Metastatic Breast Cancer Clinical Trial
— BOLERO-3Official title:
A Randomized Phase III, Double-blind, Placebo-controlled Multicenter Trial of Daily Everolimus in Combination With Trastuzumab and Vinorelbine, in Pretreated Women With HER2/Neu Over-expressing Locally Advanced or Metastatic Breast Cancer.
| Verified date | October 2015 |
| Source | Novartis |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | United States: Food and Drug Administration |
| Study type | Interventional |
This phase III, double-blind, placebo-controlled multinational study will assess the combination everolimus, vinorelbine, and trastuzumab compared to the combination vinorelbine and trastuzumab with respect to progressive-free survival and over survival in HER2/neu positive women with locally advanced or metastatic breast cancer who are resistant to trastuzumab and have been pre-treated with a taxane.
| Status | Completed |
| Enrollment | 570 |
| Est. completion date | June 2015 |
| Est. primary completion date | June 2015 |
| Accepts healthy volunteers | No |
| Gender | Female |
| Age group | 18 Years and older |
| Eligibility |
Inclusion Criteria: - Histologically or cytologically confirmed invasive breast carcinoma with locally recurrent or radiological evidence of metastatic disease. Locally recurrent disease must not be amenable to resection with curative intent. - HER2+ status defined as IHC 3+ staining or in situ hybridization positive - Patients with resistance to trastuzumab - Prior taxane therapy - Patients with an ECOG performance status of 0 - 2 - Patients with measurable disease as per RECIST criteria - Documentation of negative pregnancy test for patients of child bearing potential prior to enrollment within 7 days prior to randomization. Sexually active pre-menopausal women must use adequate contraceptive measures, excluding estrogen containing contraceptives, while on study; - Patients must meet laboratory criteria defined in the study within 21 days prior to randomization Exclusion Criteria: - Prior mTOR inhibitors or vinca alkaloid agents for the treatment of cancer - More than three prior chemotherapy lines for advanced disease. - Symptomatic CNS metastases or evidence of leptomeningeal disease. Previously treated asymptomatic CNS metastases are allowed provided that the last treatment for CNS metastases was completed >8 weeks prior to randomization - Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral everolimus - Peripheral neuropathy = grade 2 at randomization - Active cardiac disease - History of cardiac dysfunction - Any malignancy within 5 years prior to randomization, with the exception of adequately treated in-situ carcinoma of the cervix uteri, basal or squamous cell carcinoma or non-melanomatous skin cancer - Known hypersensitivity to any study medication - Breastfeeding or pregnant Other protocol-defined inclusion/exclusion criteria may ap |
Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment
| Country | Name | City | State |
|---|---|---|---|
| Argentina | Novartis Investigative Site | Buenos Aires | |
| Argentina | Novartis Investigative Site | C A B A | Buenos Aires |
| Argentina | Novartis Investigative Site | Cordoba | |
| Argentina | Novartis Investigative Site | Mar del Plata | Buenos Aires |
| Argentina | Novartis Investigative Site | Posadas | Misiones |
| Argentina | Novartis Investigative Site | Quilmes | Buenos Aires |
| Argentina | Novartis Investigative Site | Rio Negro | Viedma |
| Argentina | Novartis Investigative Site | Rosario | Sante Fe |
| Argentina | Novartis Investigative Site | Tucuman | |
| Australia | Novartis Investigative Site | East Bentleigh | Victoria |
| Australia | Novartis Investigative Site | Hobart | Tasmania |
| Australia | Novartis Investigative Site | Kogarah | New South Wales |
| Australia | Novartis Investigative Site | South Brisbane | Queensland |
| Australia | Novartis Investigative Site | Southport | Queensland |
