Effect of Zoledronic Acid on Chemotherapy Induced Bone Loss

• Sponsor: M.D. Anderson Cancer Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT00352846
• Collaborator: Novartis (Industry)
• Enrollment: 135
• Location: 1
• Arms: 2
• Duration (Months): 68
• Patients Per Site Per Month: 2

Study Details

Study Description

Brief Summary

Primary Objective:

• Evaluate the effect of zoledronate on change in bone mineral density (BMD) at the total lumbar spine and femoral neck.

Secondary Objectives:

• Evaluate the effect of zoledronate on change in BMD at the total hip

• Evaluate risk factors for developing osteoporosis on chemotherapy

• Determine correlative markers for response to zoledronate 4. Evaluate zoledronate effect on new bone fractures 5. Evaluate the cost-effectiveness of zoledronic acid (with calcium and vitamin D) versus standard treatment (calcium and vitamin D alone).

Condition or Disease	Intervention/Treatment	Phase
Non-Hodgkin's Lymphoma; Lymphoma	Drug: Zoledronic Acid; Drug: Vitamin D; Drug: Calcium Carbonate	Phase 3

Detailed Description

Medicines called "bisphosphonates" have been shown to help people with cancer that has spread to their bones. Zoledronic acid is a "bisphosphonate". Some bisphosphonates are pills that can be swallowed. Other bisphosphonates such as zoledronic acid need to be given by vein (or intravenously). Some studies have shown that people with multiple myeloma, breast cancer, and prostate cancer that had spread to the bone had less side effects from their bone disease when they were treated with bisphosphonates by vein.

If you are found to be eligible to take part in this study, you will be randomly assigned (as in the toss of a coin) to one of two treatment groups. Participants in one group will receive standard care with calcium and Vitamin D alone. Participants in the other group will receive standard care with calcium and Vitamin D plus zoledronic acid. There is an equal chance of being assigned to either group. Both you and your study doctor will know if you are being treated with zoledronic acid.

You will be asked to come to the doctor's clinic 5 times over about 12 months (at the start of the study [baseline] and then every 3 months). Each visit should take about 1 hour. Participants in the zoledronic acid group will receive an infusion of zoledronic acid by vein at baseline and at 6 months into the study. The infusion will last about 30 minutes. This infusion procedure may or may not be done at the same time as your already scheduled chemotherapy treatment.

You will take calcium and Vitamin D pills while on study at amounts recommended for prevention of osteoporosis.

You will have a physical exam done at every visit. Various x-rays and/or bone density scans will be repeated after 12 months. Your doctor may also want to do additional bone density or x-ray scans if you have new symptoms or your symptoms get worse.

Before each treatment, you will have a blood test (about 1-2 teaspoons of blood) to make sure your kidneys are okay before each treatment with zoledronic acid. At each visit. your doctor or nurse will ask you how you are feeling and will ask about any medications you are taking or any medical problems you have had since your last visit. You will be asked to complete questionnaires about how you are feeling at certain visits. These questionnaires are 1 page long and should only take a few minutes to complete.

It is anticipated that your participation in this study will be 12 months. If your cancer gets worse, or if your doctor feels that you should be treated with a different medicine, you will be taken off of this study and your doctor will talk to you about other medicines that may be better for you.

Participants who received Zoledronic Acid will be contacted regularly to ask about any experience of osteonecrosis (bone death), for 10 years from the time they enroll on study. They will be interviewed by telephone call every 6 months.

This is an investigational study. Zoledronic acid is approved by the FDA for the treatment of high calcium levels in the blood. Zoledronic acid has not been approved by the FDA for what it is being used for in this study. After the treatment ends, you may continue to receive zoledronic acid or a similar drug, if your cancer doctor feels that it would help you. About 72 patients will take part in this study. All will be enrolled at M. D. Anderson.

