A Study of Zoledronic Acid in the Prevention of Cancer Therapy-induced Bone Loss

• Sponsor: Novartis Pharmaceuticals (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT00333229
• Collaborator: (none)
• Enrollment: 11
• Location: 1
• Arms: 2
• Duration (Months): 93
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

Breast cancer and osteoporosis are two of the most frequent diseases in women. Estrogen may be associated with bone loss and the risk of breast cancer because of its potent effects on the mitotic activity of breast epithelium and on bone turnover.

This study is will assess the safety and efficacy of Zoledronic acid 4 mg, given every 3 months over 24 months, in improving bone mineral density in premenopausal women with hormone receptor negative breast cancer and adjuvant chemotherapeutic treatment compared to placebo.

This study is not recruiting patients in the United States.

Condition or Disease	Intervention/Treatment	Phase
Primary Hormone Receptor Negative Breast Cancer in Premenopausal Women	Drug: Zoledronic Acid; Drug: Placebo	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 11 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Influence of Zoledronic Acid on Bone Mineral Density and Bone Ultrasonometry in Premenopausal Women With Hormone Receptor Negative Breast Cancer and Adjuvant Chemotherapeutic Treatment
• Study Start Date: Mar 1, 2006
• Actual Primary Completion Date: Dec 1, 2013
• Actual Study Completion Date: Dec 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Zoledronic Acid Patients randomized into the Zometa arm received a total of 8 study drug infusions which were applied every 3 months. Patients received treatment for 24 months every 3 months.	Drug: Zoledronic Acid; 4 mg zoledronic acid in 5 mL concentrate solution. Plastic vials.
Placebo Comparator: Placebo Patients randomized into the Placebo Arm received a total of 8 placebo infusions which were applied every 3 months. Patients received treatment for 24 months every 3 months.	Drug: Placebo; Matching Placebo

Outcome Measures

Primary Outcome Measures

1. Change in Bone Mineral Density (BMD) Measured by DXA at Lumbar Spine (L2-L4) Between Baseline and 24 Months. [24 months]

Secondary Outcome Measures

1. Bone Mineral Density (BMD) Measured by QUS at os Calcis and Phalanges After 24 Months [2 years]

2. Course of Biochemical Markers of Bone Turn Over (FSH, Estradiol (E2), Osteocalcin, PINP, Procollagene-I-peptid, Deoxypyridinoline in Serum) [2 years]

3. Pathologic Fractures During 24 Month [2 years]

4. Development of Metastases as Assessed by X-ray, CT, or MRI During 24 Months and During 60 Months [2 years]

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Female patients with histologically confirmed incident invasive breast cancer (T1-4) with no evidence of regional lymph node metastasis (N0) or distant metastasis (M0) and after complete primary tumor resection and axillary lymph node dissection less than 90 days before start of study drug treatment.

• Hormone receptor status is negative

• Patient is premenopausal (spontaneous and regular menses with premenopausal estradiol levels (>10ng/dL)

• Patient receives adjuvant standard chemotherapy with approved cytotoxic chemotherapeutic drugs (e.g. AC 4-6 cycles) (prior neoadjuvant CT is allowed)

• Bone density at study entry > -2.5 T-Score

Exclusion Criteria:

• Prior treatment with bisphosphonates and estrogens or treatments for osteoporosis in addition to calcium and vitamin D

• Severe physical or psychological concomitant diseases and other known concurrent, severe medical disorder jeopardizing the life of the patient in the immediate future (e.g., myocardial infarction in previous six months, angina pectoris despite treatment, uncontrolled severe arterial hypertension, progressive cardiac or respiratory failure)

• Known hypersensitivity to bisphosphonates

• Abnormal renal function

• 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), of exposed bone in the mouth, or of slow healing after dental procedures and recent (within 6 weeks) or planned dental or jaw surgery (e.g. extraction, implants)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novartis Investigative Site	Marburg		Germany	35043

Sponsors and Collaborators

• Novartis Pharmaceuticals

Investigators

• Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals
• Study Director: Novartis Pharmaceuticals, Novartis Pharmeceuticals

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Visit NovartisClinicalTrials.com: Pre-qualify for a trial, and view a list of trials and participating study centers.

Publications

None provided.

