Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

All Conditions

Symptoms and General Pathology

Prostatic Neoplasms

Adenocarcinoma

Neoplasm Metastasis

Genital Neoplasms, Male

Urogenital Neoplasms

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Prostatic Diseases

Male Urogenital Diseases

All Drugs and Chemicals

Bone Density Conservation Agents

Antineoplastic Agents

Androgens

Zoledronic Acid

Atrasentan

Endothelin A Receptor Antagonists

Endothelin Receptor Antagonists

Zoledronic Acid (Zometa)

Matthew Smith, MD, PhD

The main purpose of this study is to look at the effects (good or bad) that Atrasentan given alone and Atrasentan given with Zometa has on levels of bone formation and bone destruction in men with prostate cancer that has spread to the bones.

* Patients will be randomized to either receive Atrasentan alone or Atrasentan plus Zometa.
* Patients receiving Atrasentan alone will receive this drug in pill form once daily for 12 weeks. Patients will have a physical exam, blood work, and a urine sample performed once every other week during the first four weeks of medication administration. After those two initial visits, they will return to the clinic once every 4 weeks to have the same tests repeated. A bone scan and abdominal-pelvic CT Scan will be done every 12 weeks.
* After the patient has been taking Atrasentan for 12 weeks, if the disease has not progressed, they will begin combination treatment of Atrasentan and Zometa.
* Patients receiving Atrasentan plus Zometa, receive Zometa intravenously and then immediately start Atrasentan orally once daily as long as they remain on the study. Patients will return to the clinic twice over the first 4 weeks (once every other week) to have a physical exam, blood work and urine test performed. After these two initial visits, they will return to the clinic once every 4 weeks to have the tests repeated and to receive another treatment of zometa. A bone scan and an abdominal-pelvic CT Scan will be done once every 12 weeks.
* Patients participation in this study will last as long as the disease does not progress and they are not experiencing any serious side effects.

Atrasentan and Zometa for Men With Prostate Cancer Metastatic to Bone

Atrasentan and Zometa for Men With Androgen Independent Prostate Cancer Metastatic to Bone: A Randomized Pilot Study

Dana-Farber Cancer Institute

Brigham and Women's Hospital

Abbott

Massachusetts General Hospital

Matthew R. Smith, MD, PhD

Heart and Blood Diseases

Blood and Lymph Conditions

Immune System Diseases

Musculoskeletal Diseases

Rare Diseases

Multiple Myeloma

Neoplasms, Plasma Cell

Pain

Bone Diseases

Neoplasms by Histologic Type

Hemostatic Disorders

Blood Coagulation Disorders

Vascular Diseases

Paraproteinemias

Blood Protein Disorders

Hematologic Diseases

Hemorrhagic Disorders

Lymphoproliferative Disorders

Immunoproliferative Disorders

Anti-Inflammatory Agents

Antiemetics

Gastrointestinal Agents

Dexamethasone

Bortezomib

Dexamethasone acetate

Glucocorticoids

Hormones

Hormone Antagonists

Antineoplastic Agents, Hormonal

For this study, Velcade will be administered at the standard dose of 1.3 mg/m2, iv, bolus, on days 1, 4, 8 and 11 of a 21-day cycle.

Dexamethasone will be administered at a dose of 12 mg/m2 p.o., on days 1-2, 4-5, 8-9 and 11-12 of the same cycle.

Zoledronic acid will be administered at a dose of 4 mg, iv (15-minute infusion), every 28 days for up to 8 cycles, and then every 28 days for the next 18 months

1.3 mg/m2, iv, bolus, on days 1, 4, 8 and 11 of a 21-day cycle for up to 8 chemotherapy cycles

4 mg, iv, at a 15 min infusion, Day 1 of every cycle for up to 8 cycles, and then every 28 days for the next 18 months

12 mg/m2 p.o. on days 1-2, 4-5, 8-9 and 11-12 of a 21-day cycle for up to 8 chemotherapy cycles

Meletios- Athanasios Dimopoulos, Professor

The aim of this study is to evaluate the effect of bortezomib in combination with dexamethasone and zoledronic acid on bone mineral density (BMD) and skeletal related events (SREs) in Patients with Multiple Myeloma who Have Relapsed after 1-3 Prior Lines of Therapy

Multiple Myeloma represents a malignant proliferation of plasma cells derived from a single clone. The most common symptom in myeloma, affecting more than 70% of patients at diagnosis, is bone pain. The pain usually involves the back and ribs, and is precipitated by movement. Bone fractures are commonly seen in myeloma patients and may present with persistent localized pain.

