First or Second Line HER2-negative Breast CancerPhase 4MACS1295NCT01129336
Effect of Zoledronic Acid as Anti-Cancer Treatment in Metastatic Breast Cancer Patients
A Phase 4 study testing Zoledronic acid and Standard Therapy in people with First or Second Line HER2-negative Breast Cancer and Metastatic Disease Without Bone Metastasis, run by Novartis Pharmaceuticals at 33 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- First or Second Line HER2-negative Breast Cancer, Metastatic Disease Without Bone Metastasis
- What is being tested?
- Zoledronic acid and Standard Therapy
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 44 participants
- Where
- 33 sitesUnited States
- Study dates
- Jun 2010to Aug 2012
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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:
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- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
33 sites in 1 country.
33 sites in 1 country
United States33 sites
Kaiser Permanente Medical Group Kaiser Permanente - Hawaii
Anaheim, California, 92807
Hematology Oncology Centers of the Northern Rockies Hema Onc Ctr N. Rockies (4
Billings, Montana, 59101
Kootenai Medical Center Kootenai Medical Center
Coeur d'Alene, Idaho, 83814
Hematology Oncology Center, Inc.
Elyria, Ohio, 44035
Highlands Oncology Group
Fayetteville, Arkansas, 72753
Florida Cancer Specialists DeptofFloridaCancerSpecialists
Fort Myers, Florida, 33901
Milton S Hershey Medical Center Hershey Medical Center (4)
Hershey, Pennsylvania, 17033
Clopton Clinic
Jonesboro, Arkansas, 72401
Wilshire Oncology Medical Group
La Verne, California, 91750
NYU Langone Arena Oncology
Lake Success, New York, 11042
Lakeland Regional Cancer Center Dept. of Lakeland Regional
Lakeland, Florida, 33803
Southeast Nebraska Oncology Cancer Center
Lincoln, Nebraska, 68510
Hematology Oncology Services of Arkansas
Little Rock, Arkansas, 72205
Loma Linda University Loma Linda Cancer Center
Loma Linda, California, 92354
The West Clinic
Memphis, Tennessee, 38120
Sarah Cannon Research Institute
Nashville, Tennessee, 37203
Oncology Specialists, SC Lutheran General Cancer Instit
Park Ridge, Illinois, 60068-0736
Reno Oncology Consultants
Reno, Nevada, 89502
Medical Oncology & Hematology Associates of Northern VA Med. Onc&Hem Assoc. of No.VA
Reston, Virginia, 20190
Park Nicollet Institute Dept. of Park Nicollet
Saint Louis Park, Minnesota, 55416
South Texas Oncology and Hematology, PA South Texas Oncology (2)
San Antonio, Texas, 78258
Somerset Hematology Oncology Associates Somerset Hema Oncol Assoc (2)
Somerset, New Jersey, 08873
St. John's Mercy Medical Center St. John's Mercy Med Ctr
St Louis, Missouri, 63141
Northwest Medical Specialties
Tacoma, Washington, 98405
Space Coast Medical Associates
Titusville, Florida, 32796
East Texas Medical Center Cancer Institute Tyler Hem/Onc (3)
Tyler, Texas, 75701
Cooper Cancer Center
Voorhees Township, New Jersey, 08043
Marion L. Shepard Cancer Center
Washington, North Carolina, 27889
Hematology and Medical Oncology
Waterbury, Connecticut, 06708
Berks Hematology Oncology
West Reading, Pennsylvania, 19611
Abington Hematology Oncology Associates, Inc
Willow Grove, Pennsylvania, 19090
Piedmont Hematology and Oncology Associates Piedmont Hem/Onc Assoc (2)
Winston-Salem, North Carolina, 27103
Cancer Center of Kansas
Witchita, Kansas, 67214-3728
About this study
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
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
- Being tested
- Zoledronic acid, Standard Therapy
- 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
- Medical subject headings
- Breast Neoplasms, Neoplasm Metastasis, Neoplastic Cells, Circulating
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Zoledronic acidDrug
Also called Zometa, bisphosphonates, CZOL446E
Patients with no bone metastasis (n=150) will receive Standard therapy plus Zoledronic acid administration 4 mg IV monthly during Months 1-18.
Standard TherapyDrug
Standard Therapy, including chemotherapy and hormonal therapy, was determined at the discretion of the investigator.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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) Receives: Drug: Standard Therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
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).
Measured: Baseline, Month 1, 2, 4, 6, 9 and 18
Time to Progression (TTP)
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.
Measured: up to 18 months
Change From Baseline in Urine NTX by Month
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.
Measured: Baseline, Month 2, Month 4
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 May 2010 (estimated)
- Study startJun 2010
- Primary completionAug 2012
- Study completionAug 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for First or Second Line HER2-negative Breast CancerStudies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 44 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Novartis Pharmaceuticals, Study director, Novartis Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01129336
- Sponsor's protocol ID
- CZOL446EUS147
- Acronym
- MACS1295
- Status last verified
- May 2014
- First submitted
- 20 May 2010
- Last updated
- 20 May 2014
- Results posted
- Yes, on ClinicalTrials.gov
Study at a glance
From the registry record, last updated by the sponsor on 20 May 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01129336
- Acronym / sponsor ID
- MACS1295 / CZOL446EUS147
- 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
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 44 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- Jun 2010
- Primary completion
- Aug 2012 (actual)
- Study completion
- Aug 2012 (actual)
- First posted
- 24 May 2010 (estimated)
- Results
- Posted 12 Feb 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Patients without bone metastases | Experimental | Drug: Zoledronic acidPatients 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. |
| Patients with bone metastases | Experimental | Drug: Standard TherapyPatients with bone metastasis received standard therapy + zoledronic acid for 18 months (discontinued upon disease progression/secondary malignancy) |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- 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.
Key exclusion criteria (15 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Zoledronic acidAlso: Zometa, bisphosphonates, CZOL446EPatients with no bone metastasis (n=150) will receive Standard therapy plus Zoledronic acid administration 4 mg IV monthly during Months 1-18. | Drug | Patients without bone metastases |
| Standard TherapyStandard Therapy, including chemotherapy and hormonal therapy, was determined at the discretion of the investigator. | Drug | Patients with bone metastases |
Primary outcome
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.
3 secondary outcomes
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
Time to Progression (TTP)
Time frame: up to 18 months
Change From Baseline in Urine NTX by Month
Time frame: Baseline, Month 2, Month 4
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 May 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Related InfoLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Novartis Pharmaceuticals study director
Novartis Pharmaceuticals
33 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Zoledronic acid and Standard Therapy in people with First or Second Line HER2-negative Breast Cancer and Metastatic Disease Without Bone Metastasis, run by Novartis Pharmaceuticals at 33 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 20 May 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 33 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 12 Feb 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Progression Free Survival (PFS) (time frame: up to 18 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 May 2014.