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

NCT00268463 | Terminated Phase 3 Results DMC

• 2 other identifiers: NSABP C-09U10CA012027
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 31

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.

Conditions

Colorectal Cancer; Metastatic Cancer

Keywords

liver metastases; stage IV colon cancer; stage IV rectal cancer; adenocarcinoma of the colon; adenocarcinoma of the rectum

Outcome Measures

Primary Outcomes (1)

• Progression-free Interval (PFI)

  Time to first recurrence of colon cancer at any site

  Time from randomization through year 5

Secondary Outcomes (4)

• Liver PFI as Measured by Time to Hepatic Progression.

  Time from randomization through year 5

• Survival as Measured by Time to Death From Any Cause.

  Time from randomization through year 5

• 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

• 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

Study Arms (2)

Arm 1: Capecitabine + Oxaliplatin

ACTIVE COMPARATOR

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; Drug: oxaliplatin

Arm 2: Floxuridine + Oxaliplatin + Capecitabine

EXPERIMENTAL

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; Drug: floxuridine; Drug: oxaliplatin

Interventions

capecitabine DRUG

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

Also known as: Xeloda

Arm 1: Capecitabine + Oxaliplatin; Arm 2: Floxuridine + Oxaliplatin + Capecitabine

floxuridine DRUG

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

Also known as: FUDR

Arm 2: Floxuridine + Oxaliplatin + Capecitabine

oxaliplatin DRUG

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

Also known as: Eloxatin

Arm 1: Capecitabine + Oxaliplatin; Arm 2: Floxuridine + Oxaliplatin + Capecitabine

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• NSABP Foundation Inc: lead
• National Cancer Institute (NCI): collaborator

Study Sites (31)

Cancer Care Center at John Muir Health - Concord Campus

Concord, California, 94524-4110, United States

Location

City of Hope Comprehensive Cancer Center

Duarte, California, 91010-3000, United States

Location

Veterans Affairs Medical Center - Loma Linda (Pettis)

Loma Linda, California, 92357, United States

Location

Kaiser Permanente Medical Center - Walnut Creek

Walnut Creek, California, 94596, United States

Location

John Muir/Mt. Diablo Comprehensive Cancer Center

Walnut Creek, California, 94598, United States

Location

CCOP - Christiana Care Health Services

Newark, Delaware, 19713, United States

Location

Washington Cancer Institute at Washington Hospital Center

Washington D.C., District of Columbia, 20010, United States

Location

Curtis & Elizabeth Anderson Cancer Institute at Memorial Health University Medical Center

Savannah, Georgia, 31403-3089, United States

Location

Via Christi Cancer Center at Via Christi Regional Medical Center

Wichita, Kansas, 67214, United States

Location

Central Baptist Hospital

Lexington, Kentucky, 40503-9985, United States

Location

Louisville Oncology at Norton Cancer Center

Louisville, Kentucky, 40202, United States

Location

CCOP - Ochsner

New Orleans, Louisiana, 70121, United States

Location

Harry & Jeanette Weinberg Cancer Institute at Franklin Square Hospital Center

Baltimore, Maryland, 21237, United States

Location

Saint Joseph Mercy Cancer Center

Ann Arbor, Michigan, 48106-0995, United States

Location

Borgess Medical Center

Kalamazoo, Michigan, 49001, United States

Location

West Michigan Cancer Center

Kalamazoo, Michigan, 49007-3731, United States

Location

Bronson Methodist Hospital

Kalamazoo, Michigan, 49007, United States

Location

Mayo Clinic Cancer Center

Rochester, Minnesota, 55905, United States

Location

Wake Forest University Comprehensive Cancer Center

Winston-Salem, North Carolina, 27157-1096, United States

Location

Altru Cancer Center at Altru Hospital

Grand Forks, North Dakota, 58201, United States

Location

Natalie Warren Bryant Cancer Center at St. Francis Hospital

Tulsa, Oklahoma, 74136, United States

Location

Legacy Good Samaritan Hospital & Medical Center Comprehensive Cancer Center

Portland, Oregon, 97210, United States

Location

CCOP - Columbia River Oncology Program

Portland, Oregon, 97225, United States

Location

Providence St. Vincent Medical Center

Portland, Oregon, 97225, United States

Location

St. Luke's Cancer Network at St. Luke's Hospital

Bethlehem, Pennsylvania, 18015, United States

Location

Geisinger Medical Center

Danville, Pennsylvania, 17822-0001, United States

Location

UMC Southwest Cancer and Research Center

Lubbock, Texas, 79415-3364, United States

Location

Fletcher Allen Health Care - University Health Center Campus

Burlington, Vermont, 05401, United States

Location

Virginia Oncology Associates - Hampton

Hampton, Virginia, 23666, United States

Location

Mary Babb Randolph Cancer Center at West Virginia University Hospitals

Morgantown, West Virginia, 26506, United States

Location

University of Wisconsin Paul P. Carbone Comprehensive Cancer Center

Madison, Wisconsin, 53792-6164, United States

Location

MeSH Terms

Conditions

Colorectal Neoplasms; Neoplasm Metastasis; Colonic Neoplasms; Rectal Neoplasms

Interventions

Capecitabine; Floxuridine; Oxaliplatin

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Deoxyuridine; Uridine; Coordination Complexes; Organic Chemicals

Results Point of Contact

• Title: Director, Division of Regulatory Affairs
• Organization: NSABP Foundation, Inc.

412-330-4600

Study Officials

• Norman Wolmark, MD

  NSABP Foundation Inc

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 20, 2005
• First Posted: December 22, 2005
• Study Start: January 1, 2006
• Primary Completion: June 1, 2008
• Study Completion: June 1, 2008
• Last Updated: May 15, 2013
• Results First Posted: March 15, 2013

Record last verified: 2013-05

Locations

US (31)