Study Evaluating Efficacy And Tolerability Of Veliparib in Combination With Temozolomide (TMZ) or In Combination With Carboplatin and Paclitaxel Versus Placebo in Participants With Breast Cancer Gene (BRCA)1 and BRCA2 Mutation and Metastatic Breast Cancer
- Conditions
- Metastatic Breast Cancer
- Interventions
- Registration Number
- NCT01506609
- Lead Sponsor
- AbbVie
- Brief Summary
The primary objective of the study is to assess the progression-free survival (PFS) of oral veliparib in combination with TMZ or in combination with carboplatin and paclitaxel compared to placebo plus carboplatin and paclitaxel in subjects with BRCA1 or BRCA2 mutation and locally recurrent or metastatic breast cancer.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 294
- Histologically or cytologically confirmed breast cancer that is either locally recurrent or metastatic.
- Locally recurrent disease must not be amenable to surgical resection or radiation with curative intent.
- Must have a documented deleterious Breast Cancer Gene BRCA1 or BRCA2 germline mutation.
- If Human Epidermal Growth Factor Receptor (HER2) positive, subjects must have received and progressed on at least one prior standard HER2 directed therapy or the subject must be ineligible to receive anti-HER2 therapy.
- Measurable or non-measurable (but radiologically evaluable) disease by RECIST (Response Evaluation Criteria in Solid Tumors) criteria 1.1.
- Eastern Cooperative Oncology Group (ECOG) Performance Score of 0-2.
- Subject must have adequate bone marrow, renal and hepatic function.
- Subject must not be pregnant or plan to conceive a child.
- Received anticancer agent(s) or an investigational agent within 21 days prior to C1D1, or radiotherapy within 28 days prior Cycle 1 Day 1.
- More than 2 prior lines of cytotoxic chemotherapy.
- Prior treatment of breast cancer with temozolomide, a platinum agent, or a Poly (ADP ribose) Polymerase (PARP) inhibitor.
- Prior taxane therapy for metastatic breast cancer.
- A history of or evidence of brain metastases or leptomeningeal disease.
- A history of uncontrolled seizure disorder.
- Pre-existing neuropathy from any cause in excess of Grade 1.
- Known history of allergic reaction to cremophor/paclitaxel.
- Clinical significant uncontrolled conditions, active infection, myocardial infarction, stroke, or transient ischemic attack, psychiatric illness/social situations that would limit compliance.
- Pregnant or breastfeeding.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo with Carboplatin and Paclitaxel Placebo Placebo BID Days 1 through 7 plus carboplatin target area under the curve (mg•min/mL) (AUC) 6 administered on Day 3 of each 21-day cycle and paclitaxel 175 mg/m\^2 administered on Day 3 of each 21-day cycle. Placebo with Carboplatin and Paclitaxel Carboplatin Placebo BID Days 1 through 7 plus carboplatin target area under the curve (mg•min/mL) (AUC) 6 administered on Day 3 of each 21-day cycle and paclitaxel 175 mg/m\^2 administered on Day 3 of each 21-day cycle. Veliparib with Temozolomide Veliparib Veliparib 40 mg twice daily (BID) Days 1 through 7 plus TMZ 150 to 200 mg/m\^2 QD Days 1 through 5 in each 28-day cycle. Veliparib with Temozolomide Temozolomide Veliparib 40 mg twice daily (BID) Days 1 through 7 plus TMZ 150 to 200 mg/m\^2 QD Days 1 through 5 in each 28-day cycle. Placebo with Carboplatin and Paclitaxel Paclitaxel Placebo BID Days 1 through 7 plus carboplatin target area under the curve (mg•min/mL) (AUC) 6 administered on Day 3 of each 21-day cycle and paclitaxel 175 mg/m\^2 administered on Day 3 of each 21-day cycle. Veliparib with Carboplatin and Paclitaxel Veliparib Veliparib 80 mg BID Days 1 through 7 plus carboplatin target AUC 6 administered on Day 3 of each 21-day cycle and paclitaxel 175 mg/m\^2 administered on Day 3 of each 21-day cycle. Veliparib with Carboplatin and Paclitaxel Carboplatin Veliparib 80 mg BID Days 1 through 7 plus carboplatin target AUC 6 administered on Day 3 of each 21-day cycle and paclitaxel 175 mg/m\^2 administered on Day 3 of each 21-day cycle. Veliparib with Carboplatin and Paclitaxel Paclitaxel Veliparib 80 mg BID Days 1 through 7 plus carboplatin target AUC 6 administered on Day 3 of each 21-day cycle and paclitaxel 175 mg/m\^2 administered on Day 3 of each 21-day cycle.
