First or Second Line HER2-negative Breast Cancer Clinical Trial
— MACS1295Official 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
| Verified date | May 2014 |
| Source | Novartis |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | United States: Food and Drug Administration |
| Study type | Interventional |
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.
| Status | Completed |
| Enrollment | 44 |
| Est. completion date | August 2012 |
| Est. primary completion date | August 2012 |
| Accepts healthy volunteers | No |
| Gender | Female |
| Age group | 18 Years and older |
| Eligibility |
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 |
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
| Country | Name | City | State |
|---|---|---|---|
| United States | Kaiser Permanente Medical Group Kaiser Permanente - Hawaii | Anaheim | California |
| United States | Hematology Oncology Centers of the Northern Rockies Hema Onc Ctr N. Rockies (4 | Billings | Montana |
| United States | Kootenai Medical Center Kootenai Medical Center | Coeur d'Alene | Idaho |
| United States | Hematology Oncology Center, Inc. | Elyria | Ohio |
| United States | Highlands Oncology Group | Fayetteville | Arkansas |
| United States | Florida Cancer Specialists DeptofFloridaCancerSpecialists | Fort Myers | Florida |
| United States | Milton S Hershey Medical Center Hershey Medical Center (4) | Hershey | Pennsylvania |
| United States | Clopton Clinic | Jonesboro | Arkansas |
| United States | Wilshire Oncology Medical Group | La Verne | California |
| United States | NYU Langone Arena Oncology | Lake Success | New York |
| United States | Lakeland Regional Cancer Center Dept. of Lakeland Regional | Lakeland | Florida |
| United States | Southeast Nebraska Oncology Cancer Center | Lincoln | Nebraska |
| United States | Hematology Oncology Services of Arkansas | Little Rock | Arkansas |
| United States | Loma Linda University Loma Linda Cancer Center | Loma Linda | California |
| United States | The West Clinic | Memphis | Tennessee |
| United States | Sarah Cannon Research Institute | Nashville | Tennessee |
| United States | Oncology Specialists, SC Lutheran General Cancer Instit | Park Ridge | Illinois |
| United States | Reno Oncology Consultants | Reno | Nevada |
| United States | Medical Oncology & Hematology Associates of Northern VA Med. Onc&Hem Assoc. of No.VA | Reston | Virginia |
| United States | South Texas Oncology and Hematology, PA South Texas Oncology (2) | San Antonio | Texas |
| United States | Somerset Hematology Oncology Associates Somerset Hema Oncol Assoc (2) | Somerset | New Jersey |
| United States | St. John's Mercy Medical Center St. John's Mercy Med Ctr | St. Louis | Missouri |
| United States | Park Nicollet Institute Dept. of Park Nicollet | St. Louis Park | Minnesota |
| United States | Northwest Medical Specialties | Tacoma | Washington |
| United States | Space Coast Medical Associates | Titusville | Florida |
| United States | East Texas Medical Center Cancer Institute Tyler Hem/Onc (3) | Tyler | Texas |
| United States | Cooper Cancer Center | Voorhees | New Jersey |
| United States | Marion L. Shepard Cancer Center | Washington | North Carolina |
| United States | Hematology and Medical Oncology | Waterbury | Connecticut |
| United States | Berks Hematology Oncology | West Reading | Pennsylvania |
| United States | Abington Hematology Oncology Associates, Inc | Willow Grove | Pennsylvania |
| United States | Piedmont Hematology and Oncology Associates Piedmont Hem/Onc Assoc (2) | Winston-Salem | North Carolina |
| United States | Cancer Center of Kansas | Witchita | Kansas |
| Lead Sponsor | Collaborator |
|---|---|
| Novartis Pharmaceuticals |
United States,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | 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 | No |
| Secondary | 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). | Baseline, Month 1, 2, 4, 6, 9 and 18 | No |
| Secondary | 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. | up to 18 months | No |
| Secondary | 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. | Baseline, Month 2, Month 4 | No |