Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

All Conditions

Skin and Connective Tissue Diseases

Musculoskeletal Diseases

Prostatic Neoplasms

Breast Neoplasms

Bone Resorption

Bone Diseases

Bone Neoplasms

Breast Diseases

Skin Diseases

Genital Neoplasms, Male

Urogenital Neoplasms

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Prostatic Diseases

Male Urogenital Diseases

Bone Density Conservation Agents

All Drugs and Chemicals

Antineoplastic Agents

Zoledronic Acid

Saracatinib

Enzyme Inhibitors

Zoledronic Acid 4 mg on Day 1 of the 4-week treatment period

AZD0530

Richard Finkelman, DDS, PhD

Meabe Aklilu, MD

The purpose of this study is to determine the effect of AZD0530 on subjects with breast cancer or prostate cancer with metastatic bone disease in comparison to zoledronic acid.

Study to Evaluate the Safety and Effects AZD0530 on Prostate and Breast Cancer Subjects With Metastatic Bone Disease

A Phase II, Randomised, Open-Label, Pilot Study to Evaluate the Safety and Effects on Bone Resorption of AZD0530 in Patients With Prostate Cancer or Breast Cancer With Metastatic Bone Disease.

Result at Week 4 minus result at baseline as a percentage of the result at baseline, based on log transformed data. Back transformation of the least squares (LS) mean.

Previous studies have shown that saracatinib reduces osteoclast function and bone resorption. Bone turnover, the combined result of bone formation and bone resorption, can be assessed in real time by measuring specific markers of bone turnover in serum and in urine. These markers were assessed in a study of patients with metastatic bone disease treated with saracatinib. Specific assays are available to quantitate these markers in serum and urine. In this study the effects of saracatinib on bone turnover were compared with the effects of zoledronic acid, a marketed drug known to inhibit bone resorption in cancer patients with bone metastatses.

AstraZeneca

safety set: AZD0530 175mg=68, Zoledronic acid 4mg=69

AZD0530 175 mg

Zoledronic Acid 4 mg

Total

Age Continuous

Sex: Female, Male

Non-compliant patients were excluded from the biomarker analysis, in order to accurately assess effects due to treatment. The compliance criteria did not apply to the zoledronic acid arm, which led to an imbalance in the number of subjects analysed.

Gerard Lynch

The number of participants analyzed reflected the number of paired serum samples per participant that yielded valid assay results, not the total number of participants or completers. The number of evaluable paired serum samples will therefore be a subset of the total number of participants.

Percentage Change From Baseline in Serum Beta C-terminal Cross-linking Telopeptide of Type I Collagen (betaCTX) at Week 4

Percentage Change From Baseline in Serum Bone-specific Alkaline Phosphatase (bALP) at Week 4

Percentage Change From Baseline in Serum Cross-linked C-terminal Telopeptide of Type I Collagen (ICTP) at Week 4

Percentage Change From Baseline in Serum N-terminal Propeptide of Type I Procollagen (PINP) at Week 4

Percentage Change From Baseline in Serum Tartrate-resistant Acid Phosphatase 5b (TRAP5b) at Week 4

Percentage Change From Baseline in Urine N-terminal Cross-linking Telopeptide of Type I Collagen Normalised to Creatinine (NTx/Cr) at Week 4

Percentage Change From Baseline in Urine Alpha-alpha C-terminal Cross-linking Telopeptide of Type I Collagen Normalised to Creatinine (aaCTx/Cr) at Week 4

Saracatinib: Area Under the Curve at Steady State (AUCss)

Saracatinib: Plasma Clearance at Steady State (CLss/F)

Saracatinib: Maximum Plasma Concentration at Steady State (Css,Max)

Saracatinib: Minimum Plasma Concentration at Steady State (Css,Min)

Saracatinib: Time to Cssmax (Tmax)

N-desmethyl Metabolite of Saracatinib: Area Under the Curve at Steady State (AUCss)

N-desmethyl Metabolite of Saracatinib: Maximum Plasma Concentration at Steady State (Css,Max)

N-desmethyl Metabolite of Saracatinib: Minimum Plasma Concentration at Steady State (Css,Min)

N-desmethyl Metabolite of Saracatinib: AUCss Metabolite to Parent Ratio

N-desmethyl Metabolite of Saracatinib: Time to Cssmax (Tmax)

Overall Study

Symptoms and General Pathology

Neoplasm Metastasis

Pain

Neoplastic Processes

* Patients will receive simulation, planning, quality assurance, and their first treatment in a single day using the STAT RT workflow.
* Patients will receive a total of 1-5 fractions of high dose palliative radiation therapy via TomoTherapy consisting of 5-10 Gray per fraction.
* Data will be collected to evaluate the effectiveness of our novel image co-registration techniques, CT-detector-based exit dose calculations, and infrared patient position monitoring. These novel techniques for image co-registration, radiation dose calculations, and patient position monitoring will not alter or replace standard of care techniques.

STAT RT planning and delivery workflow

Paul W Read, MD

The purpose of this research study is to evaluate the safety and effectiveness of an experimental workflow that may result in a faster way to plan and deliver radiation for the treatment of pain caused by metastatic bone tumors (tumors that originally came from another organ and have spread to bones causing pain) or multiple myeloma (a type of cancer that begins in white blood cells that produce antibodies).

The current standard of care radiation treatment planning and delivery takes 2 to 3 weeks from start to finish. The investigators have developed an experimental workflow: a radiation treatment planning and delivery workflow called "STAT RT" (STAT means "right away", and RT means radiation therapy). This experimental workflow may shorten the time it takes to plan and treat painful bone metastases to 1 week or less. All steps in this process will be performed within the current standard of care but in a shorter time frame to allow treatment to start sooner.

The investigators will evaluate effectiveness by requesting patients to complete pain and quality of life questionnaires before and after treatment. The investigators will also be collecting additional information from their treatments that will help us make future workflows even more efficient.

Background: Osseous metastatic disease causes significant pain, decreased functioning, and decreased quality of life. Progressive bone destruction can lead to pathologic fractures or spinal cord compression leading to orthopedic surgery, paralysis, and/or patients becoming bedridden. Opioids can alleviate pain but have neurologic and gastrointestinal side effects that further decrease quality of life. Radiation therapy can effectively reduce pain and opioid use and prevent further bone destruction, however, its use is limited because the current workflow frequently requires one week for planning and two weeks for delivery. Additionally, typical palliative radiation plans for osseous metastases lack conformality of dose to the tumor volume, and therefore, result in radiation-induced toxicity to large volumes of adjacent normal tissue. Recent software and hardware advancements provide the opportunity to revolutionize the palliative treatment of osseous metastases. The investigators propose to investigate a novel TomoTherapy-based workflow, called STAT RT, which includes same day CT simulation, treatment planning, and quality assurance measurements coupled with highly conformal treatment delivery for patients with osseous metastases in a pilot clinical trial.

Objective: The overall goal of this STAT RT proposal is to develop a more rapid, convenient, and effective palliative radiation approach for patients with osseous metastases that is less toxic and less expensive than current treatment regimens. The investigators have already optimized the conformality of TomoTherapy-based radiation doses for osseous metastases, and the investigators have developed a STAT RT workflow that condenses standard of care simulation, planning, quality assurance, and treatment delivery into 5-6 hours. Additional optimization and integration of new radiation therapy computing processes will allow for real time simulation, planning, and delivery via a novel Scan-Plan-Treat STAT RT workflow that will ultimately require only 30 minutes. In this study the investigators will evaluate the effectiveness of the current STAT RT workflow, and the investigators will investigate techniques for further optimization that will be needed to create a 30 minute Scan-Plan-Treat STAT RT workflow.

Primary Specific Aim/ Hypothesis: The investigators will quantify the time for pain relief, amount of pain relief, opioid use reduction, functional scores, quality of life, and satisfaction of patients treated with STAT RT for osseous metastases. The investigators hypothesize that these patients will have rapid and significant pain relief, improved quality of life, and high patient satisfaction.

Secondary Specific Aim/ Hypothesis: The investigators will optimize the integration of commercially available and in-development software to develop the Scan-Plan-Treat STAT RT workflow. Specifically, the investigators will A) optimize rigid and deformable co-registration of pre-contoured diagnostic image sets to MVCT simulation scans and compare the accuracy to the same pre-contoured diagnostic image sets co-registered to kilovoltage CT (kVCT) simulation images and then kVCT simulation to MVCT scan co-registration, B) optimize CT-detector-based exit dose measurement algorithms for quality assurance and compare to standard of care phantom-based quality assurance, C) optimize the accuracy of an in-house real time infrared tracking system for intrafractional patient position monitoring to ensure accurate patient treatment. The investigators hypothesize that these new components will provide effective and efficient methods for treatment planning, quality assurance, and patient position monitoring that can be used in a future 30 minute Scan-Plan-Treat STAT RT workflow.

Study design: The investigators will recruit 30 cancer patients with 1-3 painful osseous metastatic lesions (target sites) who are candidates for palliative radiation therapy. Patients will receive 1-5 fractions of 5-8 Gray (Gy) (minimum biologic effective dose of 25 Gy) of conformal radiation therapy delivered to the target sites via the Helical TomoTherapy system using the STAT RT workflow. Data will be collected to evaluate the effectiveness of our novel image co-registration techniques, CT-detector-based exit dose calculations, and infrared patient position monitoring. These novel techniques for image co-registration, radiation dose calculations, and patient position monitoring will not alter or replace standard of care techniques. Using validated surveys the investigators will record patient pain, analgesic use, function, quality of life, and patient satisfaction prior to treatment and at 1 week, 4 weeks, 8 weeks, 12 weeks, 6 months, and 12 months after therapy. Radiation-induced treatment related toxicities will be captured during treatment and at the above time points.

Rapid Radiation Therapy for Painful Osseous Metastatic Disease

Phase II Pilot Single Arm Prospective Clinical Trial of Rapid Institution of Helical TomoTherapy-based Radiation Therapy for Patients With Painful Osseous Metastatic Disease

The Brief Pain Inventory (BPI) and Oral Morphine Equivalent Doses (OMED) were used to categorize the number of participants who had a Complete Response (no pain), Partial Response (pain reduction), Stable Pain (no change in pain), and Pain Progression at 12 months after receiving treatment via the STAT RT workflow.

Toxicity will be assessed by CTCAE Version 4.0 Toxicity will be assessed up to 12 months after treatment.

The patient's quality of life function will be assessed using the Brief Pain Inventory (BPI) 1 week post treatment. Min-'0'/'Does not interfere'; Max-'10'/'Completely interferes.' ; Worst Pain Score: 1-4=Mild Pain, Worst Pain Score 5-6=Moderate Pain. Worst Pain Score 7-10=Severe Pain.

The patient's quality of life and function will be assessed using the Brief Pain Inventory (BPI) 4 weeks post treatment. Min-'0'/'Does not interfere'; Max-'10'/'Completely interferes.' ; Worst Pain Score: 1-4=Mild Pain, Worst Pain Score 5-6=Moderate Pain. Worst Pain Score 7-10=Severe Pain.

The patient's quality of life function will be assessed using the Brief Pain Inventory (BPI) 8 weeks post treatment. Min-'0'/'Does not interfere'; Max-'10'/'Completely interferes.' ; Worst Pain Score: 1-4=Mild Pain, Worst Pain Score 5-6=Moderate Pain. Worst Pain Score 7-10=Severe Pain.

The patient's quality of life and function will be assessed using the Brief Pain Inventory (BPI) 12 weeks post treatment. Min-'0'/'Does not interfere'; Max-'10'/'Completely interferes.' ; Worst Pain Score: 1-4=Mild Pain, Worst Pain Score 5-6=Moderate Pain. Worst Pain Score 7-10=Severe Pain.

the patient's quality of life and function will be assessed using the Brief Pain Inventory (BPI) 6 months post treatment. Min-'0'/'Does not interfere'; Max-'10'/'Completely interferes.' ; Worst Pain Score: 1-4=Mild Pain, Worst Pain Score 5-6=Moderate Pain. Worst Pain Score 7-10=Severe Pain.

The patient's quality of life and function will be assessed using the Brief Pain Inventory (BPI) 12 months post treatment. Min-'0'/'Does not interfere'; Max-'10'/'Completely interferes.' ; Worst Pain Score: 1-4=Mild Pain, Worst Pain Score 5-6=Moderate Pain. Worst Pain Score 7-10=Severe Pain.

The patient's quality of life and function will be assessed using the Functional Assessment of Cancer Therapy (FACT-BP) survey 1 week post treatment. Min-'0'/'Not at all' and Maximum 4+ 'Very much.' Items scored per FACT_BP Scoring guidelines version 4; Score Range 0-60; The higher the score, the better QOL function.

The patient's quality of life and function will be assessed using the Functional Assessment of Cancer Therapy (FACT-BP) survey 4 weeks post treatment. Min-'0'/'Not at all' and Maximum 4+ 'Very much.' Items scored per FACT_BP Scoring guidelines version 4; Score Range 0-60; The higher the score, the better QOL function.

The patient's quality of life and function will be assessed using the Functional Assessment of Cancer Therapy (FACT-BP) survey 8 weeks post treatment. Min-'0'/'Not at all' and Maximum 4+ 'Very much.' Items scored per FACT_BP Scoring guidelines version 4; Score Range 0-60; The higher the score, the better QOL function.

The patient's quality of life and function will be assessed using the Functional Assessment of Cancer Therapy (FACT-BP) survey 12 weeks post treatment. Min-'0'/'Not at all' and Maximum 4+ 'Very much.' Items scored per FACT_BP Scoring guidelines version 4; Score Range 0-60; The higher the score, the better QOL function.

The patient's quality of life and function will be assessed using the Functional Assessment of Cancer Therapy (FACT-BP) survey 6 months post treatment. Min-'0'/'Not at all' and Maximum 4+ 'Very much.' Items scored per FACT_BP Scoring guidelines version 4; Score Range 0-60; The higher the score, the better QOL function.

The patient's quality of life and function will be assessed using the Functional Assessment of Cancer Therapy (FACT-BP) survey 12 months post treatment. Min-'0'/'Not at all' and Maximum 4+ 'Very much.' Items scored per FACT_BP Scoring guidelines version 4; Score Range 0-60; The higher the score, the better QOL function.

The patient's quality of life and function will be assessed using the Functional Assessment of Cancer Therapy (FACT-G) survey within 1 week post treatment. Min-'0'/'Not at All'; Max-'4'/'Very Much'; 28 questions total are broken into 4 categories scoring ranges 0-24 or 0-28 (depending on the category). Total score is ranged 0-108; Higher the score, the better quality of life (QOL).

The patient's quality of life and function will be assessed using the Functional Assessment of Cancer Therapy (FACT-G) survey within 4 weeks post treatment. Min-'0'/'Not at All'; Max-'4'/'Very Much'; 28 questions total are broken into 4 categories scoring ranges 0-24 or 0-28 (depending on the category). Total score is ranged 0-108; Higher the score, the better quality of life (QOL).

The patient's quality of life and function will be assessed using the Functional Assessment of Cancer Therapy (FACT-G) survey within 8 weeks post treatment. Min-'0'/'Not at All'; Max-'4'/'Very Much'; 28 questions total are broken into 4 categories scoring ranges 0-24 or 0-28 (depending on the category). Total score is ranged 0-108; Higher the score, the better quality of life (QOL).

The patient's quality of life and function will be assessed using the Functional Assessment of Cancer Therapy (FACT-G) survey within 12 weeks post treatment. Min-'0'/'Not at All'; Max-'4'/'Very Much'; 28 questions total are broken into 4 categories scoring ranges 0-24 or 0-28 (depending on the category). Total score is ranged 0-108; Higher the score, the better quality of life (QOL).

The patient's quality of life and function will be assessed using the Functional Assessment of Cancer Therapy (FACT-G) survey within 6 months post treatment. Min-'0'/'Not at All'; Max-'4'/'Very Much'; 28 questions total are broken into 4 categories scoring ranges 0-24 or 0-28 (depending on the category). Total score is ranged 0-108; Higher the score, the better quality of life (QOL).

The patient's quality of life and function will be assessed using the Functional Assessment of Cancer Therapy (FACT-G) survey within 12 months post treatment. Min-'0'/'Not at All'; Max-'4'/'Very Much'; 28 questions total are broken into 4 categories scoring ranges 0-24 or 0-28 (depending on the category). Total score is ranged 0-108; Higher the score, the better quality of life (QOL).

