ZoNantax - Zolendronic Acid as Neoadjuvant Therapy Plus Anthracycline and Taxane in Locally Advanced Breast Cancer

Phase 2

Completed

• Conditions: Breast Cancer; Breast Disease; Neoplasms; Neoplasms by Site
• Interventions: Drug: Zo-Nantax

• Registration Number: NCT01472146
• Lead Sponsor: Susanne Crocamo

Brief Summary

The purpose of this study is to evaluate the association of zoledronic acid with standard treatment with anthracycline followed taxane plus trastuzumab in locally advanced breast cancer HER 2 positive.

Detailed Description

This trial combines zolendronic acid with anthracycline followed taxane plus trastuzumab for neoadjuvant treatment of HER 2 positive stage II/III breast cancer.

Zoledronic acid (ZOL) has activity of anti-bone resorption and shows diverse anti-tumor effects in vitro. Some chemical and biological characteristics of ZOL indicate potential for inhibition of tumor growth in pre clinical studies

The primary objective of the study is to evaluate the residual cancer burden (RCB) with the addition of zolendronic acid to standard neoadjuvant therapy. RCB is calculated as a continuous index combining pathologic measurements of primary tumor (size and cellularity) and nodal metastases (number and size). RCB index is a significant predictor of distant relapse-free survival, and can be used to define categories of near-complete response and chemotherapy resistance after neoadjuvant chemotherapy compared with currently used risk factors. Additionally, the study will collect tissue biopsies and blood before and after treatment in order to correlate clinical outcomes with gene expression and radiologic data to predictive response.

Study Timeline

• Study First Submitted: 2011-09-20
• Study Start: 2011-10
• Study First Submitted QC: 2011-11-11
• Study First Posted: 2011-11-16
• Primary Completion: 2016-07
• Status Verified: 2017-05
• Study Completion: 2017-05
• Last Update Submitted: 2017-05-04
• Last Update Posted: 2017-05-09

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 58

Inclusion Criteria

1. Stage IIA to IIIB HER-2 positive breast cancer

2. ECOG performance ≤ 2

3. Adequate hematologic function with:

   • Absolute neutrophil count (ANC)> 1500/mm³
   • Platelets ≥ 100.000/mm³
   • hemoglobin ≥ 9g/dL

4. Adequate hepatic and renal function with:

   • Serum bilirubin ≤ 1.5 x the institutional upper limit of normal (ULN)
   • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT)≤ 2.5 x the institutional upper limit of normal (ULN)
   • Alkaline phosphatase )≤ 2.5 x the institutional upper limit of normal (ULN)
   • Serum creatinine ≤ 1.5 x the institutional upper limit of normal (ULN) or calculated creatinine clearance > 50 mL/min

5. Adequate cardiac function

   • Left ventricular ejection fraction (LVEF)with institutional normal range

6. Knowledge of the investigational nature of the study and ability to provide consent for study participation

Exclusion Criteria

1. Previous diagnostic of breast or other cancer
2. Pregnancy
3. Metastatic breast cancer
4. Bilateral, synchronous breast cancer
5. Any other disease(s), psychiatric condition, metabolic dysfunction, that contraindicates the use of study drugs or that woud make the patient inappropriate for this study
6. Neuropathy grade > 2 by the Common Terminology Criteria for Adverse Events version 3.0 (CTCAE v3.0)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Zometa neoadjuvant HER2 breast cancer	Zo-Nantax	Zo-Nantax arm - Neoadjuvant chemotherapy with association of zoledronic acid and standard treatment with anthracycline followed taxane plus trastuzumab in locally advanced breast cancer HER2 positive HR positive/negative. Drug:Cyclophosphamide Drug:Adriamycin Drug:Docetaxel Drug:Trastuzumab Drug:Zolendronic acid

Primary Outcome Measures

Name	Time	Method
Evaluate the residual cancer burden (RCB)	6 months	Use MD Anderson calculator to quantify the minimal residual disease

Secondary Outcome Measures

Name	Time	Method
Assessing the tolerance to standard neoadjuvant treatment plus zolendronic acid,according to the common toxicity criteria Terminology Criteria for Adverse Events version 3.0.	6 months	CTC 4.0
Assessment of the difference in gene expression according to treatment response	6 months	Through microarray assays
Prediction of pathological response by MRI calculated from the sequence of apparent diffusion coefficient (ADC)	4 months	Make MRI before the start of chemotherapy, after the second cycle and before surgery, and evaluate the changes in the diffusion of water

Trial Locations

Locations (1)

Hospital do Cancer III - INCA; 🇧🇷 Rio de Janeiro, Brazil