Capecitabine, Oxaliplatin and Trastuzumab in Treating Patients With HER2 Positive Metastatic Breast Cancer

NCT ID: NCT00216073

Last Updated: 2011-05-02

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 11 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2004-03-31
• Study Completion Date: 2006-10-31

Brief Summary

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. Trastuzumab is synergistic in vitro with multiple chemotherapeutic agents including the platinum compounds. Studies have shown the efficacy of trastuzumab combined with chemotherapy in patients with HER2 overexpressing metastatic breast cancer. This trial will investigate the activity of capecitabine and oxaliplatin administered with trastuzumab (CAPOX-T) in patients with HER2 overexpressing in patients with advanced disease.

Detailed Description

OUTLINE: This is a multi-center study.

• CAPOX-T (21 day cycle):Capecitabine 825 mg/m2 orally twice daily Days 1-14Oxaliplatin 100 mg/m2 intravenously Day 1
• Trastuzumab : 6 mg/kg intravenously Day 1.8mg/kg loading dose should be given in cycle 1 for patients without previous trastuzumab therapy only.

Patients may continue combination therapy until progression or toxicity intervenes. Patients who discontinue either or both cytotoxic agents due to toxicity may, at the investigators discretion, continue therapy with the remaining agents on study until progressive disease

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.·
• LVEF > LLN by MUGA or ECHO

Conditions

Metastatic Breast Cancer

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

1

Capecitabine + Oxaliplatin + trastuzumab. Patients must be HER2 positive.

Group Type: ACTIVE_COMPARATOR

Capecitabine

Intervention Type: DRUG

Capecitabine 825 mg/m2 po bid, days 1-14

Oxaliplatin

Intervention Type: DRUG

Oxaliplatin 100 mg/m2 IV, day 1

Trastuzumab

Intervention Type: DRUG

Trastuzumab 6mg/kg IV, day 1. 8 mg/kg loading dose given in cycle 1 for patients without previous trastuzumab therapy only.

Interventions

Capecitabine

Capecitabine 825 mg/m2 po bid, days 1-14

Intervention Type: DRUG

Oxaliplatin

Oxaliplatin 100 mg/m2 IV, day 1

Intervention Type: DRUG

Trastuzumab

Trastuzumab 6mg/kg IV, day 1. 8 mg/kg loading dose given in cycle 1 for patients without previous trastuzumab therapy only.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Histologic or cytologic diagnosis of breast cancer with evidence of (1) unresectable, locally recurrent, or (2) metastatic disease.·
• HER2 gene amplification by FISH. HER protein overexpression by immunohistochemistry will not be sufficient for entry.·
• At least one measurable lesion as defined by the RECIST.
• Prior hormonal therapy for metastatic disease is allowed.
• Maximum of one prior chemotherapy regimen or trastuzumab-containing regimen for unresectable, locally recurrent or metastatic disease
• 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.·
• 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 current 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Sanofi

INDUSTRY

Sponsor Role: collaborator

Hoffmann-La Roche

INDUSTRY

Sponsor Role: collaborator

Walther Cancer Institute

OTHER

Sponsor Role: collaborator

Hoosier Cancer Research Network

OTHER

Sponsor Role: lead

Responsible Party

Hoosier Oncology Group

Principal Investigators

Kathy Miller, M.D.

Role: STUDY_CHAIR

Hoosier Oncology Group, LLC

Locations

Medical & Surgical Specialists, LLC

Galesburg, Illinois, United States

Cancer Care Center of Southern Indiana

Bloomington, Indiana, United States

Elkhart Clinic

Elkhart, Indiana, United States

Fort Wayne Oncology & Hematology, Inc

Fort Wayne, Indiana, United States

Indiana University Cancer Center

Indianapolis, Indiana, United States

Quality Cancer Center (MCGOP)

Indianapolis, Indiana, United States

Community Regional Cancer Center

Indianapolis, Indiana, United States

Medical Consultants, P.C.

Muncie, Indiana, United States

Northern Indiana Cancer Research Consortium

South Bend, Indiana, United States

AP&S Clinic

Terre Haute, Indiana, United States

Center for Hematology/Oncology of S. Michigan

Jackson, Michigan, United States

Countries

United States

Related Links

http://hoosieroncologygroup.org/

Hoosier Oncology Group Home Page

Other Identifiers

HOG BRE03-61

Identifier Type: -

Identifier Source: org_study_id