Study Design

• Study Type: Interventional
• Actual Enrollment: 135 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Effect of Zoledronic Acid on Chemotherapy Induced Bone Loss in Non-Hodgkin's Lymphoma Patients Receiving Chemotherapy
• Study Start Date: Jan 1, 2006
• Actual Primary Completion Date: Sep 1, 2011
• Actual Study Completion Date: Sep 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Vitamin D + Calcium Carbonate Oral Vitamin D 400 mg daily + Calcium 1200 mg daily	Drug: Vitamin D; 400 mg by mouth daily; Drug: Calcium Carbonate; 1200 mg by mouth daily
Experimental: Vitamin D + Calcium Carbonate + Zoledronic Acid Oral Vitamin D 400 mg daily and Calcium 1200 mg daily; Zoledronic Acid 4 mg/m^2 intravenous at baseline and 6 months.	Drug: Zoledronic Acid; 4 mg/m^2 by vein over 30 Minutes at baseline and 6 months.; Other Names: Zometa Zoledronate ; Drug: Vitamin D; 400 mg by mouth daily; Drug: Calcium Carbonate; 1200 mg by mouth daily

Outcome Measures

Primary Outcome Measures

1. Percentage Change in Bone Mineral Density (BMD) T-Score From Baseline to 12 Months [From baseline to 12 Months]

   The 12-month change from baseline in BMD at the total lumbar spine. BMD evaluation was performed at baseline and at 12 months after initiation of therapy at the lumbar spine. BMD was measured by dual-energy, x-ray absorptiometry scanners. T-Score is the number of standard deviations above or below the mean. A T-score >= -1 indicates a normal BMD, while T-scores between -1 and -2.5 indicate osteopenia and T-scores <= -2.5 indicate osteoporosis.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

1. Diagnosis of Non-Hodgkin's Lymphoma (B- or T-cell) or Hodgkin's lymphoma.

2. Prior Chemotherapy</= 4 weeks of treatment.

3. Age >/= 18 years old.

4. Eastern Cooperative Oncology Group (ECOG) Performance Status 0-3.

5. Estimated creatinine clearance >/= 60 ml/min.

6. Must sign an informed consent form.

Exclusion Criteria:

1. Radiologic evidence of vertebral or hip fracture.

2. BMD T-score less than (i.e., worse than or more negative than) -2.0 at any of the following sites: lumbar spine, femoral neck, or total hip.

3. Patients with secondary non-lymphomatous cancers metastatic to bone. However, other secondary cancers are allowed.

4. Spinal cord compression due to vertebral collapse.

5. Bisphosphonate treatment in the prior 6 months or steroid use (greater than 35 mg of prednisone equivalent steroids) in the prior 3 months. The use of topical, inhaled, or nasal steroids is allowed.

6. Primary hyperparathyroidism.

7. Active osteomalacia.

8. Untreated hypocalcemia (ionized, iCa), Ionized Ca level must be within normal limits prior to enrollment.

9. Untreated secondary hyperparathyroidism, Patients with abnormal parathyroid hormone (PTH) levels may be enrolled as long as they are being treated.

10. Untreated vitamin D deficiency, Vitamin D level may be abnormal and patient may be enrolled as long as they are being treated.

11. Untreated low testosterone (test in men only), testosterone level may be abnormal and patient may be enrolled as long as they are being treated.

12. Paget's disease.

13. Pregnant or breast-feeding.

14. Radiotherapy involving the mandible.

15. Current active dental problems including infection of the teeth or jawbone (maxilla or mandibular); dental or fixture trauma, or a current or prior diagnosis of osteonecrosis of the jaw (ONJ), or of exposed bone in the mouth, or of slow healing after dental procedures.

16. Recent (within 3 weeks) or planned dental or jaw surgery (e.g.. extraction, implants).

17. Patients with abnormal renal function as evidenced by either a serum creatinine greater than 3 mg/dL or by a calculated creatinine clearance of < 60 mL/minute.

18. Known hypersensitivity to zoledronic acid or other bisphosphonates.

19. Hypercalcemia: corrected Ca > 10.2 mg/dL or ionized Ca > 1.32 mmol/L

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	UT MD Anderson Cancer Center	Houston	Texas	United States	77030

Sponsors and Collaborators

• M.D. Anderson Cancer Center
• Novartis

Investigators

• Principal Investigator: Fredrick Hagemeister, MD, M.D. Anderson Cancer Center

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• MD Anderson Cancer Center

Publications

None provided.

