Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Breast Neoplasms

Breast Diseases

Skin Diseases

All Drugs and Chemicals

Antineoplastic Agents

Vaccines

Fulvestrant

Estrogens

Aromatase Inhibitors

Progesterone

THERATOPE® vaccine

The purpose of this study is to examine the immunological response rate to administration of the THERATOPE® vaccine in women with stable metastatic breast cancer who are being treated with aromatase inhibitors or Faslodex® and who do not require chemotherapy.

Post-menopausal women on aromatase inhibitors or Faslodex® alone and pre-menopausal women on aromatase inhibitors plus luteinising hormone-releasing hormone (LH/RH)-agonist may be eligible to be enrolled.

Patients must not have had radiotherapy or major surgery within four (4) weeks prior to entering the study.

Information about the safety and tolerability of administration of the THERATOPE® vaccine will also be gathered during the course of the study.

Safety and Immunological Response Rate Study of THERATOPE® Vaccine in Metastatic Breast Cancer Patients

Open-Label, Phase II Trial of Immunological Response Rate, Safety, and Tolerability of THERATOPE® Vaccine in Subjects With Metastatic Breast Cancer Undergoing Treatment With Aromatase Inhibitors or Faslodex®

Oncothyreon Canada Inc.

Wounds and Injuries

Fractures, Bone

Menopause

Bone Density Conservation Agents

Herbal and Botanical

Tin Fluorides

Denosumab

Participants are post- menopausal with a breast cancer diagnosis who received at least 2 doses of denosumab, and then discontinued therapy, and discontinued Aromatase Inhibitors/AI prior to or within 6 months of stopping denosumab

Participants will be assessed at Timepoint 0 (last dose of denosumab injection) and then at 9,12,18 and 24 months following discontinuation of denosumab. The evaluation will include history and pain assessment for development of new fractures, weight and height measurement with BMI (body mass index) calculation, and blood work for bone turnover markers (including serum carboxy-terminal collagen crosslinks (CTX) in serum and bone specific alkaline phosphatase). Bone turn-over markers should be drawn in the morning, after at least 8 hours of fasting (water, black coffee and plain tea allowed).

Physical Evaluation

Dual-energy X-ray absorptiometry (DEXA) scans will be performed at the 12 months timepoint , and then at the 24 month timepoint.

Dual-energy X-ray absorptiometry scans

TBS is an innovative gray-level texture measurement that utilizes lumbar spine DEXA images to discriminate changes in bone microarchitecture. Specifically, TBS measures bone quality through tridimensional bone areas with different trabecular and microstructural characteristics. The combination of TBS microstructure evaluation with bone density measured by DEXA has been shown to be superior to either measurement alone in the assessment of fracture risk.

Trabecular Bone Score

Monica Fornier, MD

Azeez Farooki, MD

The purpose of this study to gather information about changes in the bones after stopping treatment with aromatase inhibitor/AI and denosumab. The study team will collect information from 5 standard clinic visits over the course of 24 months. The information will include information about participant health assessments, blood test results, and imaging results. After 24 months, participation in this study will be complete.

Observational Study of Bone Complications in People With Post-menopausal Breast Cancer Who Have Stopped Treatment With Denosumab and Aromatase Inhibitors

Post-menopausal Breast Cancer Patients Treated With Aromatase Inhibitors and Denosumab: An Observational Study to Assess Rebound Bone Loss and Insufficiency Fractures After Denosumab Discontinuation

Memorial Sloan Kettering Cancer Center supports the international committee of medical journal editors (ICMJE) and the ethical obligation of responsible sharing of data from clinical trials. The protocol summary, a statistical summary, and informed consent form will be made available on clinicaltrials.gov when required as a condition of Federal awards, other agreements supporting the research and/or as otherwise required. Requests for deidentified individual participant data can be made beginning 12 months after publication and for up to 36 months post publication. Deidentified individual participant data reported in the manuscript will be shared under the terms of a Data Use Agreement and may only be used for approved proposals. Requests may be made to: crdatashare@mskcc.org.

Evaluate changes in bone turnover markers at 12 months after the last dose of denosumab - serum carboxy-terminal collagen crosslinks (CTX)

Evaluate changes in bone turnover markers at 12 months after the last dose of denosumab - bone specific alkaline phosphatase (ALK)

Memorial Sloan Kettering Cancer Center

Calcium

Calcium, Dietary

Dual x-ray absorptiometry (DXA)

Baseline - genotyping Baseline, 6 months, and 12 months - markers of bone turnover and hormonal assays

Blood draw

Menopausal symptom questionnaire - baseline, 3 months, 6 months, 12 months

Cognitive tests - baseline, 6 months, 12 months

Depression assessment - baseline, 6 months, 12 months

Dietary calcium intake questionnaire - baseline

Questionnaire

Antonella Rastelli, MD

The primary objective of this 2-year pilot project is to test the hypothesis that skeletal response to aromatase inhibitors is determined by polymorphisms of the CYP19 gene.

