Randomized Trial With Trastuzumab Versus Observation in Breast Cancer Patients

Sponsor

University Hospital of Crete (Other)

Overall Status

Completed

CT.gov ID

NCT00429247

Collaborator

(none)

Enrollment

Location

Arms

Duration (Months)

1.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Epithelial tumor cells can be detected in the bone marrow and/or the peripheral blood [disseminated and circulating tumor cells, (DTCs) and (CTCs) respectively] of otherwise metastases-free patients with early breast cancer. Several studies have shown that the presence of these cells is an independent factor associated with an increased incidence of early disease relapse and disease-related death. In almost 50% of the patients, adjuvant chemotherapy cannot eliminate these occult tumor cells and this is also associated with a higher probability of early relapse and death. In 60-70% of the patients, DTCs and/or CTCs express the HER2/c-neu molecule and one or two administrations of their monoclonal antibody trastuzumab (HERCEPTIN) could eliminate these cells for a period ranging from 3-12 months.

Condition or Disease	Intervention/Treatment	Phase
Breast Cancer	Drug: Trastuzumab	Phase 2

Detailed Description

This pilot trial will compare the efficacy of the anti-HER2/erb-B2 monoclonal antibody trastuzumab (HERCEPTIN) given after the completion of the standard adjuvant chemotherapy and radiotherapy versus observation in patients with stage I-III operable breast cancer who have detectable cytokeratin-19 (CK-19) mRNA-positive tumor cells in the bone marrow or the peripheral blood before and/or after the adjuvant treatment.

Study Design

Study Type:

Interventional

Actual Enrollment :

75 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Pilot Randomized Phase II Study of Adjuvant Administration of Trastuzumab (HERCEPTIN) Versus Observation After the Completion of Adjuvant Chemotherapy and Radiotherapy in Patients With Stage I-III Breast Cancer Who Have Detectable Disseminated and/or Circulating Tumor Cells (DTCs and/or CTCs) in the Bone Marrow or/and the Peripheral Blood Before or/and After the Completion of Adjuvant Treatment

Study Start Date :

Feb 1, 2003

Actual Primary Completion Date :

Dec 1, 2007

Actual Study Completion Date :

Dec 1, 2007

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1 Her	Drug: Trastuzumab Trastuzumab,first administration at the dose of 8mg/Kg IV, subsequent administrations at the dose of 6mg/Kg IV,every 3 weeks for 6 cycles Other Names: Herceptin
No Intervention: 2 Follow up

Arm

Intervention/Treatment

Experimental: 1

Her

Drug: Trastuzumab

Trastuzumab,first administration at the dose of 8mg/Kg IV, subsequent administrations at the dose of 6mg/Kg IV,every 3 weeks for 6 cycles

Other Names:

Herceptin

No Intervention: 2

Follow up

Outcome Measures

Primary Outcome Measures

Compare the disease-free interval of patients with early-stage breast cancer [3 years]

Secondary Outcome Measures

Elimination of CK-19 mRNA-positive CTCs. [Assessment of CK-19 mRNA CTCs every 3 months]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

Inclusion Criteria:

Age >= 18 years.
Performance status (World Health Organization [WHO]) < 3
Adequate bone marrow function (absolute neutrophil count > 1000/mm^{3, platelet count >
100000/mm}3, hemoglobin > 9 gr/mm^3)
Adequate liver (bilirubin < 1.5 times upper limit of normal and SGOT/SGPT < 2 times upper limit of normal) and renal function ( creatinine < 2 mg/dl)
Adequate cardiac function (left ventricular ejection fraction [LVEF] > 50%).
Informed consent
Histologically or cytologically confirmed breast adenocarcinoma
Prior surgical excision of the primary breast tumor
Prior completion of standard adjuvant chemotherapy and/or radiotherapy
Locally advanced disease after the completion of neo-adjuvant chemotherapy, surgical excision and radiotherapy provided that there was no evidence of local or metastatic disease
Absence of any clinical or laboratory evidence of metastatic disease
Detection of CTCs and/or DTCs (when it could be feasible) before the initiation and/or after the completion of adjuvant chemotherapy and/or radiotherapy
Expression of HER2/c-neu on the primary tumor is not mandatory

Exclusion Criteria:

Other invasive malignancy within the past 5 years except nonmelanoma skin cancer
Other concurrent uncontrolled illness
Psychiatric illness or social situation that would preclude study compliance
Pregnant or nursing
Positive pregnancy test
History of allergic reaction attributed to trastuzumab (HERCEPTIN)