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Capecitabine and Oxaliplatin in Treating Patients With Metastatic Breast Cancer

Phase 2
Completed
Conditions
Metastatic Breast Cancer
Interventions
Registration Number
NCT00216021
Lead Sponsor
Hoosier Cancer Research Network
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. 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.

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.

Recruitment & Eligibility

Status
COMPLETED
Sex
Female
Target Recruitment
25
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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Single Group AssignmentCapecitabineCapecitabine + Oxaliplatin
Single Group AssignmentOxaliplatinCapecitabine + Oxaliplatin
Primary Outcome Measures
NameTimeMethod
- To determine the objective response rate (CR+PR) of capecitabine and oxaliplatin (CAPOX) in patients with metastatic breast cancer.36 months
Secondary Outcome Measures
NameTimeMethod
To determine rate of clinical benefit response (CR + PR + SD > 6 months). ·36 months
To explore potential correlations between thymidine synthase (TS), thymidine phosphorylase (TP) and dihydropyrimidine dehydrogenase (DPD) expression in the primary tumor with response.36 months
To determine toxicity rate of CAPOX in this patient population.·36 months
To measure time to progression ·36 months

Trial Locations

Locations (11)

Medical & Surgical Specialists, LLC

🇺🇸

Galesburg, Illinois, United States

Indiana University Cancer Center

🇺🇸

Indianapolis, Indiana, United States

Helen F. Graham Cancer Center

🇺🇸

Newark, Delaware, United States

Quality Cancer Center (MCGOP)

🇺🇸

Indianapolis, Indiana, United States

Elkhart Clinic

🇺🇸

Elkhart, Indiana, United States

Northern Indiana Cancer Research Consortium

🇺🇸

South Bend, Indiana, United States

Community Regional Cancer Center

🇺🇸

Indianapolis, Indiana, United States

Oncology Hematology Associates of SW Indiana

🇺🇸

Evansville, Indiana, United States

Medical Consultants, P.C.

🇺🇸

Muncie, Indiana, United States

AP&S Clinic

🇺🇸

Terre Haute, Indiana, United States

Center for Cancer Care, Inc., P.C.

🇺🇸

New Albany, Indiana, United States

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