Liver PFI as Measured by Time to Hepatic Progression. [ Time Frame: Time from randomization through year 5 ] [ Designated as safety issue: No ]
  • Survival as Measured by Time to Death From Any Cause. [ Time Frame: Time from randomization through year 5 ] [ Designated as safety issue: No ]
  • Scales Specific to Social/Family, Emotional, and Functional Well-being, Perceived Convenience of Care, and Self-reported Symptoms [ Time Frame: Prior to randomization, 4-6 weeks after surgery, 18 weeks after starting chemotherapy and after completion of chemotherapy ] [ Designated as safety issue: No ]
  • Quality of Life as Measured by the Functional Assessment of Cancer Therapy Trial Outcome Index at Baseline, at 4-6 Weeks Following Surgery (Before Initiation of Chemotherapy), and Periodically During Study [ Time Frame: Prior to randomization, 4-6 weeks after surgery, 18 weeks after the start of chemotherapy and after completion of chemotherapy ] [ Designated as safety issue: No ]

Enrollment: 22
Study Start Date: January 2006
Study Completion Date: June 2008
Primary Completion Date: June 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Arm 1: Capecitabine + Oxaliplatin
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 cycles in the absence of disease progression or unacceptable toxicity.
Drug: capecitabine

Oral capecitabine 850 mg/m2 twice daily on days 1-14 every 21 days for 8 cycles: Arm 1

Oral capecitabine 850 mg/m2 twice daily on days 22-35 every 42 days for 4 cycles and then on days 1-14 every 21 days for 4 cycles: Arm 2

Other Name: Xeloda
Drug: oxaliplatin

Oxaliplatin 130 mg/m2 IV over 2 hours on day 1 every 21 days for 8 cycles: Arm 1

Oxaliplatin 130 mg/m2 IV over 2 hours on day 22 every 42 days for 4 cycles and then on day 1 every 21 days for 4 cycles: Arm 2

Other Name: Eloxatin
Experimental: Arm 2: Floxuridine + Oxaliplatin + Capecitabine
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 cycles in the absence of unacceptable toxicity. Beginning with cycle 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 cycles.
Drug: capecitabine

Oral capecitabine 850 mg/m2 twice daily on days 1-14 every 21 days for 8 cycles: Arm 1

Oral capecitabine 850 mg/m2 twice daily on days 22-35 every 42 days for 4 cycles and then on days 1-14 every 21 days for 4 cycles: Arm 2

Other Name: Xeloda
Drug: floxuridine
Continuous hepatic arterial infusion of floxuridine 0.2 mg/kg on days 1-14 every 42 days for 4 cycles
Other Name: FUDR
Drug: oxaliplatin

Oxaliplatin 130 mg/m2 IV over 2 hours on day 1 every 21 days for 8 cycles: Arm 1

Oxaliplatin 130 mg/m2 IV over 2 hours on day 22 every 42 days for 4 cycles and then on day 1 every 21 days for 4 cycles: Arm 2

Other Name: Eloxatin

Detailed Description:

OBJECTIVES:

Primary

  • 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.

Secondary

  • 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.

Tertiary

  • Examine the prognostic worth, in terms of PFI, of specific molecular markers in hepatic metastases.

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 chemotherapy.

After completion of study treatment, patients are followed periodically.

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

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • 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 ablated
    • 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 randomization
  • No evidence of extrahepatic metastases
  • No prior colorectal metastases
  • No recurrent colorectal cancer concurrent with hepatic metastases

PATIENT CHARACTERISTICS:

  • 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 CONCURRENT THERAPY:

  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00268463

  Show 31 Study Locations
Sponsors and Collaborators
NSABP Foundation Inc
Investigators
Principal Investigator: Norman Wolmark, MD NSABP Foundation Inc
  More Information

Additional Information:
No publications provided

Responsible Party: NSABP Foundation Inc
ClinicalTrials.gov Identifier: NCT00268463     History of Changes
Other Study ID Numbers: NSABP C-09, U10CA012027
Study First Received: December 20, 2005
Results First Received: February 5, 2013
Last Updated: May 10, 2013
Health Authority: United States: Federal Government

Keywords provided by NSABP Foundation Inc:
liver metastases
stage IV colon cancer
stage IV rectal cancer
adenocarcinoma of the colon
adenocarcinoma of the rectum

Additional relevant MeSH terms:
Colorectal Neoplasms
Neoplasm Metastasis
Colonic Diseases
Digestive System Diseases
Digestive System Neoplasms
Gastrointestinal Diseases
Gastrointestinal Neoplasms
Intestinal Diseases
Intestinal Neoplasms
Neoplasms
Neoplasms by Site
Neoplastic Processes
Pathologic Processes
Rectal Diseases
Capecitabine
Floxuridine
Fluorouracil
Oxaliplatin
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on November 25, 2014