VELCADE (bortezomib) is a proteasome inhibitor used for the treatment of multiple myeloma.

VELCADE seems to be the first agent to combine significant anti-myeloma activity and beneficial effects on bone remodeling. Thus, it appears to be a very promising tool for the treatment of myeloma patients.

In this study, a regimen consisting of bortezomib/dexamethasone/zoledronic acid will be used. The rationale for using this regimen is that:

* VELCADE (bortezomib) is indicated for the treatment of relapsed myeloma patients participating in the study and it has also a beneficial effect on biochemical markers of bone formation.
* In phase II studies, the addition of dexamethasone in patients with a suboptimal response to bortezomib alone improved efficacy in relapsed or refractory multiple myeloma patients, without increasing adverse events. Therefore, in this study, the addition of dexamethasone aims at providing the optimal therapy for participating myeloma patients.
* Zoledronic acid, the most potent i.v. bisphosphonate, is used because of its established effect on reducing skeletal related events in patients with multiple myeloma due to its inhibitory effect on osteoclastic bone resorption.

Dosages and timing of dosages are based on current recommendations and guidelines for the treatment of myeloma patients who Have Relapsed after 1-3 Prior Lines of Therapy.

Effect of Combination of Bortezomib/Dexamethasone/Zoledronic Acid on Bone Disease in Patients With Multiple Myeloma Relapsed After 1-3 Prior Lines of Therapy

A Prospective, Multicenter, Non-comparative, Open-label, Phase II Study to Evaluate the Effects of the Combination of Bortezomib/Dexamethasone/Zoledronic Acid on Bone Mineral Density, Bone Metabolism, Radiographically-detected Osteolytic Bone Lesions, Skeletal-related Events and Bone Pain in Patients With Multiple Myeloma Who Have Relapsed After 1-3 Prior Lines of Therapy

BMD of the lumbar spine (L1-L4, anteroposterior view) and femoral neck (FN) was measured by dual energy X-ray absorptiometry (DXA) using a Hologic QDR-1000 scanner on day 21 of cycle 4 (day 84)

BMD of the lumbar spine (L1-L4, anteroposterior view) and femoral neck (FN) was measured by Dual Energy X-Absorptiometry scan (DEXA-scan) using a Hologic QDR-1000 scanner on day 21 of cycle 8 (day 168)

Bone remodelling was studied by the measurement of the following serum indices on day 21 of cycle 4 (day 84) using an enzyme-linked immunosorbent assay (ELISA): i) bone resorption marker C-terminal cross-linking telopeptide of collagen type I (CTX) and ii) bone formation markers \[osteocalcin (OC)\].

Bone remodelling was studied by the measurement of the following serum indices on day 21 of cycle 8 (day 168) using an enzyme-linked immunosorbent assay (ELISA): i) bone resorption marker C-terminal cross-linking telopeptide of collagen type I (CTX) and ii) bone formation marker \[osteocalcin (OC)\].

Bone pain was measured with the use of the Visual Analogue Scale on day 21 of cycle 4 (day 84).

Bone pain was measured with the use of the Visual Analogue Scale. The visual analogue scale or visual analog scale (VAS) is a psychometric response scale which can be used in questionnaires. It is a measurement instrument for subjective characteristics or attitudes that cannot be directly measured.

The VAS for Bone Pain was constructed as follows:

None Mild Moderate Severe Worst possible 1,2 3,4 5,6 7,8 9,10 Lower values are considered to be of a better outcome, higher values are considered to be of a worst outcome.

Bone pain was measured with the use of the Visual Analogue Scale on day 21 of cycle 8 (day 168).

Bone pain was measured with the use of the Visual Analogue Scale. The visual analogue scale or visual analog scale (VAS) is a psychometric response scale which can be used in questionnaires. It is a measurement instrument for subjective characteristics or attitudes that cannot be directly measured.

The VAS for Bone Pain was constructed as follows:

None Mild Moderate Severe Worst possible 1,2 3,4 5,6 7,8 9,10 Lower values are considered to be of a better outcome, higher values are considered to be of a worst outcome.

Skeletal survey was measured using conventional radiography \[imaging of the whole skeleton (skull, cervical spine, thoracic spine, lumbar spine, pelvis, humeri, femoral bones)\] on day 21 of cycle 8 (day 168)

Skeletal survey was measured using conventional radiography \[imaging of the whole skeleton (skull, cervical spine, thoracic spine, lumbar spine, pelvis, humeri, femoral bones)\] every 6 months for up to 18 months

New Skeletal-related events (SRE: pathologic fractures, need for bone radiation therapy or surgery) following 8 cycles (day 168) of therapy

New Skeletal-related Events (SRE: Pathologic Fractures, Need for Bone Radiation Therapy or Surgery) after 18 months post VD

Bone remodelling was studied by the measurement of the following serum indices on day 21 of cycle 4 (day 84) using an enzyme-linked immunosorbent assay (ELISA) bone formation marker \[bone-specific alkaline phosphatase (bALP)\].