- Primary Outcome Measures
Name Time Method Progression-Free Survival (PFS) Radiographic evaluation every 9 weeks, clinical evaluation every cycle (data cutoff date: 04 March 2016); maximum duration of follow up for PFS was 34 months. PFS is defined as the number of months from the date the participant was randomized to the date of radiographic progression as determined by the central imaging center, or to the date of all cause deaths within 63 days of last tumor assessment if disease progression was not reached.
- Secondary Outcome Measures
Name Time Method Overall Survival (OS) From Cycle 1 Day 1 until participant's death or 3 years post discontinuation (data cutoff date: 04 March 2016); maximum duration of follow up for OS was 72 months. Time to death for a given participant was defined as the number of months from the day the participant is randomized to the date of the participant's death. All events of death were included, regardless of whether the event occurs while the participant was still taking study drug, or after the participant discontinued study drug. If a participant had not died, then the data will be censored at the date when the participant was last known to be alive.
Clinical Benefit Rate (CBR) at Week 18 Week 18 CBR: percentage of participants who were progression-free at 18 weeks, defined as complete response (CR), partial response (PR), stable disease (SD) or non-CR/non-disease progression (PD) per Response Evaluation Criteria in Solid Tumors \[RECIST\] 1.1.
CR: The disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 0 mm. PR: \>= 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters (SOD). PD: \>= 20% increase in the SOD of target lesions, taking as reference the smallest SOD recorded since the treatment started (baseline or after) or the appearance of \>=1 new lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest SOD since the treatment started (baseline or after).Objective Response Rate (ORR) Radiographic evaluation every 9 weeks, clinical evaluation every cycle (data cutoff date: 04 March 2016); maximum duration of follow up for ORR was 34 months. The objective response rate, defined as percentage of participants with a confirmed CR or PR based on RECIST 1.1 criteria. CR: The disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 0 mm. PR: \>= 30% decrease in the sum of diameters of target lesions, taking as reference the baseline SODs.
Change From Baseline at Week 18 in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Chemotherapy-Induced Peripheral Neuropathy Module (EORTC QLQ-CIPN20) Sensory Subscale Score Baseline, Week 18 EORTC QLQ-CIPN20 sensory subscale score was calculated following the standard scoring algorithm, transformed to a 0 (low quality of life) to 100 (best quality of life) scale. A positive change from baseline indicates improvement.
