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

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2013 by Instituto Nacional de Cancer, Brazil
Sponsor:
Information provided by (Responsible Party):
Susanne Crocamo, Instituto Nacional de Cancer, Brazil
ClinicalTrials.gov Identifier:
NCT01472146
First received: September 20, 2011
Last updated: March 4, 2013
Last verified: March 2013
  Purpose

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.


Condition Intervention Phase
Breast Cancer
Breast Disease
Neoplasms
Neoplasms by Site
Drug: cyclophosphamide, Adriamycin, Docetaxel, Trastuzumab, Zolendronic acid
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Clinical Trial of Neoadjuvant Treatment With Zolendronic Acid Plus Anthracycline and Taxane in Locally Advanced Breast Cancer

Resource links provided by NLM:


Further study details as provided by Instituto Nacional de Cancer, Brazil:

Primary Outcome Measures:
  • Evaluate the residual cancer burden (RCB) [ Time Frame: 6 months ] [ Designated as safety issue: No ]

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. [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
  • Assessment of the difference in gene expression according to treatment response [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Prediction of pathological response by MRI calculated from the sequence of apparent diffusion coefficient (ADC) [ Time Frame: 4 months ] [ Designated as safety issue: No ]

Estimated Enrollment: 56
Study Start Date: October 2011
Estimated Study Completion Date: November 2014
Estimated Primary Completion Date: August 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Zometa neoadjuvant HER2 breast cancer

Association of zoledronic acid with standard treatment with anthracycline followed taxane plus trastuzumab in locally advanced breast cancer HER2 positive.

Drug:Cyclophosphamide Drug:Adriamycin Drug:Docetaxel Drug:Trastuzumab Drug:Zolendronic acid

Drug: cyclophosphamide, Adriamycin, Docetaxel, Trastuzumab, Zolendronic acid

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

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.

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01472146

Contacts
Contact: Susanne C Costa, MD 55 21 32073954 crocamo@inca.gov.br
Contact: Roberta M Sarmento, RN 55 21 32073819 rsarmento@inca.gov.br

Locations
Brazil
Hospital do Cancer III - INCA Recruiting
Rio de Janeiro, Brazil, 20560-120
Contact: Susanne C Costa, MD    55 21 32073954    crocamo@inca.gov.br   
Contact: Roberta M Sarmento, RN    55 21 32073810    rsarmento@inca.gov.br   
Principal Investigator: Susanne C Costa, MD         
Sponsors and Collaborators
Susanne Crocamo
Investigators
Principal Investigator: Susanne C Costa, MD Hospital do Cancer III - INCA
  More Information

No publications provided

Responsible Party: Susanne Crocamo, Clinical Oncologist, Instituto Nacional de Cancer, Brazil
ClinicalTrials.gov Identifier: NCT01472146     History of Changes
Other Study ID Numbers: Zo-neo2011
Study First Received: September 20, 2011
Last Updated: March 4, 2013
Health Authority: Brazil: Ministry of Health

Keywords provided by Instituto Nacional de Cancer, Brazil:
Neoadjuvant therapy
Breast cancer HER2 positive
zolendronic acid

Additional relevant MeSH terms:
Breast Neoplasms
Breast Diseases
Neoplasms
Neoplasms by Site
Skin Diseases
Cyclophosphamide
Docetaxel
Trastuzumab
Doxorubicin
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antibiotics, Antineoplastic

ClinicalTrials.gov processed this record on July 24, 2014