Bone remodelling was studied by the measurement of the following serum indices on day 21 of cycle 4 (day 84) using an enzyme-linked immunosorbent assay (ELISA): bone formation marker \[bone-specific alkaline phosphatase (bALP) \].

University of Athens

Director of the clinic

For this study, Velcade will be administered at the standard dose of 1.3 mg/m2, iv, bolus, on days 1, 4, 8 and 11 of a 21-day cycle.

Dexamethasone will be administered at a dose of 12 mg/m2 p.o., on days 1-2, 4-5, 8-9 and 11-12 of the same cycle.

Zoledronic acid will be administered at a dose of 4 mg, iv (15-minute infusion), every 28 days for up to 8 cycles, and then every 28 days for the next 18 months

Bortezomib: 1.3 mg/m2, iv, bolus, on days 1, 4, 8 and 11 of a 21-day cycle for up to 8 chemotherapy cycles

Zoledronic Acid: 4 mg, iv, at a 15 min infusion, Day 1 of every cycle for up to 8 cycles, and then every 28 days for the next 18 months

Dexamethasone: 12 mg/m2 p.o. on days 1-2, 4-5, 8-9 and 11-12 of a 21-day cycle for up to 8 chemotherapy cycles

Bortezomib/Dexamethasone/Zoledronic Acid

Age, Categorical

Sex: Female, Male

Greece

Region of Enrollment

Lumbar spine (L1-L4)

Femoral neck (FN)

Bone Mineral Density of the lumbar spine (L1-L4, anteroposterior view) and femoral neck (FN) was measured by Dual Energy X-Absorptiometry scan (DEXA-scan) using a Hologic QDR-1000 scanner

Bone remodelling was studied by the measurement of the following serum bone metabolism parameters indices using an enzyme-linked immunosorbent assay (ELISA): i) bone resorption marker C-terminal cross-linking telopeptide of collagen type I (CTX) and ii) bone formation marker \[osteocalcin (OC)\].

Bone remodelling

Skeletal survey was measured using conventional radiography \[imaging of the whole skeleton (skull, cervical spine, thoracic spine, lumbar spine, pelvis, humeri, femoral bones)\].

Skeletal survey for osteolytic lesions/fractures

Bone pain was measured with the use of the Visual Analogue Scale. The visual analogue scale or visual analog scale (VAS) is a psychometric response scale which can be used in questionnaires. It is a measurement instrument for subjective characteristics or attitudes that cannot be directly measured.

The VAS for Bone Pain was constructed as follows:

None Mild Moderate Severe Worst possible 1,2 3,4 5,6 7,8 9,10 Lower values are considered to be of a better outcome, higher values are considered to be of a worst outcome.

Bone pain

Bone remodelling was studied by the measurement of the following serum bone metabolism parameters indices using an enzyme-linked immunosorbent assay (ELISA) bone formation marker \[bone-specific alkaline phosphatase (bALP)\].

Prof. M. A. Dimopoulos

Out of the 17 patients enrolled 12 patients completed the 8 VD cycles, 2 patients 6 VD cycles (due to peripheral neuropathy), 1 patient 5 VD cycles (and then progressed) and 2 patients died after receiving 1 and 2 VD cycles (respectively)

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Atrasentan and Zometa for Men With Prostate Cancer Metastatic to Bone	NCT00181558	Prostate Cancer Adenocarcinoma ...	Atrasentan Zoledronic Acid...	18 Years -	Massachusetts General Hospital
Effect of Combination of Bortezomib/Dexamethasone/Zoledronic Acid on Bone Disease in Patients With Multiple Myeloma Relapsed After 1-3 Prior Lines of Therapy	NCT00972959	Multiple Myelom...	Bortezomib Zoledronic Acid Dexamethasone	18 Years -	University of Athens
Effect of Combination of Bortezomib/Dexamethasone/Zoledronic Acid on Bone Disease in Patients With Multiple Myeloma Relapsed After 1-3 Prior Lines of Therapy	NCT00972959	Multiple Myelom...	Bortezomib Zoledronic Acid Dexamethasone	18 Years -	University of Athens

Spots Global Cancer Trial Database for zoledronic acid (zometa)