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

Metastatic Breast Cancer Clinical Trial

Official title:

A Phase II Trial of Capecitabine, Oxaliplatin and Trastuzumab (CAPOX-T) in Patients With HER-2 Positive Metastatic Breast Cancer: Hoosier Oncology Group BRE03-61

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00216073
• Other study ID #: HOG BRE03-61
• Status: Terminated
• Phase: Phase 2
• First received: September 9, 2005
• Last updated: April 29, 2011
• Start date: March 2004
• Est. completion date: October 2006

Study information

• Verified date: April 2011
• Source: Hoosier Cancer Research Network
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 11
• Est. completion date: October 2006
• Est. primary completion date: October 2006
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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.

Study Design

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

Related Conditions & MeSH terms

• Breast Neoplasms
• Metastatic Breast Cancer

Intervention

Drug:
• Capecitabine
Capecitabine 825 mg/m2 po bid, days 1-14
• Oxaliplatin
Oxaliplatin 100 mg/m2 IV, day 1
• Trastuzumab
Trastuzumab 6mg/kg IV, day 1. 8 mg/kg loading dose given in cycle 1 for patients without previous trastuzumab therapy only.

Locations

Country	Name	City	State
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	Medical & Surgical Specialists, LLC	Galesburg	Illinois
United States	Community Regional Cancer Center	Indianapolis	Indiana
United States	Indiana University Cancer Center	Indianapolis	Indiana
United States	Quality Cancer Center (MCGOP)	Indianapolis	Indiana
United States	Center for Hematology/Oncology of S. Michigan	Jackson	Michigan
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

Sponsors (4)

Lead Sponsor	Collaborator
Hoosier Cancer Research Network	Hoffmann-La Roche, Sanofi, Walther Cancer Institute

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	- · To determine the objective response rate (CR+PR) of capecitabine, oxaliplatin and trastuzumab(CAPOX-T) in patients with HER2 positive metastatic breast cancer.		18 months	No
Secondary	To measure time to progression		18 months	No
Secondary	To determine rate of clinical benefit response (CR + PR + SD > 6 months)		18 months	No
Secondary	To determine toxicity rate of CAPOX-T in this patient population		18 months	Yes
Secondary	To explore potential correlations between changes in HER2 circulating extracellular domain in the primary tumor with response		18 months	No

External Links

•   Hoosier Oncology Group Home Page