| Australia | Novartis Investigative Site | St. Leonards | New South Wales |
| Belgium | Novartis Investigative Site | Brussel | |
| Belgium | Novartis Investigative Site | Bruxelles | |
| Belgium | Novartis Investigative Site | Liège | |
| Belgium | Novartis Investigative Site | Luxembourg | |
| Belgium | Novartis Investigative Site | Namur | |
| Belgium | Novartis Investigative Site | Sint-Niklaas | |
| China | Novartis Investigative Site | Beijing | |
| China | Novartis Investigative Site | Beijing | |
| China | Novartis Investigative Site | Guangzhou | |
| China | Novartis Investigative Site | Hangzhou | Zhejiang |
| China | Novartis Investigative Site | Shanghai | Shanghai |
| China | Novartis Investigative Site | Shanghai | |
| Czech Republic | Novartis Investigative Site | Novy Jicin | |
| Czech Republic | Novartis Investigative Site | Olomouc | |
| Czech Republic | Novartis Investigative Site | Prague 5 | |
| France | Novartis Investigative Site | Bayonne | |
| France | Novartis Investigative Site | Besançon cedex | |
| France | Novartis Investigative Site | Hyères | |
| France | Novartis Investigative Site | La Chaussée St Victor | |
| France | Novartis Investigative Site | La Roche sur Yon Cedex | |
| France | Novartis Investigative Site | Nice Cedex 2 | |
| France | Novartis Investigative Site | Saint-Brieuc Cédex | |
| France | Novartis Investigative Site | Villejuif Cedex | |
| Germany | Novartis Investigative Site | Berlin | |
| Germany | Novartis Investigative Site | Frankfurt | |
| Germany | Novartis Investigative Site | Gerlingen | |
| Germany | Novartis Investigative Site | Halle/'Saale | |
| Germany | Novartis Investigative Site | Hamburg | |
| Germany | Novartis Investigative Site | Homburg | |
| Germany | Novartis Investigative Site | Kiel | |
| Germany | Novartis Investigative Site | Magdeburg | |
| Germany | Novartis Investigative Site | Mainz | |
| Germany | Novartis Investigative Site | Minden | |
| Germany | Novartis Investigative Site | München | |
| Germany | Novartis Investigative Site | Recklinghausen | |
| Germany | Novartis Investigative Site | Velbert | |
| Greece | Novartis Investigative Site | Athens, Neo Faliro | |
| Greece | Novartis Investigative Site | Heraklion Crete | GR |
| Greece | Novartis Investigative Site | Patra - RIO | GR |
| Greece | Novartis Investigative Site | Thessaloniki | GR |
| Greece | Novartis Investigative Site | Thessaloniki | GR |
| Hungary | Novartis Investigative Site | Budapest | |
| Hungary | Novartis Investigative Site | Budapest | |
| Hungary | Novartis Investigative Site | Debrecen | |
| Hungary | Novartis Investigative Site | Gyor | |
| Israel | Novartis Investigative Site | Jerusalem | |
| Israel | Novartis Investigative Site | Petach Tikva | |
| Israel | Novartis Investigative Site | Ramat Gan | |
| Israel | Novartis Investigative Site | Tel-Aviv | |
| Italy | Novartis Investigative Site | Catania | CT |
| Italy | Novartis Investigative Site | Milano | MI |
| Italy | Novartis Investigative Site | Milano | MI |
| Italy | Novartis Investigative Site | Milano | MI |
| Italy | Novartis Investigative Site | Pavia | PV |
| Italy | Novartis Investigative Site | Sondrio | SO |
| Japan | Novartis Investigative Site | Bunkyo-ku | Tokyo |
| Japan | Novartis Investigative Site | Fukuoka | |
| Japan | Novartis Investigative Site | Kashiwa | Chiba |
| Japan | Novartis Investigative Site | Koto | Tokyo |
| Japan | Novartis Investigative Site | Kumamoto City | Kumamoto |
| Japan | Novartis Investigative Site | Kyoto-city | Kyoto |
| Japan | Novartis Investigative Site | Maebashi-city | Gunma |
| Japan | Novartis Investigative Site | Nagoya | Aichi |
| Japan | Novartis Investigative Site | Osaka | |
| Japan | Novartis Investigative Site | Osaka | |
| Japan | Novartis Investigative Site | Sapporo | Hokkaido |
| Japan | Novartis Investigative Site | Suita-city | Osaka |
