Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Musculoskeletal Diseases

Nutritional and Metabolic Diseases

Breast Neoplasms

Osteoporosis

Breast Diseases

Skin Diseases

Bone Diseases

Bone Diseases, Metabolic

Metabolic Diseases

Micronutrients

All Drugs and Chemicals

Antineoplastic Agents

Bone Density Conservation Agents

Vitamins

Hormones

Letrozole

Estrogens

Vitamin D

Cholecalciferol

Calcium

Calcium, Dietary

Zoledronic Acid

Progesterone

Diphosphonates

Aromatase Inhibitors

Enzyme Inhibitors

Estrogen Antagonists

Estrogen Receptor Antagonists

Hormone Antagonists

Vitamin D3

Calciferol

Participants in the upfront arm received zoledronate 4 mg i.v. on Day 1 and every 6 months until disease progression (recurrence) or the end of study. Participants also received Letrozole 2.5 daily plus calcium (1000-1200 mg) and vitamin D (400-800 IU) daily.

In lieu of a placebo arm, which was considered unethical for this trial, a delayed start arm was used. Participants who met certain clinical criteria indicating risk of lumbar spine or total hip fracture, or experienced clinical fracture unrelated to trauma or any asymptomatic fracture discovered at the Month 36 scheduled visit, were started on zoledronate 4 mg i.v. and for every 6 months until disease progression (recurrence) or end of study. Participants also received Letrozole 2.5 daily plus calcium (1000-1200 mg) and vitamin D (400-800 IU) daily.

Participants received Zoledronate 4 mg IV 15-minute infusion every 6 months.

Participants received Letrozole 2.5 mg daily.

Novartis Pharmaceuticals, MD

This protocol is designed to compare the effect on bone of Zoledronic Acid 4 mg every 6 months when given upfront versus delayed start (based on a post-baseline BMD T- Score below -2.0 SD at either the lumbar spine or total hip, or any clinical fracture unrelated to trauma, or an asymptomatic fracture discovered at the month 36 scheduled visit) in stage I-IIIb postmenopausal women with hormone receptor positive breast cancer who will receive Letrozole 2.5 mg daily as an adjuvant therapy.

Zoledronic Acid - Letrozole Adjuvant Synergy Trial (ZFAST) - Cancer Treatment Related Bone Loss in Postmenopausal Women With Estrogen Receptor Positive and/or Progesterone Receptor Positive Breast Cancer Receiving Adjuvant Hormonal Therapy

An Open-Label, Randomized, Multicenter Study to Evaluate the Use of Zoledronic Acid in the Prevention of Cancer Treatment-Related Bone Loss in Postmenopausal Women With Estrogen Receptor Positive and/or Progesterone Receptor Positive Breast Cancer Receiving Letrozole as Adjuvant Therapy

Bone mineral density (BMD) measurements were assessed by dual energy x-ray absorptiometry (DXA). The DXA devices of participating sites were cross-calibrated and the DXA results were compiled and analyzed by a central reader. Percent change = 100\*((BMD at Month 12 - Baseline BMD)/Baseline BMD)). Missing data at month 12 were imputed by using the last observation carried forward (LOCF) method. Post-baseline non-missing data from month 6 were carried forward to month 12. Data prior to month 6 were not carried forward.

Bone mineral density (BMD) measurements were assessed by dual energy x-ray absorptiometry (DXA). The DXA devices of participating sites were cross-calibrated and the DXA results were compiled and analyzed by a central reader.

Percent change = 100\*((BMD at Time Frame - Baseline BMD)/Baseline BMD)). Missing data beyond month 12 were not imputed by LOCF.

Bone mineral density (BMD) measurements were assessed by dual energy x-ray absorptiometry (DXA). The DXA devices of participating sites were cross-calibrated and the DXA results were compiled and analyzed by a central reader.

Percent change = 100\*((BMD at Time Frame - Baseline BMD)/Baseline BMD)). Missing data at month 12 were imputed by using the LOCF method. Post-baseline non-missing data from month 6 were carried forward to month 12. Data prior to month 6 were not carried forward.

