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

Phase 4

Completed

Conditions: First or Second Line HER2-negative Breast Cancer
Metastatic Disease Without Bone Metastasis

Interventions: Drug: Standard Therapy
Drug: Zoledronic acid

Registration Number: NCT01129336

Lead Sponsor: 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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: Female

Target Recruitment: 44

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Patients with bone metastases	Standard Therapy	Patients with bone metastasis received standard therapy + zoledronic acid for 18 months (discontinued upon disease progression/secondary malignancy)
Patients without bone metastases	Zoledronic acid	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.

Primary Outcome Measures

Name	Time	Method
Number of Participants With Progression Free Survival (PFS)	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

Name	Time	Method
Percentage of Patients With Circulating Tumor Cell Levels of at Least 5 Per 7.5 mL of Peripheral Blood by Month	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).
Time to Progression (TTP)	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.
Change From Baseline in Urine NTX by Month	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.

Trial Locations

Locations (33): Loma Linda University Loma Linda Cancer Center
🇺🇸
Loma Linda, California, United States
Wilshire Oncology Medical Group
🇺🇸
La Verne, California, United States
Florida Cancer Specialists DeptofFloridaCancerSpecialists
🇺🇸
Fort Myers, Florida, United States
Hematology and Medical Oncology
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Waterbury, Connecticut, United States
Space Coast Medical Associates
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Titusville, Florida, United States
The West Clinic
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Memphis, Tennessee, United States
Northwest Medical Specialties
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Tacoma, Washington, United States
Lakeland Regional Cancer Center Dept. of Lakeland Regional
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Lakeland, Florida, United States
Hematology Oncology Services of Arkansas
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Little Rock, Arkansas, United States
Highlands Oncology Group
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Fayetteville, Arkansas, United States
Sarah Cannon Research Institute
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Nashville, Tennessee, United States
South Texas Oncology and Hematology, PA South Texas Oncology (2)
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San Antonio, Texas, United States
Abington Hematology Oncology Associates, Inc
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Willow Grove, Pennsylvania, United States
East Texas Medical Center Cancer Institute Tyler Hem/Onc (3)
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Tyler, Texas, United States
Cancer Center of Kansas
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Witchita, Kansas, United States
Hematology Oncology Center, Inc.
🇺🇸
Elyria, Ohio, United States
Marion L. Shepard Cancer Center
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Washington, North Carolina, United States
Clopton Clinic
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Jonesboro, Arkansas, United States
Kaiser Permanente Medical Group Kaiser Permanente - Hawaii
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Anaheim, California, United States
Kootenai Medical Center Kootenai Medical Center
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Coeur d'Alene, Idaho, United States
Oncology Specialists, SC Lutheran General Cancer Instit
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Park Ridge, Illinois, United States
Park Nicollet Institute Dept. of Park Nicollet
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St. Louis Park, Minnesota, United States
St. John's Mercy Medical Center St. John's Mercy Med Ctr
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St. Louis, Missouri, United States
Hematology Oncology Centers of the Northern Rockies Hema Onc Ctr N. Rockies (4
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Billings, Montana, United States
Southeast Nebraska Oncology Cancer Center
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Lincoln, Nebraska, United States
Cooper Cancer Center
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Voorhees, New Jersey, United States
Somerset Hematology Oncology Associates Somerset Hema Oncol Assoc (2)
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Somerset, New Jersey, United States
NYU Langone Arena Oncology
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Lake Success, New York, United States
Piedmont Hematology and Oncology Associates Piedmont Hem/Onc Assoc (2)
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Winston-Salem, North Carolina, United States
Milton S Hershey Medical Center Hershey Medical Center (4)
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Hershey, Pennsylvania, United States
Berks Hematology Oncology
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West Reading, Pennsylvania, United States
Reno Oncology Consultants
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Reno, Nevada, United States
Medical Oncology & Hematology Associates of Northern VA Med. Onc&Hem Assoc. of No.VA
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Reston, Virginia, United States