A family history of osteoporosis will be noted. Data on the factors that affect estrogen exposure such as age at menarche, average number of periods per year during the reproductive years, number of years of birth control pill use, total number of pregnancies, number of pregnancies to term, months of lactation and age at menopause will be recorded. These data will be collected at baseline. Current medications and other medical problems will be recorded at baseline and during follow-up visits. New medical problems and new medications will be noted on follow-up.

Physical examination will be done at baseline and during follow-up visits. Body mass index calculated as weight (kg) divided by the square of the height (m2) will be obtained every visit. Height will be obtained using a standard stadiometer and weight will be taken using a standard weighing scale.

Dietary calcium and Vitamin D intake will be estimated from a 7-day dietary recall at baseline and adjusted to a daily intake of 1200-1500 mg of calcium per day. Vitamin D intake will also be adjusted to 800 IU per day.

Biochemical Analysis. Routine serum comprehensive metabolic profile (CMP) will be measured by standard autoanalyzer technique, serum 25-hydoxyvitamin D by double-antibody radioimmunoassay (Incstar Corp., Stillwater, Minnesota), and FSH by chemiluminescent assay (Bayer, NY) in those cases when the last menstrual period occurred less than 12 months before the signing of the informed consent. These measurements will be done through the Barnes-Jewish Hospital Laboratory. Serum estradiol will be measured by radioimmunoassay (Diagnostic Systems Laboratories Inc.), and sex hormone binding globulin by double antibody radioimmunoassay (Diagnostic Laboratories Inc). Serum estradiol measurements will be done at the Core Laboratory of the General Clinical Research Center (GCRC) of Washington University School of Medicine while the sex hormone binding globulin assay will be done at Dr. Villareal's laboratory. The inter- and intra-assay coefficients of variation for these assays are all \< 10%. In order to improve accuracy of the analysis the biochemical tests (except for 25-OH Vitamin D) will be performed at the end of the study and will be run by the same operator and plate (run in batch).

Bone Mineral Density (BMD) BMD of the total body, lumbar spine and the proximal left femur will be measured by dual energy X-ray absorptiometry (DEXA) using Hologic QDR 4500 (Hologic Inc., Waltham Ma, U.S.A.). Measurements will be done at month 0, 6 and 12 (see Visits and Testing Schedule). To guarantee the necessary flexibility for the patients who can not be seen at the exact date for the follow up a window of 1 month earlier and 2 months of late will be considered. BMD of the lumbar spine will be measured from L1 to L4. The non-dominant hip will be used for studies on the proximal femur. The main regions of interest on the proximal femur will be the total femur, femoral neck and femoral trochanter. The coefficient of variability for these repeated measurements in our institution is1.09% for the lumbar spine and 1.2% for the total femur in our center.

Bone Turnover Markers will be obtained at month 0, 6 and 12. We will follow a marker of bone resorption (urine cross-linked N- telopeptide of type I collagen \[urine NTx\] or, when a proper 24 hour urine collection is not done, serum cross-linked telopeptide of type I collagen \[serum CTx) will be analyzed) and one marker of bone formation (serum bone specific alkaline phosphatase {BSAP). Due to the diurnal pattern of bone markers, all serum specimens will be collected in the fasting state while urinary NTx will measured on 24-hour urine collection. These markers will be measured by ELISA at the Core laboratory for Clinical Studies at Washington University as follows: Urine NTX (Osteomark, Ostex International, Inc., Seattle, WA), serum CTX (serum crosslaps, Osteometer, Hawthorne, CA) and serum BSAP (Alkphase-B, Metra Biosystems, Inc., Mountain View, CA). Intra-assay coefficients of variations are in the range of 4-7% (32;33). In order to improve accuracy of the analysis biochemical tests will be performed at the end of the study and will be run by the same operator and plate (conducted in batch).

Vertebral Fracture Evaluation. We will evaluate vertebral fractures using the vertebral fracture assessment (VFA) method performed by the same DEXA machine used to measure the bone mineral density. Those patients whose VFA is suspicious for a fracture will undergo a lateral spine X-ray. Vertebral fractures will be identified by visual inspection of lateral spine radiographs of the thoracic and lumbar vertebrae, from T4 to L5. Interpretation of radiographs will be done by the PI, who is an endocrinologist specializing in bone disease and the Medical Director of the Bone Health Program in the Division of Bone and Mineral Diseases at Washington University School of Medicine. If the PI will have some doubts, she can easily ask the opinion from the bone radiologists at the Department of Radiology at Washington University School of Medicine.