Blood samples from a subset of participants (231 participants in total) were collected to measure the sNTX and BSAP. Missing data at month 12 were imputed by using the LOCF method. Post-baseline non-missing data from months 6 and 9 were carried forward to month 12. Data prior to month 6 were not carried forward. Missing data beyond month 12 were not imputed by LOCF.

The number of participants who experienced a clinical fracture at month 36 was assessed. Initial x-ray (both AP and lateral views) of the lumbar and thoracic spine were performed at baseline to exclude participants with evidence of fracture. In addition, repeated bone scan and/or x-ray were performed at the Principal Investigator's discretion during the course of the study to confirm evidence of clinical fracture, or at month 36 if there was no evidence of clinical fracture (lumbar and thoracic spine - lateral view). X-ray films were sent to a central reader.

The median time to disease progression was assessed by Kaplan-Meier analysis. The Principal Investigator assessed each participant for disease recurrence at each visit. Further testing was performed at the discretion of the Principal Investigator and as clinically indicated. Disease progression was defined as chest wall and/or regional recurrence confirmed by positive cytology or biopsy, and/or distance recurrence of the 1) skin, subcutaneous tissue, and lymph nodes (other than local or regional), 2) bone marrow, 3) lung, 4) skeleton 5) liver and 6) central nervous system confirmed by positive cytology, biopsy, aspirate or radiology as appropriate.

The rate of change from baseline in BMD was assessed.

Novartis Pharmaceuticals

Overall, 602 participants (301 in the upfront arm and 301 in the delayed-start arm) were randomized. Of these, 600 participants (300 in each arm) were treated. One participant in the upfront arm withdrew before taking any study drug and one participant in the delayed-start arm withdrew for administrative reasons prior to taking any study drug.

Participants in the upfront arm received Zoledronic Acid 4 mg i.v. on Day 1 and every 6 months until disease progression (recurrence)or the end of study. Participants also received Femara 2.5 daily plus calcium (1000-1200 mg) and vitamin D (400-800 IU) daily.

Letrozole : Participants received 2.5 mg daily. Zoledronic Acid : Participants received Zoledronic Acid 4 mg IV 15-minute infusion every 6 months.

Zoledronic Acid Upfront

In lieu of a placebo arm, which was considered unethical for this trial, a delayed start arm was used. Participants who met certain clinical criteria indicating risk of lumbar spine or total hip fracture, or experienced clinical fracture unrelated to trauma or any asymptomatic fracture discovered at the Month 36 scheduled visit, were started on zoledronic acid 4 mg i.v. and for every 6 months until disease progression (recurrence) or end of study. Participants also received Letrozole 2.5 daily plus calcium (1000-1200 mg) and vitamin D (400-800 IU) daily.

Letrozole : Participants received 2.5 mg daily. Zoledronic Acid : Participants received Zoledronic acid 4 mg IV 15-minute infusion every 6 months.

Zoledronic Acid Delayed-start

Participants in the upfront arm received Zoledronic Acid 4 mg i.v. on Day 1 and every 6 months until disease progression (recurrence)or the end of study. Participants also received Letrozole 2.5 daily plus calcium (1000-1200 mg) and vitamin D (400-800 IU) daily.

Letrozole : Participants received 2.5 mg daily.

Zoledronic Acid : Participants received Zoledronic Acid upfront 4 mg IV 15-minute infusion every 6 months.

In lieu of a placebo arm, which was considered unethical for this trial, a delayed start arm was used. Participants who met certain clinical criteria indicating risk of lumbar spine or total hip fracture, or experienced clinical fracture unrelated to trauma or any asymptomatic fracture discovered at the Month 36 scheduled visit, were started on Zoledronic Acid 4 mg i.v. and for every 6 months until disease progression (recurrence) or end of study. Participants also received Letrozole 2.5 daily plus calcium (1000-1200 mg) and vitamin D (400-800 IU) daily.

Letrozole : Participants received 2.5 mg daily.

Zoledronic Acid : Participants received Zoledronic Acid upfront 4 mg IV 15-minute infusion every 6 months.

Total

Age, Continuous

Sex: Female, Male

Study Director

Participants in the upfront arm received Zoledronic Acid 4 mg i.v. on Day 1 and every 6 months until disease progression (recurrence)or the end of study. Participants also received Letrozole 2.5 daily plus calcium (1000-1200 mg) and vitamin D (400-800 IU) daily.