Trial Locations
- Locations (120)
Sunnybrook Health Sciences Ctr /ID# 77373
🇨🇦Toronto, Ontario, Canada
The Angeles Clinic and Researc /ID# 60743
🇺🇸Los Angeles, California, United States
University of Pennsylvania /ID# 60753
🇺🇸Philadelphia, Pennsylvania, United States
University of Pittsburgh MC /ID# 65486
🇺🇸Pittsburgh, Pennsylvania, United States
University of Arkansas for Medical Sciences /ID# 60750
🇺🇸Little Rock, Arkansas, United States
Poltava Regional Clinical Oncology Centre of Poltava Regional Council /ID# 97697
🇺🇦Poltava, Ukraine
Skanes Universitetssjukhus /ID# 96475
🇸🇪Malmö, Skane Lan, Sweden
Hospital Universitario Vall d'Hebron /ID# 97415
🇪🇸Barcelona, Spain
Cherkassy Regional Onc Ctr /ID# 97698
🇺🇦Cherkasy, Ukraine
Odessa National Medical Univ /ID# 65278
🇺🇦Odesa, Ukraine
N.N. Petrov Research Inst Onc /ID# 78973
🇷🇺St. Petersburg, Russian Federation
Municipal Non-Profit Enterprise City Clinical Hospital No.4 of Dnipro City Counc /ID# 63940
🇺🇦Dnipro, Ukraine
Hospital Universitario Virgen de la Victoria /ID# 97976
🇪🇸Malaga, Spain
Hospital Santa Creu i Sant Pau /ID# 97418
🇪🇸Barcelona, Spain
Municipal Non-Profit Enterprise of Sumy Regional Council Sumy Regional Clinical /ID# 65280
🇺🇦Sumy, Ukraine
N.N. Petrov Research Inst Onc /ID# 65269
🇷🇺St. Petersburg, Russian Federation
Sahlgrenska University Hosp /ID# 97715
🇸🇪Goteborg, Sweden
Hospital Universitario HM Sanchinarro /ID# 97416
🇪🇸Madrid, Spain
Hospital Clinico Universitario de Valencia /ID# 97975
🇪🇸Valencia, Spain
Volgograd Reg Onc Disp #3 /ID# 98035
🇷🇺Volzhsky, Russian Federation
Karolinska Univ Sjukhuset /ID# 98037
🇸🇪Solna, Sweden
Communal non-profit enterprise Regional Center of Oncology /ID# 97696
🇺🇦Kharkiv, Ukraine
Lviv Oncological Regional Therapeutical and Diagnostic Centre /ID# 63941
🇺🇦Lviv, Ukraine
Hospital General Universitario Gregorio Maranon /ID# 97417
🇪🇸Madrid, Spain
Rush University Medical Center /ID# 65489
🇺🇸Chicago, Illinois, United States
Massachusetts General Hospital /ID# 64582
🇺🇸Boston, Massachusetts, United States
Dana-Farber Cancer Institute /ID# 93833
🇺🇸Boston, Massachusetts, United States
Irmandade da Santa Casa de /ID# 65244
🇧🇷Porto Alegre, Rio Grande Do Sul, Brazil
Hospital Bruno Born / Sociedade Beneficencia e Caridade de Lajeado /ID# 65247
🇧🇷Lajeado, Rio Grande Do Sul, Brazil
Mount Hospital /ID# 65262
🇦🇺Perth, Western Australia, Australia
Hospital de Clinicas de Porto Alegre /ID# 65242
🇧🇷Porto Alegre, Rio Grande Do Sul, Brazil
Duke University Medical Center /ID# 60747
🇺🇸Durham, North Carolina, United States
Grand Hôpital de Charleroi /ID# 96136
🇧🇪Charleroi, Hainaut, Belgium
Debreceni Egyetem Klinikai Kozpont /ID# 65178
🇭🇺Debrecen, Hungary
Bajcsy-Zsilinszky Korhaz /ID# 65179
🇭🇺Budapest, Hungary
Institut de Cancer de l'Ouest /ID# 63927
🇫🇷St Herblain CEDEX, Loire-Atlantique, France
NZOZ Centrum Medyczne HCP /ID# 68102
🇵🇱Poznan, Poland
Hopital Universitaire Purpan /ID# 98815