Estimate patient satisfaction with the STAT RT workflow using Functional Assessment of Chronic Illness Therapy-Bone Treatment Convenience and Satisfaction Questionnaire (FACIT-TS-BTCSQ). Satisfaction will be assessed within 1 week post treatment. Min-'0'/'Not at All'; Max-'4'/'Very Much'; FACIT-TS-BTCSQ Baseline Scoring Guidelines (Version 4) includes sub of individual items multiplied by 13 to give score; The higher the score, the higher the quality of life (QOL).

Estimate patient satisfaction with the STAT RT workflow using Functional Assessment of Chronic Illness Therapy-Bone Treatment Convenience and Satisfaction Questionnaire (FACIT-TS-BTCSQ). Satisfaction will be assessed within 4 weeks post treatment. Min-'0'/'Not at All'; Max-'4'/'Very Much'; FACIT-TS-BTCSQ Baseline Scoring Guidelines (Version 4) includes sub of individual items multiplied by 13 to give score; The higher the score, the higher the quality of life (QOL).

Estimate patient satisfaction with the STAT RT workflow using Functional Assessment of Chronic Illness Therapy-Bone Treatment Convenience and Satisfaction Questionnaire (FACIT-TS-BTCSQ). Satisfaction will be assessed within 8 weeks post treatment. Min-'0'/'Not at All'; Max-'4'/'Very Much'; FACIT-TS-BTCSQ Baseline Scoring Guidelines (Version 4) includes sub of individual items multiplied by 13 to give score; The higher the score, the higher the quality of life (QOL).

Estimate patient satisfaction with the STAT RT workflow using Functional Assessment of Chronic Illness Therapy-Bone Treatment Convenience and Satisfaction Questionnaire (FACIT-TS-BTCSQ). Satisfaction will be assessed within 12 weeks post treatment. Min-'0'/'Not at All'; Max-'4'/'Very Much'; FACIT-TS-BTCSQ Baseline Scoring Guidelines (Version 4) includes sub of individual items multiplied by 13 to give score; The higher the score, the higher the quality of life (QOL).

Estimate patient satisfaction with the STAT RT workflow using Functional Assessment of Chronic Illness Therapy-Bone Treatment Convenience and Satisfaction Questionnaire (FACIT-TS-BTCSQ). Satisfaction will be assessed within 6 months post treatment. Min-'0'/'Not at All'; Max-'4'/'Very Much'; FACIT-TS-BTCSQ Baseline Scoring Guidelines (Version 4) includes sub of individual items multiplied by 13 to give score; The higher the score, the higher the quality of life (QOL).

Estimate patient satisfaction with the STAT RT workflow using Functional Assessment of Chronic Illness Therapy-Bone Treatment Convenience and Satisfaction Questionnaire (FACIT-TS-BTCSQ). Satisfaction will be assessed within 12 months post treatment. Min-'0'/'Not at All'; Max-'4'/'Very Much'; FACIT-TS-BTCSQ Baseline Scoring Guidelines (Version 4) includes sub of individual items multiplied by 13 to give score; The higher the score, the higher the quality of life (QOL).

University of Virginia

Study Chair

Per protocol, treatment may continue for 2 to 5 fractions depending of the clinical situation. Most subjects will receive treatments for less than 1 week, however, all treatments must be completed within 21 days. AEs will be collected for 30 days following the last treatment.

single arm

STAT RT planning and delivery workflow: -Patients will receive simulation, planning, quality assurance, and their first treatment in a single day using the STAT RT workflow.

* Patients will receive a total of 1-5 fractions of high dose palliative radiation therapy via TomoTherapy consisting of 5-10 Gray per fraction.
* Data will be collected to evaluate the effectiveness of our novel image co-registration techniques, CT-detector-based exit dose calculations, and infrared patient position monitoring. These novel techniques for image co-registration, radiation dose calculations, and patient position monitoring will not alter or replace standard of care techniques.