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT00333229
• Other Study ID Numbers: CZOL446GDE13; 2004-002831-14
• First Posted: Jun 2, 2006
• Last Update Posted: Nov 25, 2014
• Last Verified: Nov 1, 2014

• Keywords provided by Novartis Pharmaceuticals: Breast Cancer; premenopausal; Bone Mineral density; Cancer therapy induced bone loss; zoledronic acid
• Additional relevant MeSH terms: Breast Neoplasms; Zoledronic Acid

Study Results

Participant Flow

Arm/Group Title	Zoledronic Acid	Placebo
Arm/Group Description	Patients randomized into the Zometa arm received a total of 8 study drug infusions which were applied every 3 months. Patients received treatment for 24 months every 3 months.	Patients randomized into the Placebo Arm received a total of 8 placebo infusions which were applied every 3 months. Patients received treatment for 24 months every 3 months.
Period Title: Overall Study
STARTED	6	5
COMPLETED	6	4
NOT COMPLETED	0	1

Baseline Characteristics

Arm/Group Title	Zoledronic Acid	Placebo	Total
Arm/Group Description	Patients randomized into the Zometa arm received a total of 8 study drug infusions which were applied every 3 months. Patients received treatment for 24 months every 3 months.	Patients randomized into the Placebo Arm received a total of 8 placebo infusions which were applied every 3 months. Patients received treatment for 24 months every 3 months.	Total of all reporting groups
Overall Participants	6	5	11
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	41.2 (6.2)	43.2 (2.6)	42.1 (4.8)
Sex: Female, Male (Count of Participants)
Female	6 100%	5 100%	11 100%
Male	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

Title	Change in Bone Mineral Density (BMD) Measured by DXA at Lumbar Spine (L2-L4) Between Baseline and 24 Months.
Time Frame	24 months

Outcome Measure Data

Analysis Population Description

Analysis was not completed as study was not adequately powered due to premature study termination.

Arm/Group Title	Zoledronic Acid	Placebo
Arm/Group Description	Patients randomized into the Zometa arm received a total of 8 study drug infusions which were applied every 3 months. Patients received treatment for 24 months every 3 months.	Patients randomized into the Placebo Arm received a total of 8 placebo infusions which were applied every 3 months. Patients received treatment for 24 months every 3 months.
Measure Participants	0	0

2. Secondary Outcome

Title	Bone Mineral Density (BMD) Measured by QUS at os Calcis and Phalanges After 24 Months
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Zoledronic Acid	Placebo
Arm/Group Description	Patients randomized into the Zometa arm received a total of 8 study drug infusions which were applied every 3 months. Patients received treatment for 24 months every 3 months.	Patients randomized into the Placebo Arm received a total of 8 placebo infusions which were applied every 3 months. Patients received treatment for 24 months every 3 months.
Measure Participants	0	0

3. Secondary Outcome

Title	Course of Biochemical Markers of Bone Turn Over (FSH, Estradiol (E2), Osteocalcin, PINP, Procollagene-I-peptid, Deoxypyridinoline in Serum)
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Zoledronic Acid	Placebo
Arm/Group Description	Patients randomized into the Zometa arm received a total of 8 study drug infusions which were applied every 3 months. Patients received treatment for 24 months every 3 months.	Patients randomized into the Placebo Arm received a total of 8 placebo infusions which were applied every 3 months. Patients received treatment for 24 months every 3 months.
Measure Participants	0	0

4. Secondary Outcome

Title	Pathologic Fractures During 24 Month
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Zoledronic Acid	Placebo
Arm/Group Description	Patients randomized into the Zometa arm received a total of 8 study drug infusions which were applied every 3 months. Patients received treatment for 24 months every 3 months.	Patients randomized into the Placebo Arm received a total of 8 placebo infusions which were applied every 3 months. Patients received treatment for 24 months every 3 months.
Measure Participants	0	0

5. Secondary Outcome

Title	Development of Metastases as Assessed by X-ray, CT, or MRI During 24 Months and During 60 Months
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Zoledronic Acid	Placebo
Arm/Group Description	Patients randomized into the Zometa arm received a total of 8 study drug infusions which were applied every 3 months. Patients received treatment for 24 months every 3 months.	Patients randomized into the Placebo Arm received a total of 8 placebo infusions which were applied every 3 months. Patients received treatment for 24 months every 3 months.
Measure Participants	0	0

