Pan African Clinical Trials Registry
South African Medical Research Council, South African Cochrane Centre
PO Box 19070, Tygerberg, 7505, South Africa
Telephone: +27 21 938 0506 / +27 21 938 0834 Fax: +27 21 938 0836
Email: pactradmin@mrc.ac.za Website: pactr.samrc.ac.za
Trial no.: PACTR202112813934276 Date of Approval: 20/12/2021
Trial Status: Registered in accordance with WHO and ICMJE standards
TRIAL DESCRIPTION
Public title Delayed Versus Immediate Use Of Zoledronic Acid For Postmenopausal Patients With ER/PR Positive Early Breast Cancer Who Are Using Adjuvant Letrozole
Official scientific title Delayed Versus Immediate Use Of Zoledronic Acid For Postmenopausal Patients With ER/PR Positive Early Breast Cancer Who Are Using Adjuvant Letrozole
Brief summary describing the background and objectives of the trial Aromatase inhibitors (AIs) are accepted adjuvant endocrine therapy in postmenopausal women (PMW) with hormone receptor-positive early breast cancer (EBC) with efficacy superior to tamoxifen (TAM) [1–3], but with increased bone loss [4]. TAM antagonizes tumor-cell estrogen receptors (ERs), whereas AIs block peripheral-tissue estrogen synthesis. In the Arimidex, Tamoxifen, Alone or in Combination (ATAC) trial, 5-year fracture risk with anastrozole was 44% higher than that with TAM [2]. Similar fracture risk increases with letrozole or exemestane versus TAM for EBC in PMW were reported in the Breast International Group 1-98 and Intergroup Exemestane studies, respectively. Earlier research has suggested that Zometa also might help stop breast cancer from spreading to the bones by making it harder for breast cancer cells to grow in bones and might help reduce the risk of the cancer coming back (recurrence) in women diagnosed with early-stage breast cancer. Although, the time of starting and the duration of administration of Zometa are still unanswered in need to future research. We will involve about 25 Patients of postmenopausal women who have ER/PR positive early breast cancer in each arm. The study is a two-arm comparative, prospective, interventional, and randomized study. All patients who are on oral daily letrozole (2.5 mg), will be randomly assigned to receive either immediate or delayed ZOL (4 mg via 15-min infusion every 6 months) for 24 months. Immediate-ZOL patients will receive ZOL immediately after randomization; delayed-ZOL patients will receive ZOL only if their T-score fall below -2.0, after a nontraumatic clinical fracture, or if an asymptomatic fracture will be detected by spinal X-ray at the 3- monthly assessment. All patients will receive daily supplements containing calcium (500 mg) and vitamin D (400–800 IU). Baseline bone mineral density and every 3 months will be done for the enrolled patients.
Type of trial RCT
Acronym (If the trial has an acronym then please provide)
Disease(s) or condition(s) being studied Cancer
Sub-Disease(s) or condition(s) being studied
Purpose of the trial Treatment: Drugs
Anticipated trial start date 30/12/2021
Actual trial start date 30/12/2021
Anticipated date of last follow up 30/12/2023
Actual Last follow-up date 30/12/2023
Anticipated target sample size (number of participants) 50
Actual target sample size (number of participants) 50
Recruitment status Active, not recruiting
Publication URL
Secondary Ids Issuing authority/Trial register
AUH Research Center Ethics Committee
STUDY DESIGN
Intervention assignment Allocation to intervention If randomised, describe how the allocation sequence was generated Describe how the allocation sequence/code was concealed from the person allocating the participants to the intervention arms Masking If masking / blinding was used
Parallel: different groups receive different interventions at same time during study Randomised Simple randomization using a randomization table created by a computer software program Allocation was determined by the holder of the sequence who is situated off site Open-label(Masking Not Used)
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Experimental Group Zoledronic acid We will involve about 25 Patients of postmenopausal women who have ER/PR positive early breast cancer in each arm. The study is a two-arm comparative, prospective, interventional, and randomized study. All patients who are on oral daily letrozole (2.5 mg), will be randomly assigned to receive either immediate or delayed ZOL (4 mg via 15-min infusion every 6 months) for 24 months. Immediate-ZOL patients will receive ZOL immediately after randomization; delayed-ZOL patients will receive ZOL only if their T-score fall below -2.0, after a nontraumatic clinical fracture, or if an asymptomatic fracture will be detected by spinal X-ray at the 3- monthly assessment. All