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

Primary Purpose

Breast Cancer, Breast Disease, Neoplasms

Status

Completed

Phase

Phase 2

Locations

Brazil

Study Type

Interventional

Intervention

Zo-Nantax

About this trial

This is an interventional treatment trial for Breast Cancer focused on measuring Neoadjuvant therapy, Breast cancer HER2 positive, zolendronic acid

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)FemaleDoes not accept healthy volunteers

Inclusion Criteria:

Stage IIA to IIIB HER-2 positive breast cancer
ECOG performance ≤ 2
Adequate hematologic function with:
- Absolute neutrophil count (ANC)> 1500/mm³
- Platelets ≥ 100.000/mm³
- hemoglobin ≥ 9g/dL
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
Adequate cardiac function
- Left ventricular ejection fraction (LVEF)with institutional normal range
Knowledge of the investigational nature of the study and ability to provide consent for study participation

Exclusion Criteria:

Previous diagnostic of breast or other cancer
Pregnancy
Metastatic breast cancer
Bilateral, synchronous breast cancer
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
Neuropathy grade > 2 by the Common Terminology Criteria for Adverse Events version 3.0 (CTCAE v3.0)

Sites / Locations

Hospital do Cancer III - INCA

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Zometa neoadjuvant HER2 breast cancer

Arm Description

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

Outcomes

Primary Outcome Measures

Evaluate the residual cancer burden (RCB)

Use MD Anderson calculator to quantify the minimal residual disease

Secondary Outcome Measures

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

Assessment of the difference in gene expression according to treatment response

Through microarray assays

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

Full Information

NCT ID

NCT01472146

First Posted

September 20, 2011

Last Updated

May 4, 2017

Sponsor

Susanne Crocamo

1. Study Identification

Unique Protocol Identification Number

NCT01472146

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

May 2017

Overall Recruitment Status

Completed

Study Start Date

October 2011 (Actual)

Primary Completion Date

July 2016 (Actual)

Study Completion Date

May 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor-Investigator

Name of the Sponsor

Susanne Crocamo

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Breast Cancer, Breast Disease, Neoplasms, Neoplasms by Site

Keywords

Neoadjuvant therapy, Breast cancer HER2 positive, zolendronic acid

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

58 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Zometa neoadjuvant HER2 breast cancer

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

Zo-Nantax

Other Intervention Name(s)

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

Intervention Description

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

Primary Outcome Measure Information:

Title

Evaluate the residual cancer burden (RCB)

Description

Use MD Anderson calculator to quantify the minimal residual disease

Time Frame

6 months

Secondary Outcome Measure Information:

Title

Assessing the tolerance to standard neoadjuvant treatment plus zolendronic acid,according to the common toxicity criteria Terminology Criteria for Adverse Events version 3.0.

Description

CTC 4.0

Time Frame

6 months

Title

Assessment of the difference in gene expression according to treatment response

Description

Through microarray assays

Time Frame

6 months

Title

Prediction of pathological response by MRI calculated from the sequence of apparent diffusion coefficient (ADC)

Description

Make MRI before the start of chemotherapy, after the second cycle and before surgery, and evaluate the changes in the diffusion of water

Time Frame

4 months

10. Eligibility

Sex

Female

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

75 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Stage IIA to IIIB HER-2 positive breast cancer ECOG performance ≤ 2 Adequate hematologic function with: Absolute neutrophil count (ANC)> 1500/mm³ Platelets ≥ 100.000/mm³ hemoglobin ≥ 9g/dL 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 Adequate cardiac function Left ventricular ejection fraction (LVEF)with institutional normal range Knowledge of the investigational nature of the study and ability to provide consent for study participation Exclusion Criteria: Previous diagnostic of breast or other cancer Pregnancy Metastatic breast cancer Bilateral, synchronous breast cancer 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 Neuropathy grade > 2 by the Common Terminology Criteria for Adverse Events version 3.0 (CTCAE v3.0)

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Susanne C Costa, MD

Organizational Affiliation

Hospital do Cancer III - INCA

Official's Role

Principal Investigator

Facility Information:

Facility Name

Hospital do Cancer III - INCA

City

Rio de Janeiro

ZIP/Postal Code

20560-120

Country

Brazil

12. IPD Sharing Statement

Plan to Share IPD

IPD Sharing Plan Description

I don't plan to share IPD

Learn more about this trial

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

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