STAT RT Planning and Delivery Workflow

Age, Categorical

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Dr. Paul Read

The Brief Pain Inventory (BPI) and Oral Morphine Equivalent Doses (OMED) were used to categorize the number of participants who had a Complete Response (no pain), Partial Response (pain reduction), or Stable Pain (no change in pain) at 12 months after receiving treatment via the STAT RT workflow.

Number of Participants With a Complete Response, Partial Response, or Stable Pain After Receiving Treatment Via the STAT RT Workflow at 12-months

Number of subjects with Grade 3 or higher adverse events within 12 months after initial treatment. No serious AEs reported; all AEs were grade 2 or less. Additional AE details found in published article.

Number of Participants With Treatment Toxicity

Number of Participants With an Improved Quality of Life Function Score at 1 Week Post Treatment

Number of Participants With an Improved Quality of Life Function Score at 4 Weeks After Initial Treatment

Number of Participants With an Improved Quality of Life Function Score at 8 Weeks After Initial Treatment

Number of Participants With an Improved Quality of Life Function Score at 12 Weeks Post Initial Treatment

Number of Participants With an Improved Quality of Life Function Score at 6 Months After Initial Treatment

Number of Participants With an Improved Quality of Life Function Score at 12 Months After Initial Treatment

Patient Quality of Life and Function (FACT-BP) Assessed 1 Week Post Initial Treatment

Patient Quality of Life and Function (FACT-BP) Assessed 4 Weeks After Initial Treatment

Patient Quality of Life and Function (FACT-BP) Assessed 8 Weeks After Initial Treatment

Patient Quality of Life and Function (FACT-BP) Assessed 12 Weeks After Initial Treatment

Patient Quality of Life and Function (FACT-BP) Assessed 6 Months After Initial Treatment

Patient Quality of Life and Function (FACT-BP) Assessed 12 Months After Initial Treatment

Patient Quality of Life and Function (FACT-G) Assessed 1 Week After Initial Treatment

Patient Quality of Life and Function (FACT-G) Assessed 4 Weeks After Initial Treatment

Patient Quality of Life and Function (FACT-G) Assessed 8 Weeks After Initial Treatment

Patient Quality of Life and Function (FACT-G) Assessed 12 Weeks After Initial Treatment

Patient Quality of Life and Function (FACT-G) Assessed 6 Months After Initial Treatment

Patient Quality of Life and Function (FACT-G) Assessed 12 Months After Initial Treatment

Patient Quality of Life and Function (FACIT-TS-BTCSQ) Assessed 1 Week After Initial Treatment

Patient Quality of Life and Function (FACIT-TS-BTCSQ) Assessed 4 Weeks After Initial Treatment

Patient Quality of Life and Function (FACIT-TS-BTCSQ) Assessed 8 Weeks After Initial Treatment

Patient Quality of Life and Function (FACIT-TS-BTCSQ) Assessed 12 Weeks After Initial Treatment

Patient Quality of Life and Function (FACIT-TS-BTCSQ) Assessed 6 Months After Initial Treatment

Patient Quality of Life and Function (FACIT-TS-BTCSQ) Assessed 12 Months After Initial Treatment

Denosumab

Pamidronate

1 dose of denosumab every 4 weeks for 2 doses, followed by 1 dose of pamidronate every 4 weeks for 2 doses.

1 dose of pamidronate every 4 weeks for 2 doses, followed by 1 dose of denosumab every 4 weeks for 2 doses.

Treatment Group A - 120 mg SC dose every 4 weeks at Day 1 and week 5 Treatment Group B - 120 mg SC dose every 4 weeks at Week 9 and Week 13

denosumab

Treatment Group A - 90 mg IV dose every 4 weeks at Week 9 and Week 13 Treatment Group B - 90 mg IV dose every 4 weeks at Day 1 and Week 5

pamidronate

This study will estimate the total time for the preparation and administration of denosumab and the total time for the preparation and administration of pamidronate.

