Neoplasms

Symptoms and General Pathology

All Conditions

Neoplasm Metastasis

Patients undergo CT scans. Additional images will be processed with virtual non-calcium (VNC) dual energy CT (DECT) information. Comparison will be made between images with and without addition of VNC.

virtual non-calcium dual-energy computed tomography

computed tomography

Naveen Subhas, MD

This clinical trial studies dual energy computed tomography (CT) in finding cancer that has spread from the original (primary) tumor to the bone (bone metastases) in patients with cancer. Diagnostic procedures, such as dual energy CT, may help find and diagnose bone metastases and may be more accurate compared to single energy CT alone.

PRIMARY OBJECTIVES:

I. Compare the accuracy of single energy CT (SECT) with virtual non-calcium (VNC) double energy CT (DECT) to standard SECT alone in the detection of metastatic bone lesions using positron emission tomography (PET)-CT as the reference standard.

OUTLINE:

Computed tomography (CT) scans are routinely used in the evaluation of oncologic patients for initial diagnosis and subsequent disease staging. Detection of bone metastasis on standard CT, however, is limited in sensitivity, particularly in case of osteolytic intramedullary lesions. Recent studies have shown the ability to detect bone marrow edema using CT with the use of a virtual non-calcium (VNC) dual energy CT (DECT) technique. Because bone marrow edema is similar in composition to intramedullary bone metastases (i.e. both are of soft tissue composition as opposed to calcium or fat), VNC DECT may also be helpful in the detection of bone marrow metastasis. Cancer patients obtaining a Positron Emission Tomography (PET) CT and a separate diagnostic CT scan as part of their routine clinical care will be enrolled into the study. The diagnostic CT scan will be performed on a DECT scanner and the images will be reconstructed as SECT images for routine clinical interpretation as well as VNC DECT images. The SECT images alone will be evaluated and scored, and then the VNC DECT images will be added to the SECT images for a second evaluation (consecutive reading session). Multiple readers blinded to the PET-CT findings for detection of bony metastatic disease will participate.

Researchers hypothesize the addition of VNC DECT to SECT will be more accurate in the detection of metastatic bone marrow lesions compared to SECT alone.

Dual Energy Computed Tomography (CT) in Finding Bone Metastases in Patients With Cancer

Evaluation of Bone Metastases With Dual Energy Computed Tomography (CT)

Number of lesions detected at the 46 designated locations at the time of the VNC DECT

Number of absent lesions from the 46 designated locations at the time of the VNC DECT

Each location will be correlated with PETCT which will serve as the reference standard.

Will be measured using nonparametric estimates of the area under the receiver operating characteristic (ROC) curve using methods for clustered data (i.e. multiple locations per patient). ROC area estimates will be constructed for each reader for both SECT alone and DECT as an adjunct to SECT. For each reader, the ROC areas of SECT and DECT plus SECT will be compared using a Wald test; a significance level of 0.05 will be used. Analysis of variance methods for multiple-reader ROC studies will be used. A 95% confidence interval for the difference in ROC areas will be constructed.

National Cancer Institute (NCI)

Case Comprehensive Cancer Center

Skin and Connective Tissue Diseases

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Heart and Blood Diseases

Blood and Lymph Conditions

Immune System Diseases

Rare Diseases

Breast Neoplasms

Prostatic Neoplasms

Carcinoma

Multiple Myeloma

Neoplasms, Plasma Cell

Adenocarcinoma

Recurrence

Pain

Neoplasms by Histologic Type

Hemostatic Disorders

Blood Coagulation Disorders

Vascular Diseases

Paraproteinemias

Blood Protein Disorders

Hematologic Diseases

Hemorrhagic Disorders

Lymphoproliferative Disorders

Immunoproliferative Disorders

Neoplasms, Glandular and Epithelial

Bone Density Conservation Agents

All Drugs and Chemicals

Zoledronic Acid

Patients receive zoledronic acid IV over at least 15 minutes every 4 weeks for up to 2 years in the absence of disease progression or unacceptable toxicity.

Patients receive zoledronic acid IV over at least 15 minutes every 12 weeks for up to 2 years in the absence of disease progression or unacceptable toxicity.

zoledronic acid

Andrew L. Himelstein, MD

This randomized phase III trial studies two different schedules of zoledronic acid to compare how well they work in reducing bone-related complications in patients with breast cancer, prostate cancer, or multiple myeloma that has spread to other places in the body and have bone involvement. Bone-related complications are a major cause of morbidity in patients with metastatic prostate cancer, breast cancer, and multiple myeloma. Zoledronic acid may stop the growth of cancer cells in the bone and may help relieve some of the symptoms caused by bone metastases. It is not yet known whether giving zoledronic acid more or less frequently is more effective in treating patients with metastatic cancer that has spread to the bone.

