Effect of Zoledronic Acid as Anti-Cancer Treatment in Metastatic Breast Cancer Patients (MACS1295)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01129336
Recruitment Status : Completed
First Posted : May 24, 2010
Results First Posted : February 12, 2014
Last Update Posted : May 20, 2014
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Brief Summary:
This study will evaluate zoledronic acid's anti-cancer effects and Circulating Tumor Cell (CTCs) measurements in patients with HER2-negative metastatic breast cancer without bone metastasis.

Condition or disease Intervention/treatment Phase
First or Second Line HER2-negative Breast Cancer Metastatic Disease Without Bone Metastasis Drug: Zoledronic acid Drug: Standard Therapy Phase 4

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 44 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Multicenter, Open-label, Randomized Trial to Evaluate the Anti-cancer Effects of Zoledronic Acid and Circulating Tumor Cell Measurements in Patients With HER2-negative Metastatic Breast Cancer Without Bone Metastasis
Study Start Date : June 2010
Primary Completion Date : August 2012
Study Completion Date : August 2012

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer
U.S. FDA Resources

Arm Intervention/treatment
Experimental: Patients without bone metastases
Patients with no bone metastasis were randomized into a 1:1 ratio to standard therapy plus zoledronic acid 4mg IV Zoledronic acid administration monthly during Months 1-18.
Drug: Zoledronic acid
Patients with no bone metastasis (n=150) will receive Standard therapy plus Zoledronic acid administration 4 mg IV monthly during Months 1-18.
Other Names:
  • Zometa
  • bisphosphonates
  • CZOL446E
Experimental: Patients with bone metastases
Patients with bone metastasis received standard therapy + zoledronic acid for 18 months (discontinued upon disease progression/secondary malignancy)
Drug: Standard Therapy
Standard Therapy, including chemotherapy and hormonal therapy, was determined at the discretion of the investigator.

Primary Outcome Measures :
  1. Number of Participants With Progression Free Survival (PFS) [ Time Frame: up to 18 months ]
    Complete Response (CR): disappearance of all target lesions. Any pathological lymph nodes (target or non-target) must have exhibited a reduction in short axis to < 10 mm. Partial Response (PR): at least a 30% decrease in sum of diameters of target lesions, taking as reference the baseline sum of diameters. Progressive Disease (PD): at least 20% increase in sum of diameters of target lesions taking as reference the smallest sum on study accompanied by an absolute increase of at least 5 mm or appearance of one or more new lesions. Stable Disease (SD): neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference smallest sum diameters. PFS is time from enrollment to date of first documented disease progression or death due to any cause. A participant is considered to be censored when data on time to event is missing due to a subject being lost to follow-up or non-occurrence of the outcome event before the completion of the trial.

Secondary Outcome Measures :
  1. Percentage of Patients With Circulating Tumor Cell Levels of at Least 5 Per 7.5 mL of Peripheral Blood by Month [ Time Frame: Baseline, Month 1, 2, 4, 6, 9 and 18 ]
    Circulating tumor cells (CTCs) have been associated with poor patient prognosis and outcomes in patients receiving treatment for MBC. CTCs have been evaluated as a potential biomarker for predicting treatment effects and overall survival. Baseline was defined as the last predose measurement for patients who received any study drug and as the later of the screening visit or Visit 2 value for patients who did not receive the study drug. Percentage was calculated as the number of patients with CTC ≥5/7.5 mL against the number of patients with nonmissing CTC values (represented as 'n' in the categories).

  2. Time to Progression (TTP) [ Time Frame: up to 18 months ]
    Time to progression is defined as the time from the date of enrollment to the date of first documented disease progression or death due to metastatic breast cancer.

  3. Change From Baseline in Urine NTX by Month [ Time Frame: Baseline, Month 2, Month 4 ]
    NTX= N-telopeptide of type 1 collagen (nmol bce/mmol [nanomoles of bone collagen equivalents per millimole of creatinine]). Baseline was defined as the last predose measurement for patients who received any study drug and as the later of the screening visit or visit 2 value for patients who did not receive study drug.