| Japan | Novartis Investigative Site | Yokohama | Kanagawa |
| Mexico | Novartis Investigative Site | Ciudad De Mexico | Distrito Federal |
| Mexico | Novartis Investigative Site | León | Guanajuato |
| Poland | Novartis Investigative Site | Lublin | |
| Poland | Novartis Investigative Site | Warszawa | |
| Singapore | Novartis Investigative Site | Singapore | |
| Slovakia | Novartis Investigative Site | Bratislava | |
| Slovakia | Novartis Investigative Site | Kosice | |
| Spain | Novartis Investigative Site | A Coruna | Galicia |
| Spain | Novartis Investigative Site | Barcelona | Catalunya |
| Spain | Novartis Investigative Site | Barcelona | |
| Spain | Novartis Investigative Site | Cordoba | Andalucia |
| Spain | Novartis Investigative Site | Jaen | Andalucia |
| Spain | Novartis Investigative Site | La Coruna | Galicia |
| Spain | Novartis Investigative Site | La Laguna | Las Palmas de Gran Canaria |
| Spain | Novartis Investigative Site | Madrid | |
| Spain | Novartis Investigative Site | Madrid | |
| Spain | Novartis Investigative Site | Madrid | |
| Spain | Novartis Investigative Site | Majadanonda | Madrid |
| Spain | Novartis Investigative Site | Sabadell | Barcelona |
| Spain | Novartis Investigative Site | Sevilla | Andalucia |
| Spain | Novartis Investigative Site | Valencia | Comunidad Valenciana |
| Spain | Novartis Investigative Site | Zaragoza | |
| Thailand | Novartis Investigative Site | Bangkok | |
| Thailand | Novartis Investigative Site | Bangkok | |
| Turkey | Novartis Investigative Site | Ankara | |
| Turkey | Novartis Investigative Site | Istanbul | |
| Turkey | Novartis Investigative Site | Izmir | |
| United Kingdom | Novartis Investigative Site | Bournemouth | |
| United Kingdom | Novartis Investigative Site | Leeds | |
| United Kingdom | Novartis Investigative Site | London | |
| United Kingdom | Novartis Investigative Site | Manchester | |
| United Kingdom | Novartis Investigative Site | Plymouth | |
| United Kingdom | Novartis Investigative Site | Surrey | England |
| United Kingdom | Novartis Investigative Site | Truro | Cornwall |
| United States | Emory University School of Medicine/Winship Cancer Institute Dept.of WinshipCancerInst. (2) | Atlanta | Georgia |
| United States | Comprehensive Cancer Center - Boca Raton Deerfield Beach | Boca Raton | Florida |
| United States | Comprehensive Cancer Center - Boca Raton Dept.of BocaRatonCompCanCtr | Boca Raton | Florida |
| United States | Texas Cancer Center ( Medical City Dallas Hospital) Dept. of Texas Cancer Ctr. (2) | Dallas | Texas |
| United States | Texas Oncology, P.A. Midtown | Dallas | Texas |
| United States | Texas Oncology, P.A. Presbyterian Hospital (2) | Dallas | Texas |
| United States | Texas Oncology, P.A. Texas Onc - Amarillo | Dallas | Texas |
| United States | Texas Oncology, P.A. Texas Oncology - Sammons | Dallas | Texas |
| United States | University of Texas Southwestern Medical Center University of TX SW Med Ctr(2) | Dallas | Texas |
| United States | Duke University Medical Center Dept. of DUMC (2) | Durham | North Carolina |
| United States | North Shore University Health System NSU | Evanston | Illinois |
| United States | Virginia Cancer Specialists, PC Dept.ofFairfaxNo.VA (2) | Fairfax | Virginia |
| United States | Florida Cancer Specialists DeptofFloridaCancerSpecialists | Fort Myers | Florida |
| United States | The Jones Clinic Dept .of The Jones Clinic (3) | Germantown | Tennessee |
| United States | St Vincent Hospital Green Bay Oncology | Green Bay | Wisconsin |
| United States | Rocky Mountain Cancer Centers RMCC | Greenwood Village | Colorado |
| United States | Memorial Hospital Memorial Cancer Institute | Hollywood | Florida |
| United States | Baylor College of Medicine Baylor | Houston | Texas |
| United States | University of Texas/MD Anderson Cancer Center Dept of MD Anderson (17) | Houston | Texas |
| United States | University of California San Diego La Jolla - UCSD Moores Cancer | La Jolla | California |
| United States | NYU Langone Arena Oncology Dept.ofArenaOncologyAssoc(2) | Lake Success | New York |
| United States | Comprehensive Cancer Centers of Nevada CCC of Nevada Henderson (4) | Las Vegas | Nevada |
| United States | Nevada Cancer Institute Dept. of Nevada Cancer (3) | Las Vegas | Nevada |
| United States | Longview Cancer Center Longview Cancer Center (2) | Longview | Texas |
| United States | Sarah Cannon Research Institute Dept.ofSarahCannonCancerCtr(6) | Nashville | Tennessee |
| United States | Virginia Oncology Associates Dept. of VOA (2) | Norfolk | Virginia |
| United States | University of Nebraska Medical Center Unv Nebraska Med Ctr (2) | Omaha | Nebraska |
| United States | MD Anderson Cancer Center - Orlando Dept.ofMDACC-Orlando(2) | Orlando | Florida |
| United States | Kansas City Cancer Center KCCC- South (2) | Overland Park | Kansas |
| United States | Maryland Oncology Hematology | Owning Mills | Maryland |
| United States | University of Pittsburgh Cancer Institute DeptofMageeWomen'sHospital(2) | Pittsburgh | Pennsylvania |
| United States | Northwest Cancer Specialists Tutlatin | Portland | Oregon |
| United States | Utah Cancer Specialists Utah Cancer (2) | Salt Lake City | Utah |
| United States | Cancer Care Centers of South Texas / HOAST CCC of So. TX- San Antonio(2) | San Antonio | Texas |
| United States | South Texas Oncology and Hematology, PA South Texas Oncology (2) | San Antonio | Texas |
| United States | Swedish Cancer Institute Swedish Cancer Institute | Seattle | Washington |
| United States | St. Louis University Cancer Center SLU Cancer Center | St. Louis | Missouri |
| United States | Park Nicollet Institute Dept. of Park Nicollet | St. Louis Park | Minnesota |
| United States | Overlook Hospital - Carol G Simon Cancer Center Carol G Simon | Summit | New Jersey |
| United States | University of Arizona / Arizona Cancer Center AZ Onc Assoc | Tucson | Arizona |
| United States | University of Arizona / Arizona Cancer Center Deptof Uof A/Arizona Cancer(3) | Tucson | Arizona |
| United States | Tyler Cancer Center Dept.ofTylerCancerCtr. (2) | Tyler | Texas |
| United States | Georgetown University/Lombardi Cancer Center Dept.of Lombardi CancerCtr (3) | Washington | District of Columbia |
| Lead Sponsor | Collaborator |
|---|---|
| Novartis Pharmaceuticals |
United States, Argentina, Australia, Belgium, China, Czech Republic, France, Germany, Greece, Hungary, Israel, Italy, Japan, Mexico, Poland, Singapore, Slovakia, Spain, Thailand, Turkey, United Kingdom,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Progressive-free survival (PFS), defined as the time from the date of randomization to the date of first radiologically documented tumor progression or death from any cause, whichever occurs first. | Every 6 months | No | |
| Secondary | Overall survival (OS), defined as the time from date of randomization to the date of death from any cause. | Every 3 months | No | |
| Secondary | Overall response rate (ORR) defined as the proportion of patients whose best overall response is either complete response (CR) or partial response (PR) according to RECIST | Every 6 weeks | No | |
| Secondary | Patient reported outcome (PRO) questionnaires | Every 6 weeks | No | |
| Secondary | Clinical benefit rate (CBR) defined as the proportion of patients whose best overall response, according to RECIST, is either complete response (CR), a partial response (PR) or stable disease (SD) lasting for at least 24 weeks. | Every 6 weeks | No | |
| Secondary | Laboratory assessments (hematology, chemistry, coagulation), AEs graded by CTCAE version 3.0 or equivalent | Continuous until 28 days after the last dose of study drug | Yes |
| Status | Clinical Trial | Phase | |
|---|---|---|---|
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