Neoplasms

Symptoms and General Pathology

All Conditions

Skin and Connective Tissue Diseases

Nutritional and Metabolic Diseases

Rare Diseases

Neoplasm Metastasis

Breast Neoplasms

Recurrence

Breast Neoplasms, Male

Hypercalcemia

Breast Diseases

Skin Diseases

Neoplastic Processes

Metabolic Diseases

Calcium Metabolism Disorders

Water-Electrolyte Imbalance

Breast Cancer, Male

Bone Density Conservation Agents

All Drugs and Chemicals

Zoledronic Acid

Ibandronic Acid

4 mg via intravenous infusion (iv) over a minimum of 15 minutes in at least 100mls of saline every 4 weeks over 96 weeks

ibandronate sodium

zoledronic acid

Zoledronic acid 4 mg by intravenous infusion every 4 weeks.

Zolendronic Acid

Peter J. Barrett Lee, MD

RATIONALE: Ibandronate and zoledronate may help relieve some of the symptoms caused by bone metastases. It is not yet know whether ibandronate is more effective than zoledronate in treating bone metastases from breast cancer.

PURPOSE: This randomized phase III trial is studying ibandronate to see how well it works compared with zoledronate in treating patients with newly diagnosed bone metastases from breast cancer.

OBJECTIVES:

Primary

* Compare the efficacy, in terms of reducing frequency and timing of skeletal-related events (SREs), of ibandronate vs zoledronate in patients with newly diagnosed bone metastases secondary to breast cancer.

Secondary

* Compare the median time to first SRE in patients treated with these regimens.
* Compare the percentage of patients experiencing a SRE after treatment with these regimens.
* Compare the number of occult vertebral fractures present in patients at the end of treatment with these regimens.
* Compare the pain and analgesic scores and quality of life of patients treated with these regimens.
* Compare the number of patients developing renal dysfunction or hypocalcemia during the study period.
* Compare the number of patients developing osteonecrosis of the jaw during study treatment and follow-up.
* Compare the overall survival of these patients at 96 weeks and at 5 years.
* Compare the health-resource usage of patients treated with these regimens.

OUTLINE: This is a randomized, open-label, parallel-group, controlled, multicenter study. Patients are randomized to 1 of 2 treatment arms.

* Arm I: Patients receive zoledronate IV over 15 minutes on day 1. Treatment repeats every 21\* or 28 days for at least 96 weeks (24 or 32 courses) in the absence of disease progression or unacceptable toxicity.

NOTE: \*Patients who receive concurrent chemotherapy every 3 weeks receive study treatment every 21 days

* Arm II: Patients receive oral ibandronate once daily on days 1-28. Treatment repeats every 28 days for at least 96 weeks (24 courses) in the absence of disease progression or unacceptable toxicity. Patients with bone pain or hypercalcemia at study entry or those who require IV therapy due to hypercalcemia while on study may receive 1 treatment with ibandronate IV at the discretion of the supervising clinician.

Quality of life and pain are assessed at baseline, after every 3 courses, and at completion of study treatment.

After completion of study treatment, patients are followed annually for up to 3 years.

PROJECTED ACCRUAL: A total of 1,400 patients will be accrued for this study.

Ibandronate or Zoledronate in Treating Patients With Newly Diagnosed Bone Metastases From Breast Cancer

Zoledronate Versus Ibandronate Comparative Evaluation: A Randomized Phase III, Open-Label, Multicenter, Parallel Group Clinical Trial to Evaluate and Compare the Efficacy, Safety Profile and Tolerability of Oral Ibandronate Versus Intravenous Zoledronate in the Treatment of Breast Cancer Patients With Bone Metastases

Velindre NHS Trust

Wales Cancer Trials Unit

Antineoplastic Agents

Antirheumatic Agents

Anti-Infective Agents

Trastuzumab

Cyclophosphamide

Docetaxel

Taxane

Doxorubicin

Liposomal doxorubicin

Anti-Bacterial Agents

Antibiotics, Antitubercular

Enzyme Inhibitors

Zo-Nantax arm - Neoadjuvant chemotherapy with association of zoledronic acid and standard treatment with anthracycline followed taxane plus trastuzumab in locally advanced breast cancer HER2 positive HR positive/negative.

Drug:Cyclophosphamide Drug:Adriamycin Drug:Docetaxel Drug:Trastuzumab Drug: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

Zo-Nantax

Susanne C Costa, MD

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.

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.

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

Phase II Clinical Trial of Neoadjuvant Treatment With Zolendronic Acid Plus Anthracycline and Taxane in Locally Advanced Breast Cancer

Use MD Anderson calculator to quantify the minimal residual disease

Make MRI before the start of chemotherapy, after the second cycle and before surgery, and evaluate the changes in the diffusion of water

Susanne Crocamo

Clinical Oncologist

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Ibandronate or Zoledronate in Treating Patients With Newly Diagnosed Bone Metastases From Breast Cancer	NCT00326820	Breast Cancer Hypercalcemia o... Metastatic Canc...	ibandronate sod... zoledronic acid Zolendronic Aci...	18 Years -	Wales Cancer Trials Unit
ZoNantax - Zolendronic Acid as Neoadjuvant Therapy Plus Anthracycline and Taxane in Locally Advanced Breast Cancer	NCT01472146	Breast Cancer Breast Disease Neoplasms Neoplasms by Si...	Zo-Nantax	18 Years - 75 Years	Instituto Nacional de Cancer, Brazil
ZoNantax - Zolendronic Acid as Neoadjuvant Therapy Plus Anthracycline and Taxane in Locally Advanced Breast Cancer	NCT01472146	Breast Cancer Breast Disease Neoplasms Neoplasms by Si...	Zo-Nantax	18 Years - 75 Years	Instituto Nacional de Cancer, Brazil

Spots Global Cancer Trial Database for zolendronic acid