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Neo-Adjuvant Chemotherapy (TAC) With or Without Zoledronic Acid in Treating HER2-negative Breast Cancer Patients (NEO-ZOTAC)

This study has been completed.
Sponsor:
Collaborators:
Dutch Cancer Society
Amgen
Sanofi
Novartis
Information provided by (Responsible Party):
Borstkanker Onderzoek Groep
ClinicalTrials.gov Identifier:
NCT01099436
First received: April 6, 2010
Last updated: July 15, 2014
Last verified: July 2014
History of Changes
  Purpose

RATIONALE: Drugs used in chemotherapy, such as doxorubicin hydrochloride, cyclophosphamide, docetaxel, and zoledronic acid, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells. It is not yet known whether combination chemotherapy is more effective when given together with zoledronic acid in treating patients with breast cancer.

PURPOSE: This randomized phase III trial is studying giving doxorubicin hydrochloride together with cyclophosphamide and docetaxel to see how well it works with or without zoledronic acid in treating patients with large resectable or locally advanced breast cancer.


Condition Intervention Phase
Breast Cancer
 Drug: cyclophosphamide
Drug: docetaxel
Drug: doxorubicin hydrochloride
Drug: zoledronic acid
Procedure: neoadjuvant therapy
 Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase III Randomized Trial With NEOadjuvant Chemotherapy (TAC) With or Without ZOledronic Acid for Patients With HER2- Negative Large Resectable or Locally Advanced Breast Cancer(NEO-ZOTAC)

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by Borstkanker Onderzoek Groep:

Primary Outcome Measures:
  • Pathologic complete response after neoadjuvant chemotherapy with or without zoledronic [ Time Frame: after surgery ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Correlation of clinical response with pathological responses of both treatment arms [ Time Frame: after surgery ] [ Designated as safety issue: No ]
  • Disease-free survival [ Time Frame: 3 and 5 years ] [ Designated as safety issue: No ]
  • Overall survival [ Time Frame: 3 and 5 years ] [ Designated as safety issue: No ]
  • Safety and tolerability [ Time Frame: during treatment ] [ Designated as safety issue: Yes ]
  • Heterogeneity of the ER/PR and HER2 measurement in core biopsy and the surgical specimen [ Time Frame: at surgery ] [ Designated as safety issue: No ]
Enrollment: 250
Study Start Date: April 2010
Study Completion Date: September 2013
Primary Completion Date: April 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: TAC + Zoledronic acid
six cycles of docetaxel (Taxotere®), Adriamycin® (endoxan) and Cyclofosfamide (TAC) and zoledronic acid (Zometa)
 Drug: cyclophosphamide Drug: docetaxel Drug: doxorubicin hydrochloride Drug: zoledronic acid Procedure: neoadjuvant therapy
Active Comparator: TAC
six cycles of docetaxel (Taxotere®), Adriamycin® (endoxan) and Cyclofosfamide (TAC)
 Drug: cyclophosphamide Drug: docetaxel Drug: doxorubicin hydrochloride Procedure: neoadjuvant therapy

Detailed Description:

OBJECTIVES:

Primary

  • To determine the value of neoadjuvant chemotherapy comprising doxorubicin hydrochloride, cyclophosphamide, and docetaxel with or without zoledronic acid in patients with HER2-negative large resectable or locally advanced breast cancer.

Secondary

  • To correlate clinical response with pathological responses in both treatment arms.
  • To evaluate the disease-free survival and overall survival of patients treated with this regimen.
  • To evaluate the safety and tolerability of adding zoledronic acid to neoadjuvant chemotherapy.
  • To evaluate heterogeneity of the ER/PR and HER2 measurement in core biopsy and the surgical specimen.

OUTLINE: Patients are randomized between 2 treatment arms.

  • Arm I: Patients receive doxorubicin hydrochloride IV, cyclophosphamide IV, and docetaxel IV on day 1. Patients also receive zoledronic acid IV over 15 minutes on day 1. Treatment repeats every 3 weeks for 6 courses in the absence of disease progression or unacceptable toxicity.
  • Arm II: Patients receive doxorubicin hydrochloride IV, cyclophosphamide IV, and docetaxel IV as in arm I. Treatment repeats every 3 weeks for 6 courses in the absence of disease progression or unacceptable toxicity.
  Eligibility
Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Histologically confirmed breast cancer

    • Large resectable or locally advanced disease

      • T2 (≥ 2 cm and positive lymph nodes), T2 (≥ 3 cm), ≥ T3, T4, any N, M0 disease
  • Measurable disease (breast and/or lymph nodes)
  • HER2-negative disease by core biopsy
  • No evidence of distant metastases (M1)
  • No prior breast cancer

PATIENT CHARACTERISTICS:

  • Female
  • Menopausal status unspecified
  • WHO performance status 0-2
  • Not pregnant or nursing
  • WBC ≥ 3.0 x 10^9/L
  • Neutrophil count ≥ 1.5 x 10^9/L
  • Platelet count ≥ 100 x 10^9/L
  • Bilirubin ≤ 1.5 times upper limit of normal (UNL)
  • ALT and/or AST ≤ 2.5 times UNL
  • Alkaline phosphatase ≤ 5 times UNL
  • Creatinine clearance ≥ 50 mL/min
  • Accessible for treatment and follow-up
  • No previous malignancy within the past 5 years except basal cell carcinoma of the skin or pre-invasive carcinoma of the cervix
  • No peripheral neuropathy > grade 2 (of any cause)
  • No other serious diseases including recent myocardial infarction, clinical signs of cardiac failure, or clinically significant arrhythmias
  • No poor dental health
  • No known hypersensitivity reaction to any of the components of the treatment
  • No medical or psychological condition that, in the opinion of the investigator, would not permit the patient to complete the study or sign meaningful informed consent

PRIOR CONCURRENT THERAPY:

  • No prior breast surgery except for biopsy
  • No prior chemotherapy or radiotherapy
  • No prior bisphosphonates
  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: NCT01099436

Locations
Netherlands
Leiden University Medical Center
Leiden, Netherlands, 2300 RC
Sponsors and Collaborators
Borstkanker Onderzoek Groep
Dutch Cancer Society
Amgen
Sanofi
Novartis
Investigators
Principal Investigator: Judith Kroep, MD Leiden University Medical Center
  More Information

Additional Information:
Clinical trial summary from the National Cancer Institute's PDQ® database  This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party: Borstkanker Onderzoek Groep
ClinicalTrials.gov Identifier: NCT01099436     History of Changes
Other Study ID Numbers: BOOG-2010-01, CDR0000669246, BOOG-NEO-ZOTAC, 2009-016932-11
Study First Received: April 6, 2010
Last Updated: July 15, 2014
Health Authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Keywords provided by Borstkanker Onderzoek Groep:
HER2-negative breast cancer
stage II breast cancer
stage IIIA breast cancer
stage IIIB breast cancer
stage IIIC breast cancer

Additional relevant MeSH terms:
Breast Neoplasms
Breast Diseases
Neoplasms
Neoplasms by Site
Skin Diseases
Diphosphonates
Doxorubicin
Liposomal doxorubicin
Zoledronic acid
Antibiotics, Antineoplastic
 Antineoplastic Agents
Bone Density Conservation Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses
Topoisomerase II Inhibitors
Topoisomerase Inhibitors

ClinicalTrials.gov processed this record on February 27, 2015