🇫🇷Toulouse, Haute-Garonne, France
Jasz-Nagykun-Szolnok Megyei Hetenyi Geza Korhaz /ID# 63928
🇭🇺Szolnok, Hungary
S.C. lanuli Med Consult SRL /ID# 106955
🇷🇴Bucharest, Romania
Inst Oncology Prof. Chiricuta /ID# 96740
🇷🇴Cluj, Romania
Centre Paul Strauss /ID# 100275
🇫🇷Strasbourg, France
Birch A Healthcare /ID# 65265
🇷🇺St. Petersburg, Russian Federation
Univ of Colorado Cancer Center /ID# 60751
🇺🇸Aurora, Colorado, United States
University of Pittsburgh MC /ID# 60758
🇺🇸Pittsburgh, Pennsylvania, United States
University of Illinois - Chicago /ID# 106175
🇺🇸Chicago, Illinois, United States
Moffitt Cancer Center /ID# 60746
🇺🇸Tampa, Florida, United States
University of Alabama at Birmingham - Main /ID# 62994
🇺🇸Birmingham, Alabama, United States
Moore UC San Diego Cancer Center /ID# 60754
🇺🇸La Jolla, California, United States
Banner MD Anderson Cancer Ctr /ID# 118695
🇺🇸Gilbert, Arizona, United States
Lynn Cancer Institute, Boca /ID# 60749
🇺🇸Boca Raton, Florida, United States
Cedars-Sinai Medical Center - West Hollywood /ID# 60760
🇺🇸West Hollywood, California, United States
Stanford University School of Med /ID# 65488
🇺🇸Stanford, California, United States
Holy Cross Hospital /ID# 62995
🇺🇸Fort Lauderdale, Florida, United States
Florida Cancer Specialists - East /ID# 60762
🇺🇸West Palm Beach, Florida, United States
Northwestern University Feinberg School of Medicine /ID# 60755
🇺🇸Chicago, Illinois, United States
Midwestern Regional CTC /ID# 60744
🇺🇸Zion, Illinois, United States
Johns Hopkins University /ID# 60759
🇺🇸Baltimore, Maryland, United States
Beth Israel Medical Center /ID# 87993
🇺🇸New York, New York, United States
William Beaumont Hospital /ID# 95417
🇺🇸Royal Oak, Michigan, United States
Washington University-School of Medicine /ID# 62724
🇺🇸Saint Louis, Missouri, United States
Memorial Sloan Kettering Cancer Center-Koch Center /ID# 63222
🇺🇸New York, New York, United States
Medical University of South Carolina /ID# 60752
🇺🇸Charleston, South Carolina, United States
Penn State University and Milton S. Hershey Medical Center /ID# 62723
🇺🇸Hershey, Pennsylvania, United States
The West Clinic /ID# 65487
🇺🇸Memphis, Tennessee, United States
The West Clinic /ID# 94599
🇺🇸Memphis, Tennessee, United States
The West Clinic /ID# 94600
🇺🇸Memphis, Tennessee, United States
Houston Methodist Hospital - Scurlock Tower /ID# 60742
🇺🇸Houston, Texas, United States
UT Southwestern Medical Center /ID# 60745
🇺🇸Dallas, Texas, United States
The Prince of Wales Hospital /ID# 63271
🇦🇺Randwick, New South Wales, Australia
Coiba /Id# 65219
🇦🇷Berazategui, Buenos Aires, Argentina
ISIS Centro Especializado /ID# 65226
🇦🇷Santa Fe, Argentina
Southern Medical Day Care Ctr /ID# 63274
🇦🇺Wollongong, New South Wales, Australia
Mater Misericordiae Limited /ID# 63276
🇦🇺South Brisbane, Queensland, Australia
Royal Hobart Hospital /ID# 63279
🇦🇺Hobart, Tasmania, Australia
Royal Adelaide Hospital /ID# 63280