PRIMARY OBJECTIVES:

I. To determine whether every-12-week therapy with zoledronic acid is not inferior to every-4-week therapy for patients with metastatic breast cancer, metastatic prostate cancer, or multiple myeloma involving bone, as measured by the proportion who experience at least one skeletal related event within 24 months after randomization.

SECONDARY OBJECTIVES:

I. To compare pain scores (Brief Pain Inventory) of patients with metastatic breast cancer, metastatic prostate cancer, or myeloma involving bone receiving every 12 week dosing of zoledronic acid to those receiving every 4 week dosing.

II. To compare the functional status (Eastern Cooperative Oncology Group \[ECOG\] performance status) of patients with metastatic breast cancer, metastatic prostate cancer, or myeloma involving bone receiving every 12 week dosing of zoledronic acid to those receiving every 4 week dosing.

III. To compare the incidence of osteonecrosis of the jaw in patients with metastatic breast cancer, metastatic prostate cancer, or myeloma involving bone receiving every 12 week dosing of zoledronic acid to those receiving every 4 week dosing.

IV. To compare the incidence of renal dysfunction in patients with metastatic breast cancer, metastatic prostate cancer, or myeloma involving bone receiving every 12 week dosing of zoledronic acid to those receiving every 4 week dosing.

V. To compare the skeletal morbidity rate of these patients, defined as the number of skeletal-related events per year, of patients receiving every 12 week dosing to those receiving every 4 week dosing.

VI. To compare the suppression of serum markers of bone resorption of patients with metastatic breast cancer, metastatic prostate cancer, or myeloma involving bone receiving every 12 week dosing of zoledronic acid to those receiving every 4 week dosing.

VII. To determine whether every 12 week therapy with zoledronic acid is not inferior to every-4-week therapy for each subgroup of patients with either breast cancer, prostate cancer, or multiple myeloma, as measured by the proportion who experience at least one skeletal related event within 24 months after randomization.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive zoledronic acid intravenously (IV) over at least 15 minutes every 4 weeks for up to 2 years in the absence of disease progression or unacceptable toxicity.

ARM II: Patients receive zoledronic acid IV over at least 15 minutes every 12 weeks for up to 2 years in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 4 weeks for 2 years from registration.

Zoledronic Acid in Treating Patients With Metastatic Breast Cancer, Metastatic Prostate Cancer, or Multiple Myeloma With Bone Involvement

A Randomized, Phase III Study of Standard Dosing Versus Longer Dosing Interval of Zoledronic Acid in Metastatic Cancer

To determine whether every-12-week therapy with zoledronic acid is not inferior to every-4-week therapy for patients with metastatic breast cancer, metastatic prostate cancer, or multiple myeloma involving bone, as measured by the proportion of patients who would have experienced at least one skeletal related event within 24 months after randomization.

To compare pain scores (Brief Pain Inventory) of patients with metastatic breast cancer, metastatic prostate cancer, or myeloma involving bone receiving every 12 week dosing of zoledronic acid to those receiving every 4 week dosing. The change scores were evaluated in a general linear model with repeated measures for treatment effect and the time trend with patient-specific characteristics being adjusted for the mean interference score. Specifically the difference in score change per 4 weeks for Arm I using Arm II as the reference is reported. The score of the BPI questionnaire ranges from 0 being no pain to 10 being the most pain. The average score is reported for each arm below.

To compare functional status (ECOG performance status) of patients with metastatic breast cancer, metastatic prostate cancer, or myeloma involving bone receiving every 12 week dosing of zoledronic acid to those receiving every 4 week dosing. The change scores were evaluated in a general linear model with repeated measures for treatment effect and the time trend with patient-specific characteristics being adjusted. Specifically the difference in score change per 4 weeks for Arm I using Arm II as the reference is reported. ECOG performance status is a measurement of a patients disability ranging from 0, fully active and able to carry out all pre disease performance without restriction, to 5, dead. The average performance status is reported below by arm.

To compare the incidence of osteonecrosis of the jaw in patients with metastatic breast cancer, metastatic prostate cancer, or myeloma involving bone receiving every 12 week dosing of zoledronic acid to those receiving every 4 week dosing. The percentage of participants with osteonecrosis is reported here.

To compare the incidence of renal dysfunction of patients with metastatic breast cancer, metastatic prostate cancer, or myeloma involving bone receiving every 12 week dosing of zoledronic acid to those receiving every 4 week dosing. The percentage of patients with renal dysfunction, defined as grade 3 or grade 4 increased creatinine (Common Terminology Criteria for Adverse Events version 3.0), will be reported here.

To compare the skeletal morbidity rate, defined as the number of skeletal-related events per year, of patients receiving every 12 week dosing to those receiving every 4 week dosing.