Evaluate Time Associated With the Preparation & Administration of Denosumab/Pamidronate in Patients With Solid Tumors and Metastatic Bone Disease

An Open-Label, Multicentre Trial to Evaluate the Time Associated With the Preparation and Administration of Denosumab and Pamidronate in Subjects With Solid Tumors and Metastatic Bone Disease in Canada

Amgen

Blood and Lymph Conditions

Bone Marrow Diseases

Hematologic Diseases

Roxanne Gal, PhD

Helena M. Verkooijen, MD PhD

Helena M. Verkooijen, MD, PhD

Bone metastases are frequent distant manifestations of cancer, with pain as a common and devastating consequence. The primary treatment for painful bone metastases, external beam radiation therapy, is moderately effective: about 60% of patients who undergo conventional radiotherapy experience (partial) pain relief. Several factors associated with treatment failure have been identified, but no attempts have been made to collapse these factors into a clinically useful prediction tool to predict treatment response. In addition, to aid in therapy selection based on expected survival time, development of survival models is essential. Finally, we need innovative treatments as alternatives or additive to standard treatment options to improve quality of life (QoL). For these reasons, we set up the PRESENT cohort study, recruiting patients at the departments of radiation oncology and orthopedic surgery.

We aim to provide detailed information about clinical data, create an infrastructure for efficient, fast and pragmatic evaluation and implementation of innovative interventions, as well as development of accurate new prediction tools.

The PRESENT cohort is set up according to the 'cohort multiple Randomised Controlled Trial' design. The basis of this design is a prospective cohort of patients with bone metastases, receiving care as usual, who give informed consent for cohort participation. At the UMC Utrecht, patients are furthermore asked for informed consent to be randomized in future RCTs conducted within the cohort. Patients are informed that they will be offered the experimental intervention if they are randomly selected. They are also informed that they otherwise might serve as controls without being notified and that their data can be used in a trial context. For each patient in the cohort, clinical and patient-reported outcomes are captured at baseline and at regular intervals during follow-up. Within this cohort, multiple RCTs can be conducted. For this purpose, eligible patients who have provided the consent required for them to participate in an RCT within the cohort are identified. From this subcohort, a random selection of patients will be invited to undergo the experimental intervention. Eligible participants who were not randomly selected receive standard care, are not informed about the experimental intervention and serve as controls. Outcomes in this control group are compared with the outcomes of those who were offered the experimental intervention, in order to estimate the effect of the experimental intervention versus usual care. Within the cohort, the same process can be repeated for trials of other interventions.

Prospective Evaluation of Interventional Studies on Bone Metastases - the PRESENT Cohort

Current enrolment approaches 2000 patients. Investigators are encouraged to request data after consulting the study team.

Grade 3 and 4 side effects occurring during or up to 3 months after radiotherapy will be registered according to the Common Terminology Criteria for Adverse Events (CTCAE version 4). The following side effects will be registered: Nausea; Vomiting; Diarrhoea; Pain flare.

Reintervention (reirradiation, surgery, other); Development of neurological symptoms; Development of pathologic fracture

Survival of participating patients will be recorded using the follow up questionnaires (returned by family members) or are derived from the Municipal Personal Records Database (in Dutch: Gemeentelijke Basisadministratie, GBA).

UMC Utrecht

Prof. dr.

Participants will receive a single IV infusion of ZA 4 mg at the start of treatment and a once-daily odanacatib matching placebo tablet for 4 weeks.

Participants will receive a once-daily odanacatib 5 mg tablet for 4 weeks and a single IV infusion of ZA matching placebo at the start of treatment.

Single ZA 4 mg IV infusion at the start of treatment

Once-daily odanacatib 5 mg tablet for 4 weeks

Odanacatib

Once-daily odanacatib matching placebo for 4 weeks

Odanacatib matching placebo

Single IV infusion of ZA matching placebo given at the start of treatment

ZA matching placebo

Medical Monitor

This is a 4-week study to examine the effects of a new experimental medication on women with breast cancer and established bone metastases. This study will enroll approximately 45 women. The primary hypotheses are: (1) odanacatib will result in a substantial suppression of urinary N-telopeptide of type I collagen (u-NTx) similar to that achieved with an intravenous (IV) infusion of zoledronic acid (ZA) over 4 weeks of treatment; and (2) odanacatib (MK-0822) will be safe and well tolerated during 4 weeks of treatment.

