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

Colorectal Cancer Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00268463
• Other study ID #: NSABP C-09
• Secondary ID: U10CA012027
• Status: Terminated
• Phase: Phase 3
• First received: December 20, 2005
• Last updated: May 10, 2013
• Start date: January 2006
• Est. completion date: June 2008

Study information

• Verified date: May 2013
• Source: NSABP Foundation Inc
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 22
• Est. completion date: June 2008
• Est. primary completion date: June 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

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

Related Conditions & MeSH terms

• Colorectal Cancer
• Colorectal Neoplasms
• Metastatic Cancer
• Neoplasm Metastasis

Intervention

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
• floxuridine
Continuous hepatic arterial infusion of floxuridine 0.2 mg/kg on days 1-14 every 42 days for 4 cycles
• 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

Locations

Country	Name	City	State
United States	Saint Joseph Mercy Cancer Center	Ann Arbor	Michigan
United States	Harry & Jeanette Weinberg Cancer Institute at Franklin Square Hospital Center	Baltimore	Maryland
United States	St. Luke's Cancer Network at St. Luke's Hospital	Bethlehem	Pennsylvania
United States	Fletcher Allen Health Care - University Health Center Campus	Burlington	Vermont
United States	Cancer Care Center at John Muir Health - Concord Campus	Concord	California
United States	Geisinger Medical Center	Danville	Pennsylvania
United States	City of Hope Comprehensive Cancer Center	Duarte	California
United States	Altru Cancer Center at Altru Hospital	Grand Forks	North Dakota
United States	Virginia Oncology Associates - Hampton	Hampton	Virginia
United States	Borgess Medical Center	Kalamazoo	Michigan
United States	Bronson Methodist Hospital	Kalamazoo	Michigan
United States	West Michigan Cancer Center	Kalamazoo	Michigan
United States	Central Baptist Hospital	Lexington	Kentucky
United States	Veterans Affairs Medical Center - Loma Linda (Pettis)	Loma Linda	California
United States	Louisville Oncology at Norton Cancer Center	Louisville	Kentucky
United States	UMC Southwest Cancer and Research Center	Lubbock	Texas
United States	University of Wisconsin Paul P. Carbone Comprehensive Cancer Center	Madison	Wisconsin
United States	Mary Babb Randolph Cancer Center at West Virginia University Hospitals	Morgantown	West Virginia
United States	CCOP - Ochsner	New Orleans	Louisiana
United States	CCOP - Christiana Care Health Services	Newark	Delaware
United States	CCOP - Columbia River Oncology Program	Portland	Oregon
United States	Legacy Good Samaritan Hospital & Medical Center Comprehensive Cancer Center	Portland	Oregon
United States	Providence St. Vincent Medical Center	Portland	Oregon
United States	Mayo Clinic Cancer Center	Rochester	Minnesota
United States	Curtis & Elizabeth Anderson Cancer Institute at Memorial Health University Medical Center	Savannah	Georgia
United States	Natalie Warren Bryant Cancer Center at St. Francis Hospital	Tulsa	Oklahoma
United States	John Muir/Mt. Diablo Comprehensive Cancer Center	Walnut Creek	California
United States	Kaiser Permanente Medical Center - Walnut Creek	Walnut Creek	California
United States	Washington Cancer Institute at Washington Hospital Center	Washington	District of Columbia
United States	Via Christi Cancer Center at Via Christi Regional Medical Center	Wichita	Kansas
United States	Wake Forest University Comprehensive Cancer Center	Winston-Salem	North Carolina

Sponsors (2)

Lead Sponsor	Collaborator
NSABP Foundation Inc	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-free Interval (PFI)	Time to first recurrence of colon cancer at any site	Time from randomization through year 5	No
Secondary	Liver PFI as Measured by Time to Hepatic Progression.		Time from randomization through year 5	No
Secondary	Survival as Measured by Time to Death From Any Cause.		Time from randomization through year 5	No
Secondary	Scales Specific to Social/Family, Emotional, and Functional Well-being, Perceived Convenience of Care, and Self-reported Symptoms		Prior to randomization, 4-6 weeks after surgery, 18 weeks after starting chemotherapy and after completion of chemotherapy	No
Secondary	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		Prior to randomization, 4-6 weeks after surgery, 18 weeks after the start of chemotherapy and after completion of chemotherapy	No