Zolendronate for the Prevention of Bone Loss in Men w/ Prostate CA on Long-Term Androgen Deprivation

• Sponsor: Northwestern University (Other)
• Overall Status: Terminated
• CT.gov ID: NCT00058188
• Collaborator: Novartis (Industry)
• Enrollment: 53
• Locations: 3
• Arms: 2
• Actual Duration (Months): 68.1
• Patients Per Site: 17.7
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

RATIONALE: Zoledronate may prevent bone loss associated with long term androgen deprivation therapy. It is not yet known whether zoledronate combined with calcium is more effective than calcium alone in preventing bone loss.

PURPOSE: Randomized phase III trial to compare the effectiveness of zoledronate combined with calcium with that of calcium alone in preventing bone loss in patients with stage III or stage IV prostate cancer who have received long-term androgen deprivation therapy.

Condition or Disease	Intervention/Treatment	Phase
Osteoporosis; Prostate Cancer	Dietary Supplement: cholecalciferol; Drug: calcium gluconate; Drug: zoledronic acid	Phase 3

Detailed Description

OBJECTIVES:

• Compare bone loss in patients receiving long-term androgen deprivation therapy for stage III or IV prostate cancer when treated with supportive care with vs without zoledronate.

• Compare the percentage change in lumbar spine and hip bone density in patients treated with these regimens.

• Compare markers of bone formation and resorption in patients treated with these regimens.

• Compare the incidence of skeletal events (pathologic and non-pathologic bone fractures, spinal cord compression, surgery to bone, and radiotherapy to bone) in patients treated with these regimens.

• Compare the incidence of new or progressive bone metastatic disease in patients treated with these regimens.

• Compare the survival rate of patients treated with these regimens.

OUTLINE: Patients are stratified according to race (black vs other). Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive zoledronate IV over 15 minutes on day 1 and oral calcium gluconate and oral cholecalciferol daily. Courses repeat every 3 months for 12 months in the absence of toxicity.

• Arm II: Patients receive oral calcium gluconate and oral cholecalciferol as in arm I.

Patients are followed every 3 months.

PROJECTED ACCRUAL: A total of 72 patients (36 per treatment arm) will be accrued for this study.

Study Design

• Study Type: Interventional
• Actual Enrollment: 53 participants
• Allocation: Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Supportive Care
• Official Title: A Phase III Randomized Study of Zolendronate Bisphosphonate Therapy for the Prevention of Bone Loss in Men With Prostate Cancer Receiving Long-Term Androgen Deprivation
• Actual Study Start Date: Mar 1, 2003
• Actual Primary Completion Date: Nov 1, 2008
• Actual Study Completion Date: Nov 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm I Patients receive zoledronate IV over 15 minutes on day 1 and oral calcium gluconate and oral cholecalciferol daily. Courses repeat every 3 months for 12 months in the absence of toxicity.	Dietary Supplement: cholecalciferol; Given orally; Drug: calcium gluconate; Given orally; Drug: zoledronic acid; Given IV
Active Comparator: Arm II Patients receive oral calcium gluconate and oral cholecalciferol as in arm I.	Dietary Supplement: cholecalciferol; Given orally; Drug: calcium gluconate; Given orally

Outcome Measures

Primary Outcome Measures

1. Bone Density Change as Measured by Dual-energy X-ray Absorptiometry From Baseline to 13 Months [Bone scan taken at baseline and month 13]

   To assess bone density change as measured by dual-energy x-ray absorptiometry

Secondary Outcome Measures

1. Percentage Change in Lumbar Spine and Hip Bone Density as Measured by Plain Film X-rays of Lumbar Spine and Pelvis From Baseline to 13 Months [Lumbar spine and hip bone density taken at baseline and month 13.]

   To assess the percentage change in lumbar spine and hip bone density as measured by plain film x-rays of lumbar spine and pelvis

2. Markers of Bone Formation and Resorption [Bone alkaline phosphatase taken at baseline, month 6 and month 13.]

   To assess markers of bone formation and resorption.

3. Incidence of Skeletal Events (Pathologic and Non-pathologic Bone Fractures, Spinal Cord Compression, Surgery to Bone, and Radiotherapy to Bone) [PSA taken at baseline, month 3, month 6, month 9, month 12 and month 13. CT scan of abdomen and pelvis taken at baseline and month 13. Serum testosterone, estradiol, parathyroid taken at baseline, month 6 and month 13.]

   To assess the incidence of skeletal events (pathologic and non-pathologic bone fractures, spinal cord compression, surgery to bone, and radiotherapy to bone)

4. Incidence of New or Progressive Bone Metastatic Disease [Serum osteocalcin and serum bone alkaline phosphatase taken at baseline, month 6 and month 13.]

   To assess the incidence of new or progressive bone metastatic disease

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

DISEASE CHARACTERISTICS:

• Histologically confirmed prostate cancer

• Stage III or IV disease

• Received at least 3 months of prior androgen deprivation therapy (no maximum amount/time) by either surgical or medical castration

• Medical castration may be by intermittent or continuous androgen suppression via single- or combined-drug androgen blockade

• Continued concurrent androgen deprivation therapy required throughout study participation

• No bone metastases by baseline bone scan

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• ECOG 0-2

Life expectancy

• At least 1 year

Hematopoietic

• Not specified

Hepatic

• Bilirubin less than 3 times upper limit of normal (ULN)

• AST and ALT less than 3 times ULN

• No chronic liver disease

Renal

• Creatinine no greater than 2.0 mg/dL

Other

• Fertile patients must use effective contraception

• No Paget's disease

• No Cushing's disease

• No hyperthyroidism

• No hyperprolactinemia

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Not specified

Chemotherapy

• Prior chemotherapy for prostate cancer allowed

Endocrine therapy

• See Disease Characteristics

• More than 12 months since prior suppressive doses of thyroxine or calcitonin

• More than 6 months since prior corticosteroids

• Concurrent corticosteroids allowed (after enrollment on study)

Radiotherapy

• Prior radiotherapy for prostate cancer allowed

Surgery

• See Disease Characteristics

Other

• More than 12 months since prior bisphosphonate therapy (oral or IV)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Northwestern University	Chicago	Illinois	United States	60611-3013
2	Veterans Affairs Medical Center - Lakeside Chicago	Chicago	Illinois	United States	60611
3	John H. Stroger Hospital of Cook County	Chicago	Illinois	United States	60612

Sponsors and Collaborators

• Northwestern University
• Novartis

Investigators

• Study Chair: Charles L. Bennett, MD, PhD, Robert H. Lurie Cancer Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Northwestern University
• ClinicalTrials.gov Identifier: NCT00058188
• Other Study ID Numbers: NU 02U1
• First Posted: Apr 9, 2003
• Last Update Posted: Dec 8, 2020
• Last Verified: Oct 1, 2020

• Keywords provided by Northwestern University: osteoporosis; stage III prostate cancer; stage IV prostate cancer
• Additional relevant MeSH terms: Prostatic Neoplasms; Osteoporosis; Cholecalciferol; Vitamin D; Zoledronic Acid; Calcium

Study Results

Participant Flow

Recruitment Details	PIs departure from the institution was sudden and due unforeseen serious circumstances. Due to this, no data was collected for this study nor can be reported on.