🇦🇺Adelaide, South Australia, Australia
Peter MacCallum Cancer Ctr /ID# 63272
🇦🇺Melbourne, Victoria, Australia
Royal Melbourne Hospital /ID# 63278
🇦🇺Parkville, Victoria, Australia
UZ Antwerp /ID# 96945
🇧🇪Edegem, Belgium
Cliniques Universitaires Saint Luc /ID# 96135
🇧🇪Woluwe-Saint-Lambert, Bruxelles-Capitale, Belgium
AZ St-Jan Brugge-Oostende AV /ID# 107315
🇧🇪Brugge, West-Vlaanderen, Belgium
CHU UCL Namur /ID# 110595
🇧🇪Namur, Belgium
Jewish General Hospital /ID# 69893
🇨🇦Montreal, Quebec, Canada
CHUM - Notre-Dame Hospital /ID# 67862
🇨🇦Montréal, Quebec, Canada
CHUQ-Hospital St. Sacrement /ID# 68902
🇨🇦Quebec City, Quebec, Canada
Masarykuv onkologicky ustav /ID# 65170
🇨🇿Brno, Czechia
Palacky University /ID# 63923
🇨🇿Olomouc, Czechia
Vseobecna Fakultni Nemocnice /ID# 65172
🇨🇿Prague, Czechia
Rigshospitalet, Finsen Centre /ID# 67822
🇩🇰Copenhagen, Denmark
Vejle Sygehus /ID# 65173
🇩🇰Vejle, Syddanmark, Denmark
Tampere University Hospital /ID# 102417
🇫🇮Tampere, Finland
Docrates Cancer Center /ID# 63924
🇫🇮Helsinki, Finland
Institut Paoli-Calmettes /ID# 65175
🇫🇷Marseille, France
Centre Leon Berard /ID# 106675
🇫🇷Lyon CEDEX 08, Rhone, France
Institut Curie /ID# 63926
🇫🇷Paris CEDEX 05, Ile-de-France, France
Pays-Basque Ctr Oncology/Radio /ID# 65176
🇫🇷Bayonne, France
Hopital Rene Huguenin /ID# 65177
🇫🇷Saint-cloud, France
Soroka University Medical Center /ID# 65180
🇮🇱Be'er Sheva, Israel
Rambam Health Care Campus /ID# 63930
🇮🇱Haifa, Israel
Assaf Harofeh Medical Center /ID# 65181
🇮🇱Be'er Ya'akov, Israel
Rabin Medical Center /ID# 63929
🇮🇱Petakh Tikva, Tel-Aviv, Israel
Gastroenterology Institute, Division of Medicine /ID# 63931
🇮🇱Jerusalem, Israel
Shaare Zedek Medical Center /ID# 116575
🇮🇱Jerusalem, Israel
Kaplan Medical Center /ID# 63933
🇮🇱Rehovot, Israel
Sheba Medical Center /ID# 63932
🇮🇱Ramat Gan, Israel
Haukeland University Hospital /ID# 67982
🇳🇴Bergen, Hordaland, Norway
Erasmus Medisch Centrum /ID# 96275
🇳🇱Rotterdam, Netherlands
Mrukmed. Lekarz Beata Madej Mruk i Partner /ID# 94975
🇵🇱Rzeszów, Podkarpackie, Poland
Centrum Onkologii Lukaszczyka /ID# 73393
🇵🇱Bydgoszcz, Poland
Olsztynski Osrodek Onkologi /ID# 71060
🇵🇱Olsztyn, Poland
Wielkopolskie Centrum Onkologi /ID# 71061
🇵🇱Poznan, Poland
lnstitutul Oncologic Trestiore /ID# 96742
🇷🇴Bucharest, Romania
Spitalul Clinic Judetean de Urgenta /ID# 96741
🇷🇴Cluj, Romania
Sc Oncolab Srl /Id# 96745
🇷🇴Craiova, Romania
Chelyabinsk Reg Clin Oncology /ID# 63938
🇷🇺Chelyabinsk, Russian Federation
State Regional Budgetary Healthcare Institution " Murmansk Regional Oncology Dis /ID# 102415
🇷🇺Murmansk, Russian Federation
Federal State Budgetary Scientific Institution N.N. Blokhin Russian Cancer Resea /ID# 65263
🇷🇺Moscow, Moskva, Russian Federation
City Clinical Hospital 1 /ID# 102416
🇷🇺Novosibirsk, Russian Federation
Pyatigorsk Oncology Dispensary /ID# 65264
🇷🇺Pyatigorsk, Russian Federation
UZ Leuven /ID# 96138
🇧🇪Leuven, Belgium