• Responsible Party: M.D. Anderson Cancer Center
• ClinicalTrials.gov Identifier: NCT00352846
• Other Study ID Numbers: 2005-0698
• First Posted: Jul 17, 2006
• Last Update Posted: Jul 2, 2013
• Last Verified: Jun 1, 2013

• Keywords provided by M.D. Anderson Cancer Center: Non-Hodgkin's Lymphoma; Lymphoma; Zoledronic Acid; Zoledronate; Zometa; Vitamin D; Calcium Carbonate; Bone Loss
• Additional relevant MeSH terms: Lymphoma; Lymphoma, Non-Hodgkin; Vitamin D; Zoledronic Acid; Calcium Carbonate; Calcium

Study Results

Participant Flow

Recruitment Details	Recruitment Period: 01/27/2006 to 08/13/2009. All recruitments done at UT MD Anderson Cancer Center.
Pre-assignment Detail	Of 135 enrolled participants, 61 were excluded from the trial before assignment to groups due to screen failures.

Arm/Group Title	Vitamin D + Calcium Carbonate	Vitamin D + Calcium Carbonate + Zoledronic Acid
Arm/Group Description	Oral Vitamin D 400 mg daily + Calcium 1200 mg daily	Oral Vitamin D 400 mg daily and Calcium 1200 mg daily; Zoledronic Acid 4 mg/m^2 intravenous at baseline and 6 months.
Period Title: Overall Study
STARTED	37	37
COMPLETED	29	24
NOT COMPLETED	8	13

Baseline Characteristics

Arm/Group Title	Vitamin D + Calcium Carbonate	Vitamin D + Calcium Carbonate + Zoledronic Acid	Total
Arm/Group Description	Oral Vitamin D 400 mg daily + Calcium 1200 mg daily	Oral Vitamin D 400 mg daily and Calcium 1200 mg daily; Zoledronic Acid 4 mg/m^2 intravenous at baseline and 6 months.	Total of all reporting groups
Overall Participants	37	37	74
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	57	61	57
Sex: Female, Male (Count of Participants)
Female	13 35.1%	14 37.8%	27 36.5%
Male	24 64.9%	23 62.2%	47 63.5%
Region of Enrollment (participants) [Number]
United States	37 100%	37 100%	74 100%

Outcome Measures

1. Primary Outcome

Title	Percentage Change in Bone Mineral Density (BMD) T-Score From Baseline to 12 Months
Description	The 12-month change from baseline in BMD at the total lumbar spine. BMD evaluation was performed at baseline and at 12 months after initiation of therapy at the lumbar spine. BMD was measured by dual-energy, x-ray absorptiometry scanners. T-Score is the number of standard deviations above or below the mean. A T-score >= -1 indicates a normal BMD, while T-scores between -1 and -2.5 indicate osteopenia and T-scores <= -2.5 indicate osteoporosis.
Time Frame	From baseline to 12 Months

Outcome Measure Data

Analysis Population Description

BMD data available on 53 evaluable participants upon treatment completion.

Arm/Group Title	Vitamin D + Calcium Carbonate	Vitamin D + Calcium Carbonate + Zoledronic Acid
Arm/Group Description	Oral Vitamin D 400 mg daily + Calcium 1200 mg daily	Oral Vitamin D 400 mg daily and Calcium 1200 mg daily; Zoledronic Acid 4 mg/m^2 intravenous at baseline and 6 months.
Measure Participants	29	24
Mean (Standard Deviation) [Percentage Change of BMD]	0.08 (0.34)	-0.09 (1.23)

Adverse Events

Time Frame	4 years, 3 months
Arm/Group Title	Vitamin D + Calcium Carbonate		Vitamin D + Calcium Carbonate + Zoledronic Acid
Arm/Group Description	Oral Vitamin D 400 mg daily + Calcium 1200 mg daily		Oral Vitamin D 400 mg daily and Calcium 1200 mg daily; Zoledronic Acid 4 mg/m^2 intravenous at baseline and 6 months.
All Cause Mortality
	Vitamin D + Calcium Carbonate		Vitamin D + Calcium Carbonate + Zoledronic Acid
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Vitamin D + Calcium Carbonate		Vitamin D + Calcium Carbonate + Zoledronic Acid
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/37 (0%)		0/37 (0%)
Other (Not Including Serious) Adverse Events
	Vitamin D + Calcium Carbonate		Vitamin D + Calcium Carbonate + Zoledronic Acid
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/37 (0%)		0/37 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE 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.