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

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

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.

Study Overview

• Status: Completed
• Conditions: Neoplasms; Neoplasms by Site; Breast Cancer; Breast Disease
• Intervention / Treatment: Drug: Zo-Nantax

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 Type: Interventional
• Enrollment (Actual): 58
• Phase: Phase 2

Contacts and Locations

Study Locations

• Brazil
  • Rio de Janeiro, Brazil, 20560-120
    • Hospital do Cancer III - INCA

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

EXPERIMENTAL: Zometa neoadjuvant HER2 breast cancer; 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

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; Other Names: Cytoxan; Other Names:; Taxotere®; Zometa; Herceptin®; Adriblastine RD

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluate the residual cancer burden (RCB)	Use MD Anderson calculator to quantify the minimal residual disease	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
Assessment of the difference in gene expression according to treatment response	Through microarray assays	6 months
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

Collaborators and Investigators

• Sponsor: Susanne Crocamo
• Investigators: Principal Investigator: Susanne C Costa, MD, Hospital do Cancer III - INCA

Study record dates

Study Major Dates

• Study Start (ACTUAL): October 1, 2011
• Primary Completion (ACTUAL): July 1, 2016
• Study Completion (ACTUAL): May 1, 2017

Study Registration Dates

• First Submitted: September 20, 2011
• First Submitted That Met QC Criteria: November 11, 2011
• First Posted (ESTIMATE): November 16, 2011

Study Record Updates

• Last Update Posted (ACTUAL): May 9, 2017
• Last Update Submitted That Met QC Criteria: May 4, 2017
• Last Verified: May 1, 2017

More Information

Terms related to this study

• Keywords: Neoadjuvant therapy; zolendronic acid; Breast cancer HER2 positive
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Breast Neoplasms; Breast Diseases; Neoplasms by Site; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Antibiotics, Antineoplastic; Doxorubicin
• Other Study ID Numbers: Zo-neo2011

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: I don't plan to share IPD