Study of Neoadjuvant Docetaxel and Cyclophosphamide in Locally Advanced or Node Positive Primary Breast Cancer With Companion Pharmacokinetic and Pharmacogenomic Analyses

Breast Cancer Clinical Trial

Official title: Phase 2 Study of Neoadjuvant Docetaxel and Cyclophosphamide in Locally Advanced or Node Positive Primary Breast Cancer With Companion Pharmacokinetic and Pharmacogenomic Analyses

Status Completed

Clinical Trial Summary

Primary

The purpose of this study is to evaluate tumour pathological complete response rate after six cycles of neoadjuvant docetaxel and cyclophosphamide in an Asian population.

Secondary

To assess:

1. Pharmacokinetics (PK) and pharmacogenomics (PG) of docetaxel cyclophosphamide in Asian patients,

2. Safety and toxicity of docetaxel cyclophosphamide in Asian patients, and

3. To determine efficacy of short course (3 days) filgrastim in primary and secondary prophylaxis against febrile neutropenia in patients receiving docetaxel and cyclophosphamide.

Clinical Trial Description

Study Design and Duration

Simon Optimal two-stage Phase II design will be used for this trial. With a null hypothesis of p0=5% and an alternative hypothesis of p1=20%, significance level, α=5% and power, (1-β)=90%, a total of 41 patients will be required, with 21 patients to be recruited for the first stage.

Hence, 21 to 41 patients will be recruited at National Cancer Centre Singapore over 36 months

Patient Sample

Patients with newly diagnosed, histological confirmed HER-2 negative clinically node positive or locally advanced (cT3-T4, N0-3 or cTx, T0-4, N2-N3) primary breast cancer without evidence of metastatic disease.

Dosage/ Dosage Form, Route and Dose Regimen

Node Positive or Locally Advanced HER2 Negative Breast Cancer proceed to Docetaxel 75 mg/m2 + Cyclophosphamide 600 mg/m2 q21 days x 6 proceed to surgery

NOTE: cyclophosphamide is administered by intravenous infusion over 10 minutes followed by docetaxel over 90 minutes Patients will receive further chemotherapy, radiotherapy, endocrine therapy and targeted therapy as per institutional guidelines after surgery.

Patients with clinical non-response after 4 cycles of docetaxel and cyclophosphamide are most unlikely to have a pathological complete response. Hence, discontinuation of study and cross over to an anthracycline based chemotherapy is allowed at that point at the discretion of the treating oncologist. These patients will be classified as pathological non complete response.

Patients with progressive disease at any time will discontinue study treatment and receive salvage therapy.

Efficacy Measurements

Pathological response will be assessed by evaluation of resected surgical specimen after completion of protocol treatment.

Safety Measurements

Vital signs, Eastern Cooperative Oncology Group (ECOG) performance status, adverse events (AEs), serial laboratory safety tests. Proportion of patients with febrile neutropenia despite primary prophylactic G-CSF will be reviewed when 6,12 ,18, 24 and 30 patients have been accrued. Increase in number of doses of primary prophylactic G-CSF will be implemented if the lower limit of the 95% confidence interval of proportion exceeds 20%.

Data Analysis

All patients who have received at least 1 dose of study treatment will be included in the safety and efficacy analyses.

Pharmacokinetic (PK), Pharmacogenetic (PG) and Correlative Studies

Consent will be obtained for future analysis of any stored preoperative tumour biopsy specimens for possible gene expression profiles predictive of docetaxel and cyclophosphamide. Patients will undergo blood sampling for docetaxel and cyclophosphamide PK studies on cycle 1 day 1 (see page 22 for detailed timing). Whole blood will be collected at baseline for genotyping for CYP3A4, CYP3A5, CYP2B6, CYP2C19, ALDH, GST, ABCB1, SLCO1B3, PXR, CAR, HNF4α genes

ALL PATIENTS WITH SERIOUS ADVERSE EVENTS MUST BE FOLLOWED UP FOR OUTCOME. ;

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

• NCT number: NCT01540110
• Study type: Interventional
• Source: National Cancer Centre, Singapore
• Status: Completed
• Phase: Phase 2
• Start date: August 11, 2010
• Completion date: October 20, 2015