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

NCT01129336 | Completed Phase 4 Results

• 1 other identifier: CZOL446EUS147
• Study Type: interventional
• Target: 44
• Locations: 1 country
• Sites: 33

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.

Conditions

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

Keywords

HER2-negative; HER2; Metastatic breast cancer; First Line breast cancer; Second Line breast cancer; Breast cancer; Metastatic; Stage IV breast cancer; Progression free survival; PFS; Circulating Tumor Cells; CTCs; Zoledronic acid; HER2-negative metastatic breast cancer patients without bone metastasis

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Progression Free Survival (PFS)

  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.

  up to 18 months

Secondary Outcomes (3)

• 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

• Time to Progression (TTP)

  up to 18 months

• Change From Baseline in Urine NTX by Month

  Baseline, Month 2, Month 4

Study Arms (2)

Patients without bone metastases

EXPERIMENTAL

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 bone metastases

EXPERIMENTAL

Patients with bone metastasis received standard therapy + zoledronic acid for 18 months (discontinued upon disease progression/secondary malignancy)

Drug: Standard Therapy

Interventions

Zoledronic acid DRUG

Patients with no bone metastasis (n=150) will receive Standard therapy plus Zoledronic acid administration 4 mg IV monthly during Months 1-18.

Also known as: Zometa, bisphosphonates, CZOL446E

Patients without bone metastases

Standard Therapy DRUG

Standard Therapy, including chemotherapy and hormonal therapy, was determined at the discretion of the investigator.

Patients with bone metastases

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• no sign of clinical progression or known progression of brain metastasis
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (33)

Highlands Oncology Group

Fayetteville, Arkansas, 72753, United States

Location

Clopton Clinic

Jonesboro, Arkansas, 72401, United States

Location

Hematology Oncology Services of Arkansas

Little Rock, Arkansas, 72205, United States

Location

Kaiser Permanente Medical Group Kaiser Permanente - Hawaii

Anaheim, California, 92807, United States

Location

Wilshire Oncology Medical Group

La Verne, California, 91750, United States

Location

Loma Linda University Loma Linda Cancer Center

Loma Linda, California, 92354, United States

Location

Hematology and Medical Oncology

Waterbury, Connecticut, 06708, United States

Location

Florida Cancer Specialists DeptofFloridaCancerSpecialists

Fort Myers, Florida, 33901, United States

Location

Lakeland Regional Cancer Center Dept. of Lakeland Regional

Lakeland, Florida, 33803, United States

Location

Space Coast Medical Associates

Titusville, Florida, 32796, United States

Location

Kootenai Medical Center Kootenai Medical Center

Coeur d'Alene, Idaho, 83814, United States

Location

Oncology Specialists, SC Lutheran General Cancer Instit

Park Ridge, Illinois, 60068-0736, United States

Location

Cancer Center of Kansas

Witchita, Kansas, 67214-3728, United States

Location

Park Nicollet Institute Dept. of Park Nicollet

Saint Louis Park, Minnesota, 55416, United States

Location

St. John's Mercy Medical Center St. John's Mercy Med Ctr

St Louis, Missouri, 63141, United States

Location

Hematology Oncology Centers of the Northern Rockies Hema Onc Ctr N. Rockies (4

Billings, Montana, 59101, United States

Location

Southeast Nebraska Oncology Cancer Center

Lincoln, Nebraska, 68510, United States

Location

Reno Oncology Consultants

Reno, Nevada, 89502, United States

Location

Somerset Hematology Oncology Associates Somerset Hema Oncol Assoc (2)

Somerset, New Jersey, 08873, United States

Location

Cooper Cancer Center

Voorhees Township, New Jersey, 08043, United States

Location

NYU Langone Arena Oncology

Lake Success, New York, 11042, United States

Location

Marion L. Shepard Cancer Center

Washington, North Carolina, 27889, United States

Location

Piedmont Hematology and Oncology Associates Piedmont Hem/Onc Assoc (2)

Winston-Salem, North Carolina, 27103, United States

Location

Hematology Oncology Center, Inc.

Elyria, Ohio, 44035, United States

Location

Milton S Hershey Medical Center Hershey Medical Center (4)

Hershey, Pennsylvania, 17033, United States

Location

Berks Hematology Oncology

West Reading, Pennsylvania, 19611, United States

Location

Abington Hematology Oncology Associates, Inc

Willow Grove, Pennsylvania, 19090, United States

Location

The West Clinic

Memphis, Tennessee, 38120, United States

Location

Sarah Cannon Research Institute

Nashville, Tennessee, 37203, United States

Location

South Texas Oncology and Hematology, PA South Texas Oncology (2)

San Antonio, Texas, 78258, United States

Location

East Texas Medical Center Cancer Institute Tyler Hem/Onc (3)

Tyler, Texas, 75701, United States

Location

Medical Oncology & Hematology Associates of Northern VA Med. Onc&Hem Assoc. of No.VA

Reston, Virginia, 20190, United States

Location

Northwest Medical Specialties

Tacoma, Washington, 98405, United States

Location

Related Links

• Related Info

MeSH Terms

Conditions

Breast Neoplasms; Neoplasm Metastasis; Neoplastic Cells, Circulating

Interventions

Zoledronic Acid; Diphosphonates; Standard of Care

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Organophosphonates; Organophosphorus Compounds; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

862-778-8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 20, 2010
• First Posted: May 24, 2010
• Study Start: June 1, 2010
• Primary Completion: August 1, 2012
• Study Completion: August 1, 2012
• Last Updated: May 20, 2014
• Results First Posted: February 12, 2014

Record last verified: 2014-05

Locations

US (33)