CompletedNCT01099436NEO-ZOTACUpdated Jan 21, 2020

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

A Phase 3 interventional study of cyclophosphamide and docetaxel in Breast Cancer, sponsored by Borstkanker Onderzoek Groep. Completed at 1 site in Netherlands. Open to female participants aged 18 Years to 120 Years. Per ClinicalTrials.gov, last updated 2020-01-21.

Sponsored by Borstkanker Onderzoek Groep · Phase 3, Interventional, and Treatment

Phase: Phase 3
Study type: Interventional
Enrollment: 250
Allocation: Randomized
Ages: 18 Years to 120 Years
Sex: Female

Study 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.

Read the 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.

Conditions studied

Breast Cancer

Browse trials for

Breast Neoplasms 12,520

Keywords

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

Who can participate

Ages eligible: 18 Years to 120 Years
Sexes eligible: Female
Accepts healthy volunteers: No

Eligibility 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

Study design

Phase: Phase 3
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel assignment
Masking: None (open label)
Enrollment: 250 participants (actual)

Study arms

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

Interventions

Drugcyclophosphamide
Drugdocetaxel
Drugdoxorubicin hydrochloride
Drugzoledronic acid
Procedureneoadjuvant therapy

What researchers measure

Primary outcomes

Pathologic complete response after neoadjuvant chemotherapy with or without zoledronic
Time frame: after surgery

Secondary outcomes

Correlation of clinical response with pathological responses of both treatment arms
Time frame: after surgery
Disease-free survival
Time frame: 3 and 5 years
Overall survival
Time frame: 3 and 5 years
Safety and tolerability
Time frame: during treatment
Heterogeneity of the ER/PR and HER2 measurement in core biopsy and the surgical specimen
Time frame: at surgery

Study locations

1 site

Leiden University Medical Center
Leiden, 2300 RC, Netherlands

References and documents

Publications

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. PubMed 31455425 ↗
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. PubMed 26738606 ↗

Registry details

Key details

Study ID: NCT01099436
Lead sponsor: Borstkanker Onderzoek Groep
Collaborators: Dutch Cancer Society, Amgen, Sanofi, Novartis
Responsible party: Sponsor
First posted: Apr 7, 2010
Start date: Apr 2010
Primary completion: Apr 2012
Completion: Sep 2013
Last update: Jan 21, 2020

Study contacts

Judith Kroep, MD

principal investigator · Leiden University Medical Center

Oversight

Data monitoring committee: Yes

View the source record on ClinicalTrials.gov ↗

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