To compare the suppression of serum markers of bone resorption of patients with metastatic breast cancer, metastatic prostate cancer, or myeloma involving bone receiving every 12 week dosing of zoledronic acid to those receiving every 4 week dosing. The number of patients with high \& low CTX values by arm will be reported here.

To determine whether every 12 week therapy with zoledronic acid is not inferior to every-4-week therapy for patients with breast cancer, as measured by the proportion who experience at least one skeletal related event within 24 months after randomization.

To determine whether every 12 week therapy with zoledronic acid is not inferior to every-4-week therapy for patients with prostate cancer, as measured by the proportion who experience at least one skeletal related event within 24 months after randomization.

To determine whether every 12 week therapy with zoledronic acid is not inferior to every-4-week therapy for patients with multiple myeloma, as measured by the proportion who experience at least one skeletal related event within 24 months after randomization.

Alliance for Clinical Trials in Oncology

Arm I (Zoledronic Acid Every 4 Weeks)

Arm II (Zoledronic Acid Every 12 Weeks)

Total

Age, Continuous

Sex: Female, Male

United States

Region of Enrollment

All baseline patients demographics were analyzed.

All patients that were eligible and completed treatment were analyzed.

Percentage of Participants With at Least One Skeletal-related Event (SRE) Within 2 Years After Randomization

1766 patients completed treatment and were analyzed.

Average Pain Intensity Score as Assessed by the Brief Pain Inventory (BPI) Questionnaire

Average ECOG Performance Status

Incidence of Osteonecrosis of the Jaw

1689 patients completed treatment and were analyzed.

Incidence of Renal Dysfunction

Skeletal Morbidity Rate

Low CTX (<0.415ng/ml)

High CTX (>0.415ng/ml)

Patients with Breast Cancer receive zoledronic acid IV over at least 15 minutes every 4 weeks for up to 2 years in the absence of disease progression or unacceptable toxicity.

Breast Cancer 4 Weeks

Breast Cancer 12 Weeks

266 breast cancer patients who were treated and included in this portion of the substudy.

Bone Turnover Assessed by Serum C-telopeptide (CTX) Levels (Breast Cancer)

820 patients completed treatment and were analyzed.

Proportion of Patients Having at Least One SRE Within 24 Months After Randomization for the Subgroups of Patients With Breast Cancer

Patients with Prostate Cancer receive zoledronic acid IV over at least 15 minutes every 4 weeks for up to 2 years in the absence of disease progression or unacceptable toxicity.

Prostate Cancer 4 Weeks

Patients with Prostate Cancer receive zoledronic acid IV over at least 15 minutes every 12 weeks for up to 2 years in the absence of disease progression or unacceptable toxicity.

Prostate Cancer 12 Weeks

660 patients completed treatment and were analyzed.

Proportion of Patients Having at Least One SRE Within 24 Months After Randomization for the Subgroups of Patients With Prostate Cancer

Multiple Myeloma 4 Weeks

Patients with Breast Cancer receive zoledronic acid IV over at least 15 minutes every 12 weeks for up to 2 years in the absence of disease progression or unacceptable toxicity.

Multiple Myeloma 12 Weeks

265 patient completed treatment and were analyzed.

Proportion of Patients Having at Least One SRE Within 24 Months After Randomization for the Subgroups of Patients With Multiple Myeloma

High CTX (>.0.415ng/ml)

207 prostate cancer patients who were treated and included in this portion of the substudy.

Bone Turnover Assessed by Serum C-telopeptide (CTX) Levels (Prostate Cancer)

74 multiple myeloma patients were treated and included in this portion of the substudy.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Dual Energy Computed Tomography (CT) in Finding Bone Metastases in Patients With Cancer	NCT02354326	Malignant Neopl... Metastatic Mali...	virtual non-cal... computed tomogr...	18 Years -	Case Comprehensive Cancer Center
Zoledronic Acid in Treating Patients With Metastatic Breast Cancer, Metastatic Prostate Cancer, or Multiple Myeloma With Bone Involvement	NCT00869206	Breast Adenocar... DS Stage I Plas... DS Stage II Pla... Metastatic Mali... Pain Musculoskeletal... Urinary Complic...	zoledronic acid	18 Years -	Alliance for Clinical Trials in Oncology
Zoledronic Acid in Treating Patients With Metastatic Breast Cancer, Metastatic Prostate Cancer, or Multiple Myeloma With Bone Involvement	NCT00869206	Breast Adenocar... DS Stage I Plas... DS Stage II Pla... Metastatic Mali... Pain Musculoskeletal... Urinary Complic...	zoledronic acid	18 Years -	Alliance for Clinical Trials in Oncology

Spots Global Cancer Trial Database for metastatic malignant neoplasm to the bone