Letrozole : Participants received 2.5 mg daily.

Zoledronic Acid : Participants received Zoledronic Acid 4 mg IV 15-minute infusion every 6 months.

In lieu of a placebo arm, which was considered unethical for this trial, a delayed start arm was used. Participants who met certain clinical criteria indicating risk of lumbar spine or total hip fracture, or experienced clinical fracture unrelated to trauma or any asymptomatic fracture discovered at the Month 36 scheduled visit, were started on zoledronic acid 4 mg i.v. and for every 6 months until disease progression (recurrence) or end of study. Participants also received Letrozole 2.5 daily plus calcium (1000-1200 mg) and vitamin D (400-800 IU) daily.

Letrozole : Participants received 2.5 mg daily.

Zoledronic Acid : Participants received Zoledronic Acid 4 mg IV 15-minute infusion every 6 months.

Intent to treat (ITT population) was used. The ITT population contained all patients in the safety population for whom at least one post-baseline efficacy measurement was collected.

Percent Change From Baseline in Lumbar Spine (L1-L4) Bone Mineral Density (BMD)

2 years (n=206,202)

3 years (n=189,190)

5 years (n=140,132)

In lieu of a placebo arm, which was considered unethical for this trial, a delayed start arm was used. Participants who met certain clinical criteria indicating risk of lumbar spine or total hip fracture, or experienced clinical fracture unrelated to trauma or any asymptomatic fracture discovered at the Month 36 scheduled visit, were started on Zoledronic Acid 4 mg i.v. and for every 6 months until disease progression (recurrence) or end of study. Participants also received Letrozole 2.5 daily plus calcium (1000-1200 mg) and vitamin D (400-800 IU) daily.

Letrozole : Participants received 2.5 mg daily.

Zoledronic Acid : Participants received Zoledronic Acid 4 mg IV 15-minute infusion every 6 months.

Zoledronic Acid Delayed Start

Percent Change From Baseline in Lumbar Spine (L1-L4) BMD

12 months (n=253,256)

2 years (n=208,200)

3 years (n=187,189)

5 years (n=141,132)

Percent Change From Baseline in Total Hip BMD

sNTX, 12 months (n=87,85)

sNTX, 2 years

sNTX, 3 years

sNTX, 5 years

BSAP, 12 months (n=88,90)

BSAP, 2 years (n=63,60)

BSAP, 3 years (n=59,52)

BSAP, 5 years (n=95,102)

Percent Change From Baseline in Biochemical Markers of Bone Turnover, Serum N-Telopeptide (sNTX) and Bone-specific Alkaline Phosphatase (BSAP)

Incidence Rate of All Clinical Fractures

Time to Disease Recurrence/Relapse

Rate of Change From Baseline in Lumbar Spine (L1-L4) BMD

Rate of Change From Baseline in Total Hip BMD

Participants in the upfront arm received Zoledronic Acid 4 mg i.v. on Day 1 and every 6 months until disease progression (recurrence) or the end of study. Participants also received Letrozole 2.5 daily plus calcium (1000-1200 mg) and vitamin D (400-800 IU) daily.

Letrozole : Participants received 2.5 mg daily.

Zoledronic Acid : Participants received Zoledronic Acid 4 mg IV 15-minute infusion every 6 months.

In lieu of a placebo arm, which was considered unethical for this trial, a delayed start arm was used. Participants who met certain clinical criteria indicating risk of lumbar spine or total hip fracture, or experienced clinical fracture unrelated to trauma or any asymptomatic fracture discovered at the Month 36 scheduled visit, were started on zoledronic acid 4 mg i.v. and for every 6 months until disease progression (recurrence) or end of study. Participants also received Letrozole 2.5 daily plus calcium (1000-1200 mg) and vitamin D (400-800 IU) daily.

Letrozole : Participants received 2.5 mg daily.

Zoledronic Acid : Participants received Zoledronic acid 4 mg IV 15-minute infusion every 6 months.

Spots Global Cancer Trial Database for us32

Every month we try and update this database with for us32 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for us32

Every month we try and update this database with for us32 cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for us32 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.