Neo-Adjuvant Chemotherapy (TAC) With or Without Zoledronic Acid in Treating HER2-negative Breast Cancer Patients - Full Text View

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:

Genetics Home Reference related topics: breast cancer

MedlinePlus related topics: Breast Cancer Cancer

Drug Information available for: Cyclophosphamide Triamcinolone diacetate Triamcinolone acetonide Triamcinolone Triamcinolone hexacetonide Doxorubicin Doxorubicin hydrochloride Docetaxel Zoledronic acid

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 (Adult, Senior)
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

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

de Groot S, Charehbili A, van Laarhoven HW, Mooyaart AL, Dekker-Ensink NG, van de Ven S, Janssen LG, Swen JJ, Smit VT, Heijns JB, Kessels LW, van der Straaten T, Böhringer S, Gelderblom H, van der Hoeven JJ, Guchelaar HJ, Pijl H, Kroep JR; Dutch Breast Cancer Research Group. Insulin-like growth factor 1 receptor expression and IGF1R 3129G > T polymorphism are associated with response to neoadjuvant chemotherapy in breast cancer patients: results from the NEOZOTAC trial (BOOG 2010-01). Breast Cancer Res. 2016 Jan 6;18(1):3. doi: 10.1186/s13058-015-0663-3.


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 Neoplasms by Site Neoplasms Breast Diseases Skin Diseases Cyclophosphamide Docetaxel Liposomal doxorubicin Doxorubicin Zoledronic acid Diphosphonates Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs	Antirheumatic Agents Antineoplastic Agents, Alkylating Alkylating Agents Molecular Mechanisms of Pharmacological Action Antineoplastic Agents Myeloablative Agonists Tubulin Modulators Antimitotic Agents Mitosis Modulators Antibiotics, Antineoplastic Topoisomerase II Inhibitors Topoisomerase Inhibitors Enzyme Inhibitors Bone Density Conservation Agents

ClinicalTrials.gov processed this record on September 23, 2016

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