A Study to Examine the Effects of an Experimental Drug on Women With Breast Cancer and Metastatic Bone Disease (MBD)(0822-016)(COMPLETED)

A Phase II Study to Assess the Safety, Tolerability, and Efficacy of MK-0822 (Cathepsin-K Inhibitor) in the Treatment of Women With Breast Cancer and Established Bone Metastases (MBD)

https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf

u-NTx is a biochemical index of bone resorption. Participants provided urine specimens on Day 1 (baseline) and at Week 4 for measurement of u-NTx.

An AE is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a study drug, whether or not it is considered related to the study drug.

u-DPD is a biochemical marker of bone resorption. Participants provided urine specimens on Day 1 (baseline) and Week 4 for measurement of u-DPD.

Merck Sharp & Dohme LLC

All randomized participants who took at least one dose of study drug

Participants received a single IV infusion of ZA 4 mg at the start of treatment and a once-daily odanacatib matching placebo tablet for 4 weeks.

Single IV Infusion of ZA 4 mg

Participants received a once-daily odanacatib 5 mg tablet for 4 weeks and a single IV infusion of ZA matching placebo at the start of treatment.

Once-daily Odanacatib 5 mg

Age, Continuous

Senior Vice President, Global Clinical Development

All randomized participants who took at least one dose of study drug and had available u-NTx data for Baseline and Week 4

Percentage Change From Baseline in Urinary N-telopeptide of Type I Collagen (u-NTx) at Week 4

Number of Participants Who Experienced an Adverse Event (AE)

Number of Participants Who Discontinued Treatment Due to an AE

All randomized participants who took at least one dose of study drug and had available u-DPD data for Baseline and Week 4

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Study to Evaluate the Safety and Effects AZD0530 on Prostate and Breast Cancer Subjects With Metastatic Bone Disease	NCT00558272	Breast Cancer Prostate Cancer Bone Neoplasms	AZD0530 Zoledronic Acid	18 Years -	AstraZeneca
Rapid Radiation Therapy for Painful Osseous Metastatic Disease	NCT01391234	Bone Metastases	STAT RT plannin...	18 Years -	University of Virginia
Evaluate Time Associated With the Preparation & Administration of Denosumab/Pamidronate in Patients With Solid Tumors and Metastatic Bone Disease	NCT02101164	Solid Tumor Metastatic Bone...	denosumab pamidronate	18 Years -	Amgen
Prospective Evaluation of Interventional Studies on Bone Metastases - the PRESENT Cohort	NCT02356497	Bone Metastases		18 Years -	UMC Utrecht
A Study to Examine the Effects of an Experimental Drug on Women With Breast Cancer and Metastatic Bone Disease (MBD)(0822-016)(COMPLETED)	NCT00399802	Breast Cancer Metastatic Bone...	ZA Odanacatib Odanacatib matc... ZA matching pla...	18 Years -	Merck Sharp & Dohme LLC
Study to Evaluate the Safety and Effects AZD0530 on Prostate and Breast Cancer Subjects With Metastatic Bone Disease	NCT00558272	Breast Cancer Prostate Cancer Bone Neoplasms	AZD0530 Zoledronic Acid	18 Years -	AstraZeneca
Study to Evaluate the Safety and Effects AZD0530 on Prostate and Breast Cancer Subjects With Metastatic Bone Disease	NCT00558272	Breast Cancer Prostate Cancer Bone Neoplasms	AZD0530 Zoledronic Acid	18 Years -	AstraZeneca
Palliative UNConventional Hypofractionation Trial for Metastatic Bone Disease	NCT05115331	Metastatic Bone...	Experimental Ra... Conventional Ra...	18 Years -	University of Cincinnati
Study to Evaluate the Safety and Effects AZD0530 on Prostate and Breast Cancer Subjects With Metastatic Bone Disease	NCT00558272	Breast Cancer Prostate Cancer Bone Neoplasms	AZD0530 Zoledronic Acid	18 Years -	AstraZeneca
Fully Constrained Acetabular Liner vs. Dual Mobility Hip Joint in the Surgical Treatment of Metastatic Bone Disease of the Hip	NCT05461313	Metastatic Canc...	Constrained Lin... Dual Mobility	18 Years -	Rigshospitalet, Denmark

Spots Global Cancer Trial Database for metastatic bone disease