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Written informed consent
  • Female patients (age ≥18 years)
  • HER2-negative metastatic breast cancer (stage IV)
  • Patients will be receiving chemotherapy or hormonal therapy
  • Patients with no bone metastasis and ≤1 prior treatments for metastatic breast cancer. Patients with newly diagnosed metastatic breast cancer may have received adjuvant or neoadjuvant chemotherapy as long as treatment was completed ≥12 months prior to relapse.
  • Asymptomatic brain metastasis is permitted if all of the following criteria are met:

    1. no sign of clinical progression or known progression of brain metastasis
    2. off steroids for at least 2 weeks prior to study enrollment
  • Stable renal function: two serum creatinine determinations of <3 mg/dL, obtained no less than 7 days apart (one value may be obtained within 6 weeks prior to Screening; the second must be obtained during Screening)
  • ECOG performance status of 0 or 1
  • Life expectancy of ≥ 6 months
  • Negative serum pregnancy test
  • Ability and willingness to comply with all study requirements

Exclusion Criteria:

  • Known hypersensitivity to zoledronic acid or other bisphosphonates
  • Patients with history of another malignancy within the last two years prior to study enrollment, except cured basal cell carcinoma of the skin or excised carcinoma in site of the cervix
  • Use of concurrent investigational agents is prohibited. Prior use of investigational agents is permitted if discontinued ≥30 days prior to Screening.
  • No prior therapy with an antiresorptive agent
  • Patients with active brain metastases or meningeal metastases
  • Current or recent (in the six months prior to initial study drug treatment) severe cardiovascular disease (defined as uncontrolled congestive heart failure), hypertension refractory to treatment, or poorly controlled Type I/II diabetes mellitus
  • Current active dental problems including dental abscess or infection of the jawbone (maxilla or mandible) or a current or prior diagnosis of osteonecrosis of the jaw
  • Patients who have received radiotherapy ≤ 4 weeks prior to study enrollment or who have not recovered from radiotherapy-related toxicities. Palliative radiotherapy for bone lesions ≤ 2 weeks prior to study enrollment is allowed
  • Patients who have undergone major surgery (e.g., intra-thoracic, intra-abdominal or intra-pelvic) ≤ 4 weeks prior to study enrollment or who have not recovered from side effects of such therapy
  • Diminished renal capacity: calculated creatinine clearance (CrCl) <30 mL/min (based on Cockcroft-Gault formula)
  • Corrected (i.e., adjusted for serum albumin) serum calcium of <8.0 mg/dL (2.00 mmol/L) or ≥ 12 mg/dL (3.00 mmol/L)
  • Pregnant or breast-feeding females
  • Women of child-bearing potential who are not willing/able to use effective methods of birth control (e.g., abstinence, oral contraceptives or implants, IUD, vaginal diaphragm or sponge, or condom with spermicide)
  • History of non-compliance to medical regimens and/or patients who are considered unreliable
  • History of bone metabolism diseases

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01129336

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Sponsors and Collaborators
Novartis Pharmaceuticals
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals

Additional Information:
Responsible Party: Novartis Pharmaceuticals Identifier: NCT01129336     History of Changes
Other Study ID Numbers: CZOL446EUS147
First Posted: May 24, 2010    Key Record Dates
Results First Posted: February 12, 2014
Last Update Posted: May 20, 2014
Last Verified: May 2014

Keywords provided by Novartis ( Novartis Pharmaceuticals ):
Metastatic breast cancer
First Line breast cancer
Second Line breast cancer
Breast cancer
Stage IV breast cancer
Progression free survival
Circulating Tumor Cells
Zoledronic acid
HER2-negative metastatic breast cancer patients without bone metastasis

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasm Metastasis
Bone Neoplasms
Bone Marrow Diseases
Neoplastic Cells, Circulating
Neoplasms by Site
Breast Diseases
Skin Diseases
Neoplastic Processes
Pathologic Processes
Bone Diseases
Musculoskeletal Diseases
Hematologic Diseases
Zoledronic acid
Bone Density Conservation Agents
Physiological Effects of Drugs