Arm/Group Title	Treatment With Zoledronate, Calcium and Cholecalciferol	Treatment With Calcium and Cholecalciferol
Arm/Group Description	Patients receive zoledronate IV over 15 minutes on day 1 and oral calcium gluconate and oral cholecalciferol daily. Courses repeat every 3 months for 12 months in the absence of toxicity. cholecalciferol: Given orally calcium gluconate: Given orally zoledronic acid: Given IV	Patients receive oral calcium gluconate and oral cholecalciferol as in arm I. cholecalciferol: Given orally calcium gluconate: Given orally
Period Title: Overall Study
STARTED	0	0
COMPLETED	0	0
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Treatment With Zoledronate, Calcium and Cholecalciferol	Treatment With Calcium and Cholecalciferol	Total
Arm/Group Description	Patients receive zoledronate IV over 15 minutes on day 1 and oral calcium gluconate and oral cholecalciferol daily. Courses repeat every 3 months for 12 months in the absence of toxicity. cholecalciferol: Given orally calcium gluconate: Given orally zoledronic acid: Given IV	Patients receive oral calcium gluconate and oral cholecalciferol as in arm I. cholecalciferol: Given orally calcium gluconate: Given orally	Total of all reporting groups
Overall Participants	0	0	0
Age () []
<=18 years
Between 18 and 65 years
>=65 years
Sex: Female, Male () []
Female
Male

Outcome Measures

1. Primary Outcome

Title	Bone Density Change as Measured by Dual-energy X-ray Absorptiometry From Baseline to 13 Months
Description	To assess bone density change as measured by dual-energy x-ray absorptiometry
Time Frame	Bone scan taken at baseline and month 13

Outcome Measure Data

Analysis Population Description

Due to the unique situation of the PI, no data was collected for this study nor can be reported on.

Arm/Group Title	Treatment With Zoledronate, Calcium and Cholecalciferol	Treatment With Calcium and Cholecalciferol
Arm/Group Description	Patients receive zoledronate IV over 15 minutes on day 1 and oral calcium gluconate and oral cholecalciferol daily. Courses repeat every 3 months for 12 months in the absence of toxicity. cholecalciferol: Given orally calcium gluconate: Given orally zoledronic acid: Given IV	Patients receive oral calcium gluconate and oral cholecalciferol as in arm I. cholecalciferol: Given orally calcium gluconate: Given orally
Measure Participants	0	0

2. Secondary Outcome

Title	Percentage Change in Lumbar Spine and Hip Bone Density as Measured by Plain Film X-rays of Lumbar Spine and Pelvis From Baseline to 13 Months
Description	To assess the percentage change in lumbar spine and hip bone density as measured by plain film x-rays of lumbar spine and pelvis
Time Frame	Lumbar spine and hip bone density taken at baseline and month 13.

Outcome Measure Data

Analysis Population Description

Due to the unique situation of the PI, no data was collected for this study nor can be reported on.

Arm/Group Title	Treatment With Zoledronate, Calcium and Cholecalciferol	Treatment With Calcium and Cholecalciferol
Arm/Group Description	Patients receive zoledronate IV over 15 minutes on day 1 and oral calcium gluconate and oral cholecalciferol daily. Courses repeat every 3 months for 12 months in the absence of toxicity. cholecalciferol: Given orally calcium gluconate: Given orally zoledronic acid: Given IV	Patients receive oral calcium gluconate and oral cholecalciferol as in arm I. cholecalciferol: Given orally calcium gluconate: Given orally
Measure Participants	0	0

3. Secondary Outcome

Title	Markers of Bone Formation and Resorption
Description	To assess markers of bone formation and resorption.
Time Frame	Bone alkaline phosphatase taken at baseline, month 6 and month 13.

Outcome Measure Data

Analysis Population Description

Due to the unique situation of the PI, no data was collected for this study nor can be reported on.

