Hepatic Arterial Infusion Plus Chemotherapy in Treating Patients With Colorectal Cancer Metastatic to the Liver

Liver Metastases Clinical Trial

Official title:

A Phase II Trial Evaluating Multiple Metastasectomy Combined With Hepatic Artery Infusion Of Floxuridine (FUDR) And Dexamethasone (DXM), Alternating With Systemic Oxaliplatin (OXAL) And Capecitabine (CAPCIT) For Colorectal Carcinoma Metastatic To The Liver

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00026234
• Other study ID #: NCI-2012-01866
• Secondary ID: N9945CDR00000690
• Status: Completed
• Phase: Phase 2
• First received: November 9, 2001
• Last updated: July 15, 2013
• Start date: February 2002

Study information

• Verified date: June 2013
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

Phase II trial to study the effectiveness of hepatic arterial infusion plus chemotherapy in treating patients who have colorectal cancer metastatic to the liver. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Giving the drugs in different combinations and different ways may kill more tumor cells.

Description:

OBJECTIVES:

I. Determine the safety and toxicity of hepatic arterial infusion with floxuridine and dexamethasone followed by systemic therapy with oxaliplatin and capecitabine in patients with surgically resected liver metastases from primary colorectal carcinoma.

II. Determine the 2-year survival rate of patients treated with this regimen. III. Determine the 2-year recurrence rate and time to recurrence in patients treated with this regimen.

OUTLINE: This is a multicenter study.

Patients receive floxuridine and dexamethasone intra-arterially continuously on days 1-14, oxaliplatin IV over 2 hours on day 22, and oral capecitabine twice daily on days 22-35. Treatment repeats every 6 weeks for 4 courses in the absence of disease recurrence or unacceptable toxicity. After completion of the fourth course, patients receive oxaliplatin IV over 2 hours on day 1 and oral capecitabine twice daily on days 1-14. Treatment repeats every 3 weeks for 2 courses in the absence of disease recurrence or unacceptable toxicity.

Patients are followed every 3 months for 1 year and then every 6 months for 2.5 years.

PROJECTED ACCRUAL: A total of 15-75 patients will be accrued for this study within 9 months-3.25 years.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 75
• Est. primary completion date: January 2006
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A and older

Eligibility

Inclusion Criteria:

• Histologically confirmed colorectal adenocarcinoma metastatic to the liver

• No extrahepatic metastases

• Prior complete surgical resection of hepatic metastases (at least 1 lesion) within the past 21-56 days

• Negative surgical margins unless surrounding normal liver tissue was ablated during surgery

• Radiofrequency ablation may be used as adjunct to surgical resection but not as primary treatment

• No prior operative ultrasound during resection of hepatic metastases

• Prior complete surgical resection of carcinoma of colon or rectum (must appear completely resectable in case of synchronous lesions)

• Performance status - ECOG 0-1

• Absolute neutrophil count at least 1,200/mm^3

• Platelet count at least 100,000/mm^3

• Bilirubin no greater than 1.5 times upper limit of normal (ULN)

• AST no greater than 2.5 times ULN

• Alkaline phosphatase no greater than 2.5 times ULN

• No pre-existing chronic hepatic disease (chronic active hepatitis or cirrhosis)

• Creatinine no greater than ULN

• Creatinine clearance greater than 60 mL/min

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception

• Adequate oral nutrition (at least 1,500 calories/day)

• Able to withstand major operative procedure

• No dehydration

• No severe anorexia

• No frequent nausea or vomiting

• No prior or concurrent malignancy within the past 5 years except basal cell or squamous cell skin cancer or carcinoma in situ of any organ

• No prior or concurrent malignancy associated with more than 10% probability of death from malignant disease within 5 years of diagnosis

• No concurrent immunotherapy

• No concurrent colony-stimulating factors during the first course of study therapy

• No more than 1 prior adjuvant systemic fluorouracil (5-FU) regimen with or without levamisole, leucovorin calcium, or irinotecan

• One prior 5-FU-based regimen as neoadjuvant treatment for rectal cancer is allowed

• No prior hepatic artery infusion therapy with 5-FU or floxuridine

• No prior systemic chemotherapy for metastatic disease

• No other concurrent chemotherapy

• No concurrent radiotherapy

• See Disease Characteristics

• No prior or concurrent sorivudine or brivudine

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Adenocarcinoma
• Adenocarcinoma of the Colon
• Adenocarcinoma of the Rectum
• Liver Metastases
• Rectal Neoplasms
• Recurrent Colon Cancer
• Recurrent Rectal Cancer
• Stage IV Colon Cancer
• Stage IV Rectal Cancer

Intervention

Drug:
• floxuridine
Given intra-arterially
• dexamethasone
Given intra-arterially
• oxaliplatin
Given IV
• capecitabine
Given orally

Locations

Country	Name	City	State
United States	North Central Cancer Treatment Group	Rochester	Minnesota

Sponsors (2)

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

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Toxicity of oxaliplatin as assessed by the National Cancer Institute (NCI) Common Terminology Criteria (CTC) version 2.0		Up to 6 months	Yes
Primary	Survival rate		From the date of resection, cryoablation, or radiofrequency ablation to up to 2 years	No
Secondary	Survival time	The distribution of survival time will be estimated using the method of Kaplan-Meier.	Time from metastasectomy, cryoablation, or radiofrequency ablation to death due to any cause, assessed up to 3.5 years	No
Secondary	Time to recurrence	The distribution of the disease free interval will be estimated using the method of Kaplan-Meier.	Time from metastasectomy, cryoablation, or radiofrequency ablation to documentation of disease recurrence, assessed up to 2 years	No
Secondary	Time to treatment failure		From the date of metastasectomy, cryoablation, radiofrequency ablation to the date at which the patient is removed from treatment due to recurrence, toxicity, or refusal, assessed up to 3.5 years	No
Secondary	Adverse events as assessed by NCI CTC version 2.0	Patterns of treatment failure, toxicity, including complications associated with the intra-arterial catheter, will be summarized in tabular form.	Up to 3.5 years	Yes