Menopausal symptom evaluation. Symptoms related to menopause will be evaluated using a modified Leuven menopause questionnaire. This is a straightforward menopause-specific questionnaire which covers vasomotor, gynecologic, psychological, cognitive and somatic symptoms which was developed and validated in a previous study (Anti-Cancer Drugs 2004 15:753-760). The Leuven questionnaire includes definitions of each menopausal symptoms and rated as: 1 (no symptom), 2 (mild) up to 5 (intolerable). This questionnaire will be administered at month 0, 3, 6 and 12. This questionnaire will be administered during the patient visits at month 0, 6 and 12, and it will be sent by mail approximately two weeks prior to month 3. A phone call will also be made to the patients to prompt them to complete the questionnaire approximately at the time they should receive it by mail (month 3). Those who will fail to send the questionnaire within 1 week after the indicated dates will be contacted by phone. A log will be kept to document phone call attempts and dates of mailings to document persistence with compliance. A symptom score will be estimated for each participant. The number of symptomatic subject in each genotype will also be estimated.

Psychometric testing: In the current project we will assess the cognitive impairment using the mini mental state examination test (normal range of \> 72 for women \< 8 years of formal education and \> 76 for those who have \> 9 years of formal education) and attention and executive functions using Trail making tests A and B (the score is the number of seconds spent in connecting 25 numbered circles in sequential order \[trail A\] or the seconds spent in connecting numbered circles (1-13) alternately to letters of the alphabet (A-L) in sequential order \[Trail B\]. In both tests a maximum of 180 seconds is allowed). A fluency test will be performed asking to the subjects to name as many animals as they can during 1 minute. Additionally the Geriatric Depression Scale (GDS) will be performed in order to exclude and to assess eventual depression. This test implies 30 questions, each one corresponding to a score of 0 or 1. According to the final score a patient is classified normal with a score ranging from 0 to 9, mildly depressed if from 10 to 20, and severely depressed if the score is higher than 20. These tests will be administered during the patient visits at month 0, 6 and 12.

Rationale. To date, 4 polymorphisms of the aromatase gene have been associated with significant differences in BMD and fracture risk (16-18), age-related bone loss (18;29) a few of which have also been found to be associated with differences in breast cancer risk (30). Functional in-vitro analysis suggests an altered enzymatic activity in certain variants for this gene perhaps accounting for differences in the risk of breast cancer and osteoporosis. Variants with increased aromatase activity (18), as in those with higher number of TTTA repeats, have higher BMD but higher risk for breast cancer (30) possibly a consequence of higher estrogen levels. Because these variants have increased enzyme activity, it is possible that this select group of women will have increased sensitivity to aromatase inhibition and would experienced more bone loss than those with lower aromatase activity. On the contrary, it is also possible that women with these variant alleles will be relatively resistant to aromatase inhibition compared to variants with lower enzymatic activity and will continue to synthesize estrogen from precursors and, therefore, will not develop rapid bone loss. This proposal will address this important question by comparing the variants of the different polymorphisms described below.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Safety and Immunological Response Rate Study of THERATOPE® Vaccine in Metastatic Breast Cancer Patients	NCT00046371	Breast Neoplasm...	THERATOPE® vacc...	18 Years -	Oncothyreon Canada Inc.
Observational Study of Bone Complications in People With Post-menopausal Breast Cancer Who Have Stopped Treatment With Denosumab and Aromatase Inhibitors	NCT05590949	Breast Cancer	Physical Evalua... Dual-energy X-r... Trabecular Bone...	18 Years -	Memorial Sloan Kettering Cancer Center
Effect of Aromatase Inhibitors on Bones and Genes	NCT00603967	Breast Cancer Postmenopausal	Dual x-ray abso... Blood draw Questionnaire	40 Years -	Washington University School of Medicine
Observational Study of Bone Complications in People With Post-menopausal Breast Cancer Who Have Stopped Treatment With Denosumab and Aromatase Inhibitors	NCT05590949	Breast Cancer	Physical Evalua... Dual-energy X-r... Trabecular Bone...	18 Years -	Memorial Sloan Kettering Cancer Center
Effect of Aromatase Inhibitors on Bones and Genes	NCT00603967	Breast Cancer Postmenopausal	Dual x-ray abso... Blood draw Questionnaire	40 Years -	Washington University School of Medicine
Safety and Immunological Response Rate Study of THERATOPE® Vaccine in Metastatic Breast Cancer Patients	NCT00046371	Breast Neoplasm...	THERATOPE® vacc...	18 Years -	Oncothyreon Canada Inc.
Effect of Aromatase Inhibitors on Bones and Genes	NCT00603967	Breast Cancer Postmenopausal	Dual x-ray abso... Blood draw Questionnaire	40 Years -	Washington University School of Medicine

Spots Global Cancer Trial Database for aromatase

Every month we try and update this database with for aromatase 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 aromatase

Every month we try and update this database with for aromatase 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 aromatase 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.