Clinical trial NCT00429247: Randomized Trial With Trastuzumab Versus Observation in Breast Cancer Patients
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Breast Cancer
Keywords: Occult tumor cells
Micrometastatic cells
Cytokeratin-19
Trastuzumab
Completion of Adjuvant Treatment
Lead sponsor: University Hospital of Crete
Sponsor class: OTHER
First posted: 2007-01-31
Enrollment: 75
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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)

Primary outcomes:
measure: Compare the disease-free interval of patients with early-stage breast cancer
timeFrame: 3 years
Secondary outcomes:
measure: Elimination of CK-19 mRNA-positive CTCs.
timeFrame: Assessment of CK-19 mRNA CTCs every 3 months
Other outcomes:
Locations:
city: Heraklion
country: Greece
facility: University Hospital of Crete
state: Crete
Study officials:
affiliation: University Hospital of Crete, Dep of Medical Oncology
name: Vassilis Georgoulias, MD
role: PRINCIPAL_INVESTIGATOR
References: