Clinical trial NCT00268463: 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
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Colorectal Cancer
Metastatic Cancer
Keywords: liver metastases
stage IV colon cancer
stage IV rectal cancer
adenocarcinoma of the colon
adenocarcinoma of the rectum
Lead sponsor: NSABP Foundation Inc
Sponsor class: NETWORK
Collaborators: name: National Cancer Institute (NCI)
First posted: 2005-12-22
Enrollment: 22
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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 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

Primary outcomes:
measure: Progression-free Interval (PFI)
timeFrame: Time from randomization through year 5
Secondary outcomes:
measure: Liver PFI as Measured by Time to Hepatic Progression.
timeFrame: Time from randomization through year 5
measure: Survival as Measured by Time to Death From Any Cause.
timeFrame: Time from randomization through year 5
measure: Scales Specific to Social/Family, Emotional, and Functional Well-being, Perceived Convenience of Care, and Self-reported Symptoms
timeFrame: Prior to randomization, 4-6 weeks after surgery, 18 weeks after starting chemotherapy and after completion of chemotherapy
measure: 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
timeFrame: Prior to randomization, 4-6 weeks after surgery, 18 weeks after the start of chemotherapy and after completion of chemotherapy
Other outcomes:
Locations:
city: Concord
country: United States
facility: Cancer Care Center at John Muir Health - Concord Campus
state: California
city: Duarte
country: United States
facility: City of Hope Comprehensive Cancer Center
state: California
city: Loma Linda
country: United States
facility: Veterans Affairs Medical Center - Loma Linda (Pettis)
state: California
city: Walnut Creek
country: United States
facility: Kaiser Permanente Medical Center - Walnut Creek
state: California
city: Walnut Creek
country: United States
facility: John Muir/Mt. Diablo Comprehensive Cancer Center
state: California
city: Newark
country: United States
facility: CCOP - Christiana Care Health Services
state: Delaware
city: Washington
country: United States
facility: Washington Cancer Institute at Washington Hospital Center
state: District of Columbia
city: Savannah
country: United States
facility: Curtis & Elizabeth Anderson Cancer Institute at Memorial Health University Medical Center
state: Georgia
city: Wichita
country: United States
facility: Via Christi Cancer Center at Via Christi Regional Medical Center
state: Kansas
city: Lexington
country: United States
facility: Central Baptist Hospital
state: Kentucky
city: Louisville
country: United States
facility: Louisville Oncology at Norton Cancer Center
state: Kentucky
city: New Orleans
country: United States
facility: CCOP - Ochsner
state: Louisiana
city: Baltimore
country: United States
facility: Harry & Jeanette Weinberg Cancer Institute at Franklin Square Hospital Center
state: Maryland
city: Ann Arbor
country: United States
facility: Saint Joseph Mercy Cancer Center
state: Michigan
city: Kalamazoo
country: United States
facility: Borgess Medical Center
state: Michigan
city: Kalamazoo
country: United States
facility: West Michigan Cancer Center
state: Michigan
city: Kalamazoo
country: United States
facility: Bronson Methodist Hospital
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic Cancer Center
state: Minnesota
city: Winston-Salem
country: United States
facility: Wake Forest University Comprehensive Cancer Center
state: North Carolina
city: Grand Forks
country: United States
facility: Altru Cancer Center at Altru Hospital
state: North Dakota
city: Tulsa
country: United States
facility: Natalie Warren Bryant Cancer Center at St. Francis Hospital
state: Oklahoma
city: Portland
country: United States
facility: Legacy Good Samaritan Hospital & Medical Center Comprehensive Cancer Center
state: Oregon
city: Portland
country: United States
facility: CCOP - Columbia River Oncology Program
state: Oregon
city: Portland
country: United States
facility: Providence St. Vincent Medical Center
state: Oregon
city: Bethlehem
country: United States
facility: St. Luke's Cancer Network at St. Luke's Hospital
state: Pennsylvania
city: Danville
country: United States
facility: Geisinger Medical Center
state: Pennsylvania
city: Lubbock
country: United States
facility: UMC Southwest Cancer and Research Center
state: Texas
city: Burlington
country: United States
facility: Fletcher Allen Health Care - University Health Center Campus
state: Vermont
city: Hampton
country: United States
facility: Virginia Oncology Associates - Hampton
state: Virginia
city: Morgantown
country: United States
facility: Mary Babb Randolph Cancer Center at West Virginia University Hospitals
state: West Virginia
city: Madison
country: United States
facility: University of Wisconsin Paul P. Carbone Comprehensive Cancer Center
state: Wisconsin
Study officials:
affiliation: NSABP Foundation Inc
name: Norman Wolmark, MD
role: PRINCIPAL_INVESTIGATOR
References: