Neoplasms

Heart and Blood Diseases

Blood and Lymph Conditions

Immune System Diseases

All Conditions

Musculoskeletal Diseases

Symptoms and General Pathology

Rare Diseases

Multiple Myeloma

Neoplasms, Plasma Cell

Osteonecrosis

Bone Diseases

Osteolysis

Neoplasms by Histologic Type

Hemostatic Disorders

Blood Coagulation Disorders

Vascular Diseases

Paraproteinemias

Blood Protein Disorders

Hematologic Diseases

Hemorrhagic Disorders

Lymphoproliferative Disorders

Immunoproliferative Disorders

Bone Density Conservation Agents

All Drugs and Chemicals

Zoledronic Acid

treatment with zoledronic acid for 4 years

treatment with zoledronic acid withheld after two years

Zoledronic acid will be given to all participants for two years. Then patients will be randomized to A receive 2 more years of treatment or B stop treatment.

Zoledronic acid

Thomas LunD, MD Ph.D.

Main hypothesis: Patients who continue zoledronic acid after year 2 have longer time until progression in bone disease compared to patients who stop treatment after two years?

Secondary hypothesis: Serum will bone markers increase prior to progression in bone disease in the individual patient?

Secondary hypothesis: Low-dose CT will detect more cases of osteolytic bone disease in Multiple Myeloma compared to conventional radiography

Newly diagnosed myeloma patients will be followed for 4 years. The first two years they will be treated with zoledronic acid monthly. At year 2 they will be randomized to A continue treatment for 2 more years or B stop treatment. The primary outcome of the study will be time to progressive bone disease from year 2 and onward.

Serum bone markers will be measured throughout the study. In patients who experience progressive bone disease, development of bone markers prior to the radiological progression will be investigated to see the if it could have been predicted with the use of serum markers

During the four year period patients will have low-dose CT superior and conventional radiography made at predefined time points. The secondary outcome of the study is to compare the sensitivity of the two modalities

Prolonged Protection From Bone Disease in Multiple Myeloma

Magnolia Study Prolonged Protection From Bone Disease in Multiple Myeloma. An Open Label Phase 3 Multicenter International Randomised Trial

Patients will have low-dose CT and conventional x-ray made at predefined time points to compare the sensitivity between the two modalities

After two years of zoledronic acid treatment patients will be randomized to A continue treatment B stop treatment.

Development in bone markers prior to progression in osteolytic lesions will be investigated

Thomas Lund

MD Ph.D.

Skin and Connective Tissue Diseases

Breast Neoplasms

Hypersensitivity

Breast Diseases

Skin Diseases

Antineoplastic Agents

Gastrointestinal Agents

Tamoxifen

Letrozole

Lactitol

Aromatase Inhibitors

Enzyme Inhibitors

Estrogens

Estrogen Antagonists

Estrogen Receptor Antagonists

Hormones

Hormone Antagonists

Antineoplastic Agents, Hormonal

Estrogen Receptor Modulators

Selective Estrogen Receptor Modulators

2.5 mg once daily (q.d.)orally for 5 years

20 mg Tamoxifen once daily (q.d.) orally for 2 years followed by Letrozole 2.5 mg q.d. orally for 3 years.

2.5 mg tablets and supplied in bottles with 6-monthly supplies.

20 mg tablets in bottles as 6-monthly supplies (supplied to Novartis as Tamofen from Schering Oy, Subsidiary of Schering AG, Pansiontie 47, FIN-2010 Turku, Finland)

Novartis

Estrogen is known to be a regulator of bone and lipid metabolism. Letrozole is a potent inhibitor of estrogen synthesis.

This study evaluated the effects of letrozole and tamoxifen on bone and lipid metabolism in postmenopausal women with resected, receptor positive early breast cancer.

A Study to Evaluate the Effect of Letrozole and Tamoxifen on Bone and Lipids in Postmenopausal Women With Breast Cancer

Lumbar spine (L2-L4) BMD measurements by dual energy X-ray absorptiometry (DXA) were performed after surgery and within 2 weeks prior to randomization and repeated every 6 months for the first 2 years and annually thereafter until 5 years after enrollment. The primary scanning site was the lumbar spine (L2 to L4) and the secondary scanning site was the total hip. All DXA scans were evaluated by a central reader.

Lumbar spine (L2-L4)BMD measurements by dual energy X-ray absorptiometry (DXA) were performed after surgery and within 2 weeks prior to randomization and repeated every 6 months for the first 2 years and annually thereafter until 5 years after enrollment. The primary scanning site was the lumbar spine (L2 to L4) and the secondary scanning site was the total hip. All DXA scans were evaluated by a central reader.

Total hip BMD measurements by dual energy X-ray absorptiometry (DXA) were performed after surgery and within 2 weeks prior to randomization and repeated every 6 months for the first 2 years and annually thereafter until 5 years after enrollment. All DXA scans were evaluated by a central reader.

Bone turnover markers (fasting serum procollagen-I extension peptide \[P1NP\], C-telopeptide \[CTX\], skeletal bone-specific alkaline phosphatase \[BSAP, N-telopeptide \[NTX\]) were measured at baseline/screening and at each visit thereafter. A central laboratory was used to analyze the samples. The analysis of bone markers was based on analysis of variance of the regression slopes calculated for each individual patient and each bone marker over time. In the following summary, only the median treatment group percent change from baseline (and range) at 5 years is presented for each bone marker.

Serum lipid profile (fasting serum cholesterol \[total, HDL and calculated LDL\], triglycerides, and lipoprotein \[a\]) were measured at baseline/screening and at each visit thereafter. A central laboratory was used to analyze the samples. The analysis of serum lipids was on the treatment group median percent change from baseline (and range) at 5 years.

Serum lipid profile (fasting serum cholesterol \[total, HDL and calculated LDL\], triglycerides, and lipoprotein \[a\]) were measured at baseline/screening and at each visit thereafter. A central laboratory was used to analyze the samples. Numbers are not additive, as patients could be included in multiple rows.

Disease-free survival was defined as the interval between randomization and earliest confirmed event of loco-regional recurrence, distant metastases, invasive contralateral breast cancer, or death from any cause.

Overall survival was measured from date of randomization to date of death.

Danish Breast Cancer Cooperative Group

University of Sheffield

Novartis Pharmaceuticals

2.5 mg once daily q.d. orally for 5 years

Tam-Let

Tamoxifen 20 mg once daily (q.d.) orally for 2 years followed by Letrozole 2.5 mg q.d. orally for 3 years.

Total

Age, Continuous

Sex: Female, Male

The study was designed to investigate the effects of letrozole compared with tamoxifen for 2 years on BMD spine (L2-L4). The study was too small to investigate the comparative efficacy of treatments on disease-free survival or on overall survival.

The safety population consisted of only patients who took randomized therapy for at least one day. The number of patients in each treatment arm who had completed 2 years of the study and had centrally assessed measurements of lumbar spine or total hip BMD.

Percent Change From Baseline of Bone Mineral Density of the Lumbar Spine (L2-l4)

The safety population consisted of only patients who took randomized therapy for at least one day. The analysis at 5 years included all patients enrolled and who had centrally assessed measurements of lumbar spine and/or total hip BMD.

Percent Change From Baseline of Bone Mineral Density of the Lumbar Spine

The safety population consisted of only patients who took randomized therapy for at least one day. The analysis of BMD at 5 years included all patients enrolled with centrally assessed measurements of total hip BMD.

Percent Change From Baseline of Bone Mineral Density (BMD) of Total Hip

Procollagen-I (PINP) (n=86, 78)

Bone Specific alkaline Phosphatase (n=87,78)

C-telopeptide (CTX) (n=88, 78)

N-telopeptide (NTX) (n=-88, 77)

The safety population consisted of only patients who took randomized therapy for at least one day. During different time points, participants with observations at that time point were included in the analysis. The analysis of bone markers over time consisted of patients with measurements of specific markers at each time point.

Median Percent Change From Baseline of Serum Markers of Bone Turnover

Total Cholesterol (n=91, 82)

LDL Cholesterol (n=91, 82)

HDL Cholesterol (n=91, 82)

The safety population consisted of only patients who took randomized therapy for at least one day. During different time points, participants with observations at that time point were included in the analysis.

Percentage Change From Baseline in Serum Lipids at 5 Years

Patients with one or more change

≥8 mmol/L total (T) cholesterol

≥7 mmol/L T.choles. & ≥1 risk for cardiac disease

≥6 mmol/L T. choles. & ≥2 risk for cardiac disease

The safety population consisted of only patients who took randomized therapy for at least one day. The number of patients with pre-defined clinically relevant changes in serum lipids over the course of 5 years in each treatment arm is presented.

Number of Participants With Clinically Relevant Changes From Baseline in Cholesterol

Analysis of disease-free survival was based on the ITT principle, with all enrolled (and randomized) patients included. The Kaplan-Meier product-limit approach was used.

Time to Disease Recurrence or Death

All randomized patients constituted the ITT Population, unless withdrawal of consent occurred after randomization but before the start of study treatment assigned.

Time to Overall Survival Events

Overall Study

Sclerosteosis

Diphosphonates

Patients treated with intravenous bisphosphonate until 12 months in routine care

collected 10 mL of blood and 15 mL of urine every 2 months until 12 months

Blood and urine collection

Laurent Frenzel, MD

Hélène MOREL

Laurent FRENZEL, MD

The aim of this study is looking at the Kinetics of bone turnover markers (C-terminal telopeptides of type I collagene (CTX), amino-terminal telopeptide of type 1 collagen (NTX), Dickkopf-1 (DKK-1) and Sclerostin (SOST)) in serum and urine until 12 months in Patients with Multiple Myeloma Treated With intravenous bisphosphonates in routine care.

Study of 4 Bone Turnover Markers in Patients With Multiple Myeloma Treated With Intravenous Bisphosphonate in Routine Care

Assessment of 4 Bone Turnover Markers (C-terminal Telopeptides of Type I Collagene (CTX), Amino-terminal Telopeptide of Type 1 Collagen (NTX), Dickkopf-1 (DKK-1) and Sclerostin (SOST)) in Multiple Myeloma Patients Treated With Intravenous Bisphosphonate

bone turnover markers include: C-terminal telopeptides of type I collagene (CTX) in serum, amino-terminal telopeptide of type 1 collagen (NTX) in urine, Dickkopf-1 (DKK-1) and Sclerostin (SOST) in plasma

To study the relationship between doses and bone turnover markers

Intergroupe Francophone du Myelome

Assistance Publique - Hôpitaux de Paris

Bone Marrow Neoplasms

Bortezomib

bortezomib (Velcade) 1.6 mg/m² bolus injection on Days 1, 8, 15 and 22 every 5 weeks for 4 cycles

Each cycle will consist of 5 weeks treatment. Subjects in the treatment group will receive: Velcade® 1.6 mg/m2 as an intravenous bolus injection on Days 1, 8, 15, and 22 of each cycle followed by a 13-day rest period (Days 23 to 35) Cycle will be repeated on Day 36. Subjects in the treatment group will receive up to 4 treatment cycles, unless they experience either unacceptable toxicity or if the subject requests to withdraw from the study.

bortezomib

Janssen-Cilag International NV Clinical Trial

The purpose of this study is to assess the effect of bortezomib on myeloma-related bone disease, analyzing bone mineral density (BMD) in patients with Multiple Myeloma (MMY) who have received high dose chemotherapy and autologous stem cell transplantation for primary treatment of MMY (single- or double-transplant). Eligible patients will be randomized (study treatment assigned by chance like flipping a coin) to either bortezomib or observation alone. Patients in the bortezomib arm will receive treatment of bortezomib for a total of 4 cycles. All subjects will be followed for a total of 24 months after randomization.

This is a randomized, open-label (all people involved know the identity of the intervention), multicenter, multi-country parallel group study (each group of patients will be treated at the same time) in patients with Multiple Myeloma (MMY) who have received high dose chemotherapy and autologous stem cell transplantation for primary treatment of MMY (single- or double-transplant). The purpose of the study is to assess the effect of bortezomib on myeloma-related bone disease by analyzing bone mineral density. Approximately 80% of patients with MMY may experience myeloma-related bone disease. Myeloma-related bone disease may cause skeletal complications, including bone pain, bone lesions, abnormal fractures and super-elevated calcium concentrations in the blood. This study is investigating the safety and efficacy of an experimental drug, bortezomib, to consolidate the response to the primary treatment compared to no such consolidation treatment. The analyses in this study will be exploratory in nature, since the study will not address any pre-defined statements but is designed to generate valid hypotheses on safety and efficacy issues. Bortezomib is currently marketed for the treatment of different types of cancer including MMY. Bortezomib has been shown to promote bone formation and increase the number of bone-regenerating cells in preliminary studies. In the present study, the effect of bortezomib on bone formation will be assessed by dual energy x-ray absorptiometry (DXA) measuring bone mineral density, which is a measure for the quality of the bone structures. Several bone markers will be measured on serum samples. Bone markers are indicators of the bone activity. Patients will be evaluated for eligibility within a 14-day screening period, after providing written informed consent. Eligible patients will then be randomised to either bortezomib or observation alone. Baseline efficacy and safety assessments should be available on Cycle 1 Day 1 prior to administration of study medication. Randomization will be stratified by bisphosphonate treatment (use or not) at baseline and age (65 years or more versus less than 65 years). The treatment period is defined as the time the patient is actively receiving study treatment. Patients in the bortezomib arm will receive treatment of bortezomib for a total of 4 cycles or until start of alternative MMY treatment if earlier. Each cycle will consist of 5 weeks treatment. Subjects in the treatment group will receive bortezomib 1.6 mg/m2 on Days 1, 8, 15, and 22 of each cycle followed by a 13-day rest period (Days 23 to 35). Bisphosphonate therapy can be administered as medically indicated and according to local practice. Patients are to attend study center visits on Days 1, 8, 15, and 22 of each treatment cycle or at Days 1, 36, 71, and 106 in the observation arm and at end of treatment (EOT) Visit. During these visits, different evaluations will be conducted to follow treatment safety: symptom directed physical examination, vital signs and laboratory tests. In addition, at Day 1 of Cycle 3 (prior to dosing) or Day 71 in the observation arm, patients will be assessed for disease progression or relapse by measurements of M-protein in serum and urine. If needed, absence of M-protein in serum and urine will be confirmed by immunofixation. Additional evaluations may be performed to document patient's clinical status and ability to tolerate additional therapy as clinically indicated. All patients will be followed for a total of 24 months since baseline. After end of the treatment phase, there will be a long-term follow-up period with visits at 4, 6, 12 and 18 months after the EOT Visit. In case the patient started alternative MMY treatment before completing the 18 months of follow-up, study assessments will stop, except for QoL assessments, which are to be continued up to 18 months of follow-up, and for a long-term follow-up for survival, which will be collected every 6 months by either a telephone call or a visit to the study site. The follow-up for survival will continue for all patients until the last patient has completed follow-up. In addition to scheduled visits, patients may have additional visits as clinically indicated. Every patient who was randomized should enter the long-term follow-up phase. Assessment of progressive disease (PD) or relapse from complete response (CR) should be performed according to the International Myeloma Working Group (IMWG) 2009 criteria. Changes in serum and urine M-protein (monoclonal paraprotein) levels will be confirmed by immunofixation in patients without measurable serum and urine M-protein levels. Karnofsky performance status will also be assessed. Safety will be assessed by monitoring of adverse events, physical examination (including neurological/peripheral neurological examinations), vital signs measurements and clinical laboratory tests. A total of two exploratory analyses will be performed for the present study: The first analysis (main analysis) will be presented after completion of the EOT Visit (24-weeks data). The second analysis will be the analysis at the end of the study on 18 months follow-up data. Patients in the bortezomib arm will receive treatment of bortezomib 1.6 mg/m² as a bolus infusion on Days 1, 8, 15, and 22 every 5 weeks for a total of 4 cycles

Velcade Consolidation Bone Study

A Phase 2, Multicentre, Randomised, Open-Label, Parallel Group Study to Evaluate the Effect of VELCADE on Myeloma Related Bone Disease

Change from baseline in bone mineral density (BMD) will be assessed by dual energy x-ray absorptiometry scans at baseline and the EOT visit

Change from baseline in bone mineral density (BMD) will be assessed by dual energy x-ray absorptiometry scans at baseline and the end of treatment EOT visit

The Progression-Free Survival (PFS) was assessed as median number of months from baseline until the first documented sign of disease progression (increase in disease; radiographic, clinical, or both) or death due to any cause, whichever occurred earlier.

Bone markers (carboxyterminal telopeptide of type I collagen (ICTP), osteocalcin (Oc) and bone-specific alkaline phosphatase (BAP) was measured on serum samples.

Change from Baseline in Biochemical Bone Markers: CTX-I was assessed

Bone markers Dickkopf homolog 1 (DKK-1) was measured on serum samples.

Number of patients with skeletal-related events (i.e. pathological fracture (vertebral, non-vertebral, combined), radiotherapy, spinal cord compression, orthopaedic surgery, hypercalcaemia) occurring over 24 months study period

Appearance of new bone lesions assessed by skeletal survey compared to baseline

T score is used to calculate bone mineral density (calcium and other types of minerals) in an area of the bone. T score is the number of standard deviations above or below the mean for a healthy 30 year old adult of the same sex and ethnicity as a participant. This score is calculated from participant's age, gender and race and skeletal site. T score has a mean of '50' and a standard deviation of '10'. T score lower than its mean indicate low bone mineral density.

The Karnofsky performance status is a way to quantify cancer patients' general well-being and activities of daily life and runs from 100 to 0, where 100 is "perfect" health and 0 is death.

Overall survival defined as time from first treatment of MMY, i.e. day of first dose of induction therapy for MMY to date of death

Subjects were asked to rate their general state of health on a Visual analog scale (in millimeter \[mm\]) ranging from 0 (worst state of health) to 100 (best conceivable state of health) mm.

Tumor response was assessed as VGPR based on IMWG response criteria if, a) serum/urine M protein detectable by immunofixation but not on electrophoresis or; b) greater than or equal to 90% reduction in serum M protein plus urine M protein level less than 100 milligram/24 hour. CR=normal free light chain (FLC) ratio and absence of phenotypically aberrant plasma cells (PC) in bone marrow with a minimum of 3000 total PC analyzed by multiparametric flow cytometry; Complete response (CR) negative immunofixation on the serum and urine and, disappearance of any soft tissue plasmocytomas and \<5% plasma cells in bone marrow.

Tumor response was assessed as SD based on IMWG response criteria as not meeting criteria for CR, VGPR, PR, or progressive disease; PD as Increase of \>=25% from lowest response level in any one or more of the following: serum M protein (absolute increase \>=0.5 g/dl)c or urine M protein (absolute increase \>=200 mg/24 h); or serum/urine M protein unmeasurable: difference between involved and uninvolved free light chain (FLC) levels; absolute increase \>10 mg/dL; or % bone marrow plasma cells: absolute value \>=10% or definite development of new bone lesions or soft tissue plasmocytomas or definite increase in the size of existing bone lesions or soft tissue plasmocytomas; or development of hypercalcemia attributed solely to the plasma cell proliferative disorder.

Tumor response was assessed as PR based on IMWG response criteria as \>=50% reduction of serum and reduction in 24-h urinary M protein by \>=90% or to \<200 mg/24 h; or serum/urine M protein unmeasurable:\>=50% decrease in the difference between involved and uninvolved FLC levels; or serum/urine M protein and FLC assay unmeasurable: \>=50% reduction in plasma cells provided baseline bone marrow plasma cell percentage was \>=30%; or plus if present at baseline: \>=50% reduction in size of soft tissue plasmocytomas.

Janssen-Cilag International NV

Non-treated Control

EMEA Medical Affairs Director

ITT analysis:13 patients in the bortezomib group and 14 patients in the non-treated control group did not have values at the 2 timepoints to allow calculation of the parameter

Change From Baseline in Bone Mineral Density (BMD) in the Spine at End of Treatment (EOT)

Femur neck

Femur total

ITT analysis:8 patients in the bortezomib group and 8 patients in the non-treated control group did not have values at the 2 timepoints to allow calculation of the parameter

Change From Baseline in Bone Mineral Density (BMD) in the Femur at End of Treatment

Full Analysis Set (FAS) included all the randomized subjects who were eligible for efficacy analysis, that is, excluding subjects who did not have baseline and/or post-baseline data.

Progression Free Survival

ICTP (n= 44, 42)

Osteocalcin (44, 42)

BAP (42, 40)

FAS was used for analysis. "N" (number of subjects analyzed) signifies the subjects evaluable this measure and n=number pf participants analysed for this outcome measure at specific time point. Missing data was imputed by last observation carried forward (LOCF) method.

Change From Baseline in Biochemical Bone Markers:Carboxyterminal Telopeptide of Type I Collagen (ICTP), Osteocalcin, Bone-specific Alkaline Phosphatase (BAP)

Change From Baseline in Biochemical Bone Markers: Carboxyterminal Collagen Crosslinks (CTX-I)

Change From Baseline in Biochemical Bone Markers: Dickkopf Homolog 1 (DKK-1)

FAS included all the randomized subjects who were eligible for efficacy analysis, that is, excluding subjects who did not have baseline and/or post-baseline data. "N" (number of subjects analyzed) signifies the subjects evaluable this measure.

Number of Patients With Skeletal Events

Data could not be summarised statistically due to insufficient data at End of treatment.

Appearance of New Bone Lesions Compared to Baseline

FAS included all the randomized subjects who were eligible for efficacy analysis, that is, excluding subjects who did not have baseline and/or post-baseline data. "N" (number of subjects analyzed) signifies the subjects evaluable this measure. Missing data was imputed by last observation carried forward (LOCF) method.

Change From Baseline in Spine T-score

Screening

Follow-up

Karnofsky Performance Status

Overall Survival

FAS included all the randomized subjects who were eligible for efficacy analysis, that is, excluding subjects who did not have baseline and/or post-baseline data. Missing data was imputed by last observation carried forward (LOCF) method.

Change From Baseline in Quality of Life Assessed by Euro Quality of Life (EQ-5D)

Tumor Response: Percentage of Participants With Very Good Partial Response (VGPR) or Stringent Complete Response (sCR) or Complete Response (CR) Based on International Myeloma Working Group (IMWG) Response Criteria

Tumor Response: Percentage of Participants With Stable Disease (SD) or Progressive Disease (PD) Based on International Myeloma Working Group (IMWG) Response Criteria

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Prolonged Protection From Bone Disease in Multiple Myeloma	NCT02286830	Multiple Myelom...	Zoledronic acid	18 Years -	Odense University Hospital
A Study to Evaluate the Effect of Letrozole and Tamoxifen on Bone and Lipids in Postmenopausal Women With Breast Cancer	NCT00171704	Hormone Sensiti...	Letrozole Tamoxifen	50 Years -	Novartis
A Study to Evaluate the Effect of Letrozole and Tamoxifen on Bone and Lipids in Postmenopausal Women With Breast Cancer	NCT00171704	Hormone Sensiti...	Letrozole Tamoxifen	50 Years -	Novartis
Prolonged Protection From Bone Disease in Multiple Myeloma	NCT02286830	Multiple Myelom...	Zoledronic acid	18 Years -	Odense University Hospital
Study of 4 Bone Turnover Markers in Patients With Multiple Myeloma Treated With Intravenous Bisphosphonate in Routine Care	NCT04111809	Multiple Myelom...	Blood and urine...	65 Years - 75 Years	Assistance Publique - Hôpitaux de Paris
A Study to Evaluate the Effect of Letrozole and Tamoxifen on Bone and Lipids in Postmenopausal Women With Breast Cancer	NCT00171704	Hormone Sensiti...	Letrozole Tamoxifen	50 Years -	Novartis
Velcade Consolidation Bone Study	NCT01286077	Multiple Myelom...	bortezomib	18 Years -	Janssen-Cilag International NV
Prolonged Protection From Bone Disease in Multiple Myeloma	NCT02286830	Multiple Myelom...	Zoledronic acid	18 Years -	Odense University Hospital

Spots Global Cancer Trial Database for bone markers

Every month we try and update this database with for bone markers 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.