Clinical trial NCT00776724: Tailored Neoadjuvant Chemotherapy for Stage II/III Breast Cancer With Tumor Size More Than 2 cm
Official title: A Randomized Phase III Study of Docetaxel/ Epirubicin Versus Tailored Regimens as Neoadjuvant Chemotherapy for Stage II/III Breast Cancer With Tumor Size More Than 2 cm
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Breast Cancer
Chemotherapy
Keywords: breast ca
phase III
Tailored neoadjuvant chemotherapy
stage II/III
Lead sponsor: National Taiwan University Hospital
Sponsor class: OTHER
First posted: 2008-10-21
Enrollment: 166
Sex: FEMALE
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a multi-center randomized phase III trial. The purpose is to evaluate and compare the pathological complete response (pCR) rates after neoadjuvant chemotherapy with tailored chemotherapeutic regimens or standard chemotherapy for stage II/III breast cancer with tumor size more than 2 cm.

Detailed description: This is a multicenter randomized phase III trial. The purpose is to evaluate and compare the pathological complete response (pCR) rates after neoadjuvant chemotherapy with tailored chemotherapeutic regimens or standard chemotherapy for stage II/III breast cancer with tumor size more than 2 cm.

For primary operable breast cancer, neoadjuvant chemotherapy is one of standard options. Pathological complete response (pCR) was associated with significantly improved long-term disease free and overall survival. Anthracycline/taxane-based chemotherapy regimens have been studied extensively in prospective trials and are the most frequently prescribed treatments in patients with breast cancer as neoadjuvant chemotherapy. Regimens that have been tested in large multicenter phase III trials and yielded pCR rates of at around 15% and up to 20% after 6 cycles of chemotherapy. Recent evidences have showed that the expression of several proteins in the tumor samples such as tau, topoisomerase II alpha (topo II), and ERCC1 can predict the tumor response to taxanes, anthracyclines, and platinums, respectively. We hypothesized that select chemotherapeutic agent according the expressions of drug sensitivity predictive biomarkers from patient's tumor sample may improve the efficacy of breast cancer treatment.

In this randomized phase III trial, TE (Docetaxel/ epirubicin) will be given in control arm since it is a highly active regimen for breast cancer. In the Tailored chemotherapy arm, 7 different combination chemotherapy regimens that containing 2 drugs among taxotere, epirubicin, cisplatin, vinorelbine, and 5FU, will be given according to the expressions of tumor biomarkers. The doses and schedules of those regimens are selected according published 1st line protocols for breast cancer. The primary endpoint is the pCR rate. After 4 cycles of neoadjuvant chemotherapy, under the assumption of pCR rate of 15% in TE arm, to achieve 80% power at the 5% level (one side) of significance for the detection of a 15% increase of pCR rate in tailored regimen arm, 134 patients in either arm should be included in the study. If a 10% drop-out rate and multi-center study variation effect are considered, totally 316 patients will be required.

Eligibility criteria: Inclusion Criteria:

* Histologically confirmed invasive, but non-inflammatory, breast carcinoma, with stage II or III disease (AJCC 7th ed)
* And, tumor size more than 2 cm in greatest diameter measured by estimated by CT scan or MRI
* Documented Her2/neu negative , including score 0, 1+, or 2+ by immunohistochemistry
* No prior radiotherapy, hormonal therapy or chemotherapy for invasive breast cancer
* Performance status of ECOG 0, 1,
* Female with age older than 20 years
* Laboratory parameter

  * Absolute neutrophil count (ANC) ≧1500/mm3
  * Total bilirubin ≦2.0 times the upper limit of normal (ULM)
  * AST or ALT ≦2.5 times the upper limit of normal (ULM)
  * Platelets ≧100,000/mm3
  * Serum creatinine ≦1.5 x ULM
  * Fasting triglyceride ≧ 70 mg/dL
* Ability to understand and willingness to sign a written informed consent document.

Exclusion Criteria:

* Evidence of metastatic breast cancer or inflammatory breast cancer
* Bilateral breast cancer, metaplastic carcinoma, or mucinous carcinoma
* Known allergy to any of the study drugs or to agents containing Cremophor.
* Serious intercurrent infections or medical illnesses that are uncontrolled or the control of which may be jeopardized by this therapy
* Psychiatric disorders or other conditions regarding the subject incapable of complying with the requirements of the protocol
* Evidence of baseline sensory or motor neuropathy
* Pregnant or breast feeding women
* Previous or current systemic malignancy with the exception of curatively treated non-melanoma skin cancer or cervical carcinoma in situ with a disease-free interval of at least 5 years

Primary outcomes:
measure: To evaluate and compare the pathological complete response (pCR) rates
timeFrame: operation after 4 cycles of neoadjuvant chemotherapy with tailored chemotherapeutic regimens or TE
Secondary outcomes:
measure: To evaluate the overall clinical response rate
timeFrame: after 4 cycles of neoadjuvant chemotherapy with tailored chemotherapeutic regimens or TE
Other outcomes:
Locations:
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
Study officials:
affiliation: Department of Oncology, National Taiwan University Hospital
name: Yen-Shen Lu, M.D., Ph.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Department of Surgery, National Taiwan University Hospital
name: Chiun-Sheng Hunag, MD,PhD
role: PRINCIPAL_INVESTIGATOR
References: