Effect of Zoledronic Acid on Chemotherapy Induced Bone Loss

This study has been completed.
Sponsor:
Collaborator:
Novartis
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:
NCT00352846
First received: July 13, 2006
Last updated: June 20, 2013
Last verified: June 2013
  Purpose

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 Intervention Phase
Non-Hodgkin's Lymphoma
Lymphoma
Drug: Zoledronic Acid
Drug: Vitamin D
Drug: Calcium Carbonate
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Effect of Zoledronic Acid on Chemotherapy Induced Bone Loss in Non-Hodgkin's Lymphoma Patients Receiving Chemotherapy

Resource links provided by NLM:


Further study details as provided by M.D. Anderson Cancer Center:

Primary Outcome Measures:
  • Percentage Change in Bone Mineral Density (BMD) T-Score From Baseline to 12 Months [ Time Frame: From baseline to 12 Months ] [ Designated as safety issue: No ]
    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.


Enrollment: 135
Study Start Date: January 2006
Study Completion Date: September 2011
Primary Completion Date: September 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00352846

Locations
United States, Texas
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
  More Information

Additional Information:
No publications provided by M.D. Anderson Cancer Center

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT00352846     History of Changes
Other Study ID Numbers: 2005-0698
Study First Received: July 13, 2006
Results First Received: April 30, 2013
Last Updated: June 20, 2013
Health Authority: United States: Institutional Review Board

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, Non-Hodgkin
Lymphoma
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Vitamin D
Ergocalciferols
Vitamins
Zoledronic acid
Calcium, Dietary
Diphosphonates
Calcium Carbonate
Micronutrients
Growth Substances
Physiological Effects of Drugs
Pharmacologic Actions
Bone Density Conservation Agents
Antacids
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 18, 2014