Adverse Events

Arm/Group Title	Placebo		Zoledronic Acid
Arm/Group Description	Patients randomized into the Placebo Arm received a total of 8 placebo infusions which were applied every 3 months. Patients received treatment for 24 months every 3 months.		Patients randomized into the Zometa arm received a total of 8 study drug infusions which were applied every 3 months. Patients received treatment for 24 months every 3 months.
All Cause Mortality
	Placebo		Zoledronic Acid
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Placebo		Zoledronic Acid
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/5 (20%)		1/6 (16.7%)
Eye disorders
VISUAL IMPAIRMENT	1/5 (20%)		0/6 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
BENIGN BREAST NEOPLASM	0/5 (0%)		1/6 (16.7%)
Nervous system disorders
HEADACHE	1/5 (20%)		0/6 (0%)
Other (Not Including Serious) Adverse Events
	Placebo		Zoledronic Acid
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/5 (100%)		6/6 (100%)
Ear and labyrinth disorders
TINNITUS	1/5 (20%)		0/6 (0%)
VERTIGO	0/5 (0%)		1/6 (16.7%)
Endocrine disorders
AUTOIMMUNE THYROIDITIS	1/5 (20%)		0/6 (0%)
Eye disorders
DRY EYE	1/5 (20%)		0/6 (0%)
Gastrointestinal disorders
ABDOMINAL PAIN UPPER	1/5 (20%)		0/6 (0%)
DYSPEPSIA	0/5 (0%)		1/6 (16.7%)
GASTRITIS	0/5 (0%)		1/6 (16.7%)
HAEMORRHOIDS	1/5 (20%)		0/6 (0%)
NAUSEA	2/5 (40%)		2/6 (33.3%)
General disorders
ASTHENIA	1/5 (20%)		0/6 (0%)
CHEST PAIN	0/5 (0%)		1/6 (16.7%)
INFLUENZA LIKE ILLNESS	0/5 (0%)		1/6 (16.7%)
MUCOSAL DRYNESS	1/5 (20%)		0/6 (0%)
PAIN	1/5 (20%)		1/6 (16.7%)
Hepatobiliary disorders
HEPATIC STEATOSIS	1/5 (20%)		0/6 (0%)
Infections and infestations
FOLLICULITIS	1/5 (20%)		0/6 (0%)
FURUNCLE	0/5 (0%)		1/6 (16.7%)
INFLUENZA	0/5 (0%)		2/6 (33.3%)
NASOPHARYNGITIS	0/5 (0%)		1/6 (16.7%)
ORAL HERPES	0/5 (0%)		1/6 (16.7%)
Investigations
HEPATIC ENZYME INCREASED	2/5 (40%)		1/6 (16.7%)
Metabolism and nutrition disorders
HYPERCHOLESTEROLAEMIA	1/5 (20%)		0/6 (0%)
HYPOKALAEMIA	0/5 (0%)		1/6 (16.7%)
TYPE 2 DIABETES MELLITUS	1/5 (20%)		0/6 (0%)
Musculoskeletal and connective tissue disorders
ARTHRALGIA	3/5 (60%)		3/6 (50%)
BACK PAIN	1/5 (20%)		1/6 (16.7%)
BONE PAIN	2/5 (40%)		3/6 (50%)
MYALGIA	1/5 (20%)		0/6 (0%)
MYOSCLEROSIS	0/5 (0%)		1/6 (16.7%)
OSTEOCHONDROSIS	1/5 (20%)		0/6 (0%)
PAIN IN EXTREMITY	0/5 (0%)		1/6 (16.7%)
RHEUMATIC FEVER	1/5 (20%)		0/6 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MELANOCYTIC NAEVUS	0/5 (0%)		1/6 (16.7%)
THYROID NEOPLASM	0/5 (0%)		1/6 (16.7%)
Nervous system disorders
AMNESIA	1/5 (20%)		0/6 (0%)
HEADACHE	0/5 (0%)		1/6 (16.7%)
LOSS OF CONSCIOUSNESS	0/5 (0%)		1/6 (16.7%)
PARAESTHESIA	3/5 (60%)		2/6 (33.3%)
SYNCOPE	0/5 (0%)		1/6 (16.7%)
Psychiatric disorders
CONVERSION DISORDER	1/5 (20%)		0/6 (0%)
DEPRESSION	0/5 (0%)		1/6 (16.7%)
SLEEP DISORDER	2/5 (40%)		0/6 (0%)
Reproductive system and breast disorders
MENOPAUSAL SYMPTOMS	1/5 (20%)		1/6 (16.7%)
POSTMENOPAUSAL HAEMORRHAGE	0/5 (0%)		1/6 (16.7%)
UTERINE POLYP	0/5 (0%)		1/6 (16.7%)
Respiratory, thoracic and mediastinal disorders
COUGH	0/5 (0%)		1/6 (16.7%)
DYSPHONIA	1/5 (20%)		0/6 (0%)
OROPHARYNGEAL PAIN	0/5 (0%)		1/6 (16.7%)
Skin and subcutaneous tissue disorders
DRUG REACTION WITH EOSINOPHILIA AND SYSTEMIC SYMPTOMS	0/5 (0%)		1/6 (16.7%)
Vascular disorders
HOT FLUSH	2/5 (40%)		2/6 (33.3%)
LYMPHOEDEMA	3/5 (60%)		5/6 (83.3%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of pooled data (i.e.,data from all sites) in clinical trial or disclosure of trial results in their entirety.