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

NCT01099436 | Completed Phase 3 DMC

• 4 other identifiers: BOOG-2010-01CDR0000669246BOOG-NEO-ZOTAC2009-016932-11
• Study Type: interventional
• Target: 250
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Breast Cancer

Keywords

HER2-negative breast cancer; stage II breast cancer; stage IIIA breast cancer; stage IIIB breast cancer; stage IIIC breast cancer

Outcome Measures

Primary Outcomes (1)

• Pathologic complete response after neoadjuvant chemotherapy with or without zoledronic

  after surgery

Secondary Outcomes (5)

• Correlation of clinical response with pathological responses of both treatment arms

  after surgery

• Disease-free survival

  3 and 5 years

• Overall survival

  3 and 5 years

• Safety and tolerability

  during treatment

• Heterogeneity of the ER/PR and HER2 measurement in core biopsy and the surgical specimen

  at surgery

Study Arms (2)

TAC + Zoledronic acid

EXPERIMENTAL

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

TAC

ACTIVE COMPARATOR

six cycles of docetaxel (Taxotere®), Adriamycin® (endoxan) and Cyclofosfamide (TAC)

Drug: cyclophosphamide; Drug: docetaxel; Drug: doxorubicin hydrochloride; Procedure: neoadjuvant therapy

Interventions

cyclophosphamide DRUG

TAC; TAC + Zoledronic acid

docetaxel DRUG

TAC; TAC + Zoledronic acid

doxorubicin hydrochloride DRUG

TAC; TAC + Zoledronic acid

zoledronic acid DRUG

TAC + Zoledronic acid

neoadjuvant therapy PROCEDURE

TAC; TAC + Zoledronic acid

Eligibility Criteria

• Age: 18 Years - 120 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Borstkanker Onderzoek Groep: lead
• Dutch Cancer Society: collaborator
• Amgen: collaborator
• Sanofi: collaborator
• Novartis: collaborator

Study Sites (1)

Leiden University Medical Center

Leiden, 2300 RC, Netherlands

Location

Related Publications (3)

• Adams A, Jakob T, Huth A, Monsef I, Ernst M, Kopp M, Caro-Valenzuela J, Wockel A, Skoetz N. Bone-modifying agents for reducing bone loss in women with early and locally advanced breast cancer: a network meta-analysis. Cochrane Database Syst Rev. 2024 Jul 9;7(7):CD013451. doi: 10.1002/14651858.CD013451.pub2.

  PMID: 38979716 DERIVED

• de Groot S, Pijl H, Charehbili A, van de Ven S, Smit VTHBM, Meershoek-Klein Kranenbarg E, Heijns JB, van Warmerdam LJC, Kessels LW, Dercksen MW, Pepels MJAE, van Laarhoven HWM, Vriens BEPJ, Putter H, Fiocco M, Liefers GJ, van der Hoeven JJM, Nortier JWR, Kroep JR; Dutch Breast Cancer Research Group. Addition of zoledronic acid to neoadjuvant chemotherapy is not beneficial in patients with HER2-negative stage II/III breast cancer: 5-year survival analysis of the NEOZOTAC trial (BOOG 2010-01). Breast Cancer Res. 2019 Aug 28;21(1):97. doi: 10.1186/s13058-019-1180-6.

  PMID: 31455425 DERIVED

• 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, Bohringer 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.

  PMID: 26738606 DERIVED

Related Links

• Clinical trial summary BOOG website

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Cyclophosphamide; Docetaxel; Doxorubicin; Zoledronic Acid; Neoadjuvant Therapy

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Diterpenes; Terpenes; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Diphosphonates; Organophosphonates; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Combined Modality Therapy; Therapeutics

Study Officials

• Judith Kroep, MD

  Leiden University Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 6, 2010
• First Posted: April 7, 2010
• Study Start: April 1, 2010
• Primary Completion: April 1, 2012
• Study Completion: September 1, 2013
• Last Updated: January 21, 2020

Record last verified: 2020-01

Locations

NL (1)