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

Breast Cancer Clinical Trial

Official title:

Phase II Clinical Trial of Neoadjuvant Treatment With Zolendronic Acid Plus Anthracycline and Taxane in Locally Advanced Breast Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01472146
• Other study ID #: Zo-neo2011
• Status: Completed
• Phase: Phase 2
• First received: September 20, 2011
• Last updated: May 4, 2017
• Start date: October 2011
• Est. completion date: May 2017

Study information

• Verified date: May 2017
• Source: Instituto Nacional de Cancer, Brazil
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 58
• Est. completion date: May 2017
• Est. primary completion date: July 2016
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 75 Years

Eligibility

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)

Related Conditions & MeSH terms

• Breast Cancer
• Breast Disease
• Breast Diseases
• Breast Neoplasms
• Neoplasms
• Neoplasms by Site

Intervention

Drug:
• Zo-Nantax
Experimental: AC,Docetaxel,Trastuzumab,Zolendronate Drug: AC Adriamycin 60mg/m2 IV plus cyclophosphamide 600mg/m2 every 21 days for 4 cycles Drug: Docetaxel Docetaxel 100 mg/m2 every 21 days for 4 cycles. Drug: Trastuzumab Trastuzumab 8mg/kg [loading dose] once then 6mg/kg IV every 21 days for 3 cycles plus docetaxel. Drug: zolendronic acid Zolendronic acid 4mg IV every 21 days for 8 cycles combine with chemotherapy

Locations

Country	Name	City	State
Brazil	Hospital do Cancer III - INCA	Rio de Janeiro

Sponsors (1)

Lead Sponsor	Collaborator
Susanne Crocamo

Country where clinical trial is conducted

Brazil, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Evaluate the residual cancer burden (RCB)	Use MD Anderson calculator to quantify the minimal residual disease	6 months
Secondary	Assessing the tolerance to standard neoadjuvant treatment plus zolendronic acid,according to the common toxicity criteria Terminology Criteria for Adverse Events version 3.0.	CTC 4.0	6 months
Secondary	Assessment of the difference in gene expression according to treatment response	Through microarray assays	6 months
Secondary	Prediction of pathological response by MRI calculated from the sequence of apparent diffusion coefficient (ADC)	Make MRI before the start of chemotherapy, after the second cycle and before surgery, and evaluate the changes in the diffusion of water	4 months