Capecitabine and Oxaliplatin in Treating Patients With Metastatic Breast Cancer - Full Text View

Sponsors and Collaborators:	Hoosier Oncology Group Sanofi-Aventis Hoffmann-La Roche Walther Cancer Institute
Information provided by:	Hoosier Oncology Group
ClinicalTrials.gov Identifier:	NCT00216021

Purpose

In vitro data suggest synergy between oxaliplatin and 5-FU. The combination of oxaliplatin with 5-fluorouracil produced objective response rates ranging from 27-34% in two studies of patients with prior chemotherapy. Capecitabine was designed as an orally administered, tumor selective fluoropyrimidine, preferentially converted to 5-FU at the tumor site by the higher levels of pyrimidine nucleoside phosphorylase (PyNPase) in tumor tissues compared to normal tissues. The end result is higher concentrations of 5-fluorouracil in tumor relative to surrounding normal tissue. This trial will investigate the activity of this novel capecitabine/oxaliplatin (CAPOX) combination in patients with advanced disease. In addition, an exploratory analysis will correlate response with thymidine synthase and thymidine phosphorylase expression in primary tumor samples.

Condition	Intervention	Phase
Metastatic Breast Cancer	Drug: Capecitabine Drug: Oxaliplatin	Phase II

Genetics Home Reference related topics: breast cancer

MedlinePlus related topics: Breast Cancer Cancer

Drug Information available for: Capecitabine Oxaliplatin

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Non-Randomized, Open Label, Uncontrolled, Single Group Assignment, Safety/Efficacy Study
Official Title:	A Phase II Trial of Capecitabine and Oxaliplatin (CAPOX) in Patients With Metastatic Breast Cancer: Hoosier Oncology Group BRE03-60

Further study details as provided by Hoosier Oncology Group:

Primary Outcome Measures:

- To determine the objective response rate (CR+PR) of capecitabine and oxaliplatin (CAPOX) in patients with metastatic breast cancer. [ Time Frame: 36 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

To measure time to progression · [ Time Frame: 36 months ] [ Designated as safety issue: No ]
To determine rate of clinical benefit response (CR + PR + SD > 6 months). · [ Time Frame: 36 months ] [ Designated as safety issue: No ]
To determine toxicity rate of CAPOX in this patient population.· [ Time Frame: 36 months ] [ Designated as safety issue: Yes ]
To explore potential correlations between thymidine synthase (TS), thymidine phosphorylase (TP) and dihydropyrimidine dehydrogenase (DPD) expression in the primary tumor with response. [ Time Frame: 36 months ] [ Designated as safety issue: No ]

Enrollment:	25
Study Start Date:	March 2004
Study Completion Date:	June 2007

Arms	Assigned Interventions
1: Active Comparator Capecitabine + Oxaliplatin	Drug: Capecitabine Capecitabine 825 mg/m2 po bid, days 1-14 Drug: Oxaliplatin Oxaliplatin 100 mg/m2 IV, day 1

Detailed Description:

OUTLINE: This is a multi-center study.

CAPOX (21 day cycle):

Capecitabine 825 mg/m2 orally twice daily Days 1-14.
Oxaliplatin 100 mg/m2 intravenously Day 1

Patients may continue combination therapy until progression or toxicity intervenes. Patients who discontinue either agent due to toxicity may, at the investigators discretion, continue therapy with the remaining single agent on study.

ECOG performance status 0 or 1

Hematopoietic:·

ANC > 1,200/mm3·
Platelets > 100,000/mm3

Hepatic:·

Total bilirubin < 1.5 x ULN·
AST < 2 x ULN (up to 5 x ULN in patients with known liver involvement)

Renal:·

Serum creatinine < 1.5 x ULN and estimated creatinine clearance >50ml/min as calculated with Cockroft-Gault equation

Cardiovascular:·

No clinically significant cardiac disease (e.g. congestive heart failure, symptomatic coronary artery disease and cardiac arrhythmias not well controlled with medication) or myocardial infarction within the last 12 months.

Eligibility

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

Criteria

Inclusion Criteria:

Histologic or cytologic diagnosis of breast cancer with evidence of (1) unresectable, locally recurrent, or (2) metastatic disease.·
Patients with HER2 positive (3+ overexpression by IHC or gene amplification by FISH) are eligible only if they have had prior trastuzumab therapy.·
At least one measurable lesion as defined by the RECIST.
Prior radiation therapy is allowed as long as the irradiated area is not the only source of measurable disease.

Exclusion Criteria:

No prior therapy with capecitabine or oxaliplatin in any setting
No prior therapy with other platinum compounds·
No other forms of cancer therapy including radiation, chemotherapy and hormonal therapy within 21 days prior to beginning protocol therapy.·
No prior unanticipated severe reaction to fluoropyrimidine therapy, or known sensitivity to 5-fluorouracil.·
No prior fluoropyrimidine therapy for metastatic disease is allowed. Prior adjuvant fluoropyrimidine therapy is allowed if completed > 12 months from study entry.·
Maximum of one prior chemotherapy regimen for unresectable, locally recurrent or metastatic disease·
No symptomatic brain metastasis. ·
No evidence of serious concomitant systemic disorders incompatible with the study ·
No peripheral neuropathy ·
No major surgery within 28 days prior to beginning protocol therapy.·
Negative pregnancy test·
No female patients currently breastfeeding·
No malabsorption syndrome·
No evidence of serious concomitant systemic disorders incompatible with the study·
Patients must not be treated with any of the following while on protocol therapy or within 28 days prior to beginning protocol therapy: sorivudine, brivudine, cimetidine, allopurinol.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00216021

Locations

United States, Delaware
Helen F. Graham Cancer Center
Newark, Delaware, United States, 19713
United States, Illinois
Medical & Surgical Specialists, LLC
Galesburg, Illinois, United States, 61401
United States, Indiana
Medical Consultants, P.C.
Muncie, Indiana, United States, 47303
Community Regional Cancer Center
Indianapolis, Indiana, United States, 46256
Quality Cancer Center (MCGOP)
Indianapolis, Indiana, United States, 46202
Indiana University Cancer Center
Indianapolis, Indiana, United States, 46202
AP&S Clinic
Terre Haute, Indiana, United States, 47804
Elkhart Clinic
Elkhart, Indiana, United States, 46515
Center for Cancer Care, Inc., P.C.
New Albany, Indiana, United States, 47150
Oncology Hematology Associates of SW Indiana
Evansville, Indiana, United States, 47714
Northern Indiana Cancer Research Consortium
South Bend, Indiana, United States, 46601

Sponsors and Collaborators

Hoosier Oncology Group

Sanofi-Aventis

Hoffmann-La Roche

Walther Cancer Institute

Investigators

Study Chair:

Kathy Miller, M.D.

Hoosier Oncology Group, LLC

More Information

Hoosier Oncology Group Home Page This link exits the ClinicalTrials.gov site

Responsible Party:	Hoosier Oncology Group ( Kathy Miller, M.D. )
Study ID Numbers:	HOG BRE03-60
Study First Received:	September 9, 2005
Last Updated:	May 7, 2008
ClinicalTrials.gov Identifier:	NCT00216021
Health Authority:	United States: Institutional Review Board

Keywords provided by Hoosier Oncology Group:

Breast Cancer

Study placed in the following topic categories:

Oxaliplatin
Capecitabine
Skin Diseases
Breast Neoplasms
Breast Diseases

Additional relevant MeSH terms:

Antimetabolites
Neoplasms
Antimetabolites, Antineoplastic
Neoplasms by Site

Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on January 14, 2009