patients will receive daily supplements containing calcium (500 mg) and vitamin D (400–800 IU). Baseline bone mineral density and every 3 months will be done for the enrolled patients. every 6 months) for 24 months. We will involve about 25 Patients of postmenopausal women who have ER/PR positive early breast cancer in each arm. The study is a two-arm comparative, prospective, interventional, and randomized study. All patients who are on oral daily letrozole (2.5 mg), will be randomly assigned to receive either immediate or delayed ZOL (4 mg via 15-min infusion every 6 months) for 24 months. Immediate-ZOL patients will receive ZOL immediately after randomization; delayed-ZOL patients will receive ZOL only if their T-score fall below -2.0, after a nontraumatic clinical fracture, or if an asymptomatic fracture will be detected by spinal X-ray at the 3- monthly assessment. All patients will receive daily supplements containing calcium (500 mg) and vitamin D (400–800 IU). Baseline bone mineral density and every 3 months will be done for the enrolled patients. 25
Control Group placebo no 24 months Delayed-ZOL arm patients will receive ZOL only if their T-score fall below -2.0, after a nontraumatic clinical fracture, or if an asymptomatic fracture will be detected by spinal X-ray at the 3- monthly assessment. All patients will receive daily supplements containing calcium (500 mg) and vitamin D (400–800 IU). Baseline bone mineral density and every 3 months will be done for the enrolled patients. 25 Placebo
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
1- Histologic evidence of ER/PR positive breast adenocarcinoma 2- Postmenopausal women. 3- Baseline LS and total hip BMD T-score > -2.0. 4- No prior treatment with denosumab or IV bisphosphonates is allowed. 5- No prior treatment with radiopharmaceuticals. 6- Not pregnant and not nursing. 7- Good dental health. 8- ECOG performance status 0-2. 9- Calculated creatinine clearance >= 30 mL/min. 10- Corrected serum calcium >= 8.0 mg/dL (2.00 mmol/L) and < 11.6 mg/dL (2.90 mmol/L) 1- Patients with dental problems. 2- Patients with impaired renal functions 3- Patients with osteopenia, or T- score is below -2.0 4- Patients with history of serious drug hypersensitivity or drug allergy. 80 and over: 80+ Year,Aged: 65+ Year(s),Middle Aged: 45 Year(s)-64 Year(s) 45 Year(s) 80 Year(s) Female
ETHICS APPROVAL
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 17/11/2021 AUH Research Center Ethics Committee
Ethics Committee Address
Street address City Postal code Country
Assuit University Hospital, Assuit, Egypt Assuit 1111 Egypt
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome The primary endpoint will be the percentage change in lumber spine (L2-L4) BMD at 12 months for immediate- versus delayed-ZOL patients. at 12 months for immediate- versus delayed-ZOL patients for 24 months
Secondary Outcome Secondary end points will include percentage change in total hip BMD at each assessment, fracture incidence, time to disease recurrence (local relapse or distant metastasis), DFS, and safety. 24 months
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
AUH Clinical Oncology Department, Assuit University Hospital, Assuit, Egypt Assuit 1111 Egypt
FUNDING SOURCES
Name of source Street address City Postal code Country
Mai Mohamed Hemmat Abdelfatah Abdelgelil Assuit Assuit 1111 Egypt
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor AUH Assuit Assuit 1111 Egypt Hospital
COLLABORATORS
Name Street address City Postal code Country
CONTACT PEOPLE
Role Name Email Phone Street address
Principal Investigator MAI ABDELGELIL maihemmat86@gmail.com 00201026556852 Assuit
City Postal code Country Position/Affiliation
Assuit 1111 Egypt ASSISTANT LECTURER OF CLINICAL ONCOLOGY AT ASSUIT UNIVERSITY HOSPITAL EGYPT
Role Name Email Phone Street address
Scientific Enquiries Samy Algezawy Samyalgiz@yahoo.com 002010296396 Assuit
City Postal code Country Position/Affiliation
Assuit 1111 Egypt prof. of clinical oncology at Assuit University Hospital
Role Name Email Phone Street address
Public Enquiries Rehab Farouk Rehabfar@yahoo.com 00201004435644 Assuit
City Postal code Country Position/Affiliation
Assuit 1111 Egypt prof. of clinical oncology at Assuit University Hospital
REPORTING
Share IPD Description Additional Document Types Sharing Time Frame Key Access Criteria
Yes After collecting patients data, we will analize and share it Study Protocol 24 months through a link
URL Results Available Results Summary Result Posting Date First Journal Publication Date
No
Result Upload 1: Result Upload 2: Result Upload 3: Result Upload 4: Result Upload 5:
Result URL Hyperlinks Link To Protocol
Result URL Hyperlinks
Changes to trial information