Arm/Group Title	Treatment With Zoledronate, Calcium and Cholecalciferol	Treatment With Calcium and Cholecalciferol
Arm/Group Description	Patients receive zoledronate IV over 15 minutes on day 1 and oral calcium gluconate and oral cholecalciferol daily. Courses repeat every 3 months for 12 months in the absence of toxicity. cholecalciferol: Given orally calcium gluconate: Given orally zoledronic acid: Given IV	Patients receive oral calcium gluconate and oral cholecalciferol as in arm I. cholecalciferol: Given orally calcium gluconate: Given orally
Measure Participants	0	0

4. Secondary Outcome

Title	Incidence of Skeletal Events (Pathologic and Non-pathologic Bone Fractures, Spinal Cord Compression, Surgery to Bone, and Radiotherapy to Bone)
Description	To assess the incidence of skeletal events (pathologic and non-pathologic bone fractures, spinal cord compression, surgery to bone, and radiotherapy to bone)
Time Frame	PSA taken at baseline, month 3, month 6, month 9, month 12 and month 13. CT scan of abdomen and pelvis taken at baseline and month 13. Serum testosterone, estradiol, parathyroid taken at baseline, month 6 and month 13.

Outcome Measure Data

Analysis Population Description

Due to the unique situation of the PI, no data was collected for this study nor can be reported on.

Arm/Group Title	Treatment With Zoledronate, Calcium and Cholecalciferol	Treatment With Calcium and Cholecalciferol
Arm/Group Description	Patients receive zoledronate IV over 15 minutes on day 1 and oral calcium gluconate and oral cholecalciferol daily. Courses repeat every 3 months for 12 months in the absence of toxicity. cholecalciferol: Given orally calcium gluconate: Given orally zoledronic acid: Given IV	Patients receive oral calcium gluconate and oral cholecalciferol as in arm I. cholecalciferol: Given orally calcium gluconate: Given orally
Measure Participants	0	0

5. Secondary Outcome

Title	Incidence of New or Progressive Bone Metastatic Disease
Description	To assess the incidence of new or progressive bone metastatic disease
Time Frame	Serum osteocalcin and serum bone alkaline phosphatase taken at baseline, month 6 and month 13.

Outcome Measure Data

Analysis Population Description

Due to the unique situation of the PI, no data was collected for this study nor can be reported on.

Arm/Group Title	Treatment With Zoledronate, Calcium and Cholecalciferol	Treatment With Calcium and Cholecalciferol
Arm/Group Description	Patients receive zoledronate IV over 15 minutes on day 1 and oral calcium gluconate and oral cholecalciferol daily. Courses repeat every 3 months for 12 months in the absence of toxicity. cholecalciferol: Given orally calcium gluconate: Given orally zoledronic acid: Given IV	Patients receive oral calcium gluconate and oral cholecalciferol as in arm I. cholecalciferol: Given orally calcium gluconate: Given orally
Measure Participants	0	0

Adverse Events

Time Frame	Adverse events timeframe is not known. There is no data for this study.
Adverse Event Reporting Description	Due to the unique situation of the PI, no data was collected for this study nor can be reported on.
Arm/Group Title	Treatment With Zoledronate, Calcium and Cholecalciferol		Treatment With Calcium and Cholecalciferol
Arm/Group Description	Patients receive zoledronate IV over 15 minutes on day 1 and oral calcium gluconate and oral cholecalciferol daily. Courses repeat every 3 months for 12 months in the absence of toxicity. cholecalciferol: Given orally calcium gluconate: Given orally zoledronic acid: Given IV		Patients receive oral calcium gluconate and oral cholecalciferol as in arm I. cholecalciferol: Given orally calcium gluconate: Given orally
All Cause Mortality
	Treatment With Zoledronate, Calcium and Cholecalciferol		Treatment With Calcium and Cholecalciferol
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/0 (NaN)		0/0 (NaN)
Serious Adverse Events
	Treatment With Zoledronate, Calcium and Cholecalciferol		Treatment With Calcium and Cholecalciferol
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/0 (NaN)		0/0 (NaN)
Other (Not Including Serious) Adverse Events
	Treatment With Zoledronate, Calcium and Cholecalciferol		Treatment With Calcium and Cholecalciferol
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/0 (NaN)		0/0 (NaN)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.