The Study Evaluating Efficacy And Tolerability Of Veliparib in Combination With Temozolomide or In Combination With Carboplatin and Paclitaxel Versus Placebo in Subjects With BRCA1 and BRCA2 Mutation and Metastatic Breast Cancer

Study Description

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Brief Summary:

The Study Evaluating Efficacy And Tolerability of Veliparib in Combination with Temozolomide or Veliparib/Placebo in Combination with Carboplatin and Paclitaxel in Subjects with locally recurrent Breast Cancer not amenable to therapy with curative intent, or metastatic breast cancer and a documented (BRCA1) and (BRCA2) deleterious germline mutation.

Condition or disease	Intervention/treatment	Phase
Metastatic Breast Cancer	Drug: Placebo; Drug: Veliparib; Drug: Carboplatin; Drug: Temozolomide; Drug: Paclitaxel	Phase 2

Detailed Description:

Subjects will be randomized in a 1:1:1 ratio to one of the three treatment groups. The safety of each treatment group will be assessed by evaluating study drug exposure, adverse events, serious adverse events, all deaths, changes in laboratory determinations, and vital sign parameters. The Clinical Benefit Rate (CBR) and Objective Response Rate (ORR) as well as Progression-free survival (PFS) using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 will be assessed. Study visits will be conducted according to the protocol schedule and randomization group. Study visits will include physical examination, laboratory blood sample collection, and assessment of vital signs, medical history and urinalysis. 12-lead Electrocardiogram (ECG) will be performed at protocol specified visits.

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	294 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	Double (Participant, Investigator)
Primary Purpose:	Treatment
Official Title:	A Randomized, Phase 2 Study of the Efficacy and Tolerability of Veliparib in Combination With Temozolomide or Veliparib in Combination With Carboplatin and Paclitaxel Versus Placebo Plus Carboplatin and Paclitaxel in Subjects With BRCA1 or BRCA2 Mutation and Metastatic Breast Cancer
Actual Study Start Date :	January 23, 2012
Estimated Primary Completion Date :	August 10, 2018
Estimated Study Completion Date :	August 10, 2018

Arms and Interventions

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Arm	Intervention/treatment
Experimental: Veliparib with Temozolomide; Veliparib on Day 1 thru 7 and temozolomide on Day 1 thru 5 of a 28-day cycle.	Drug: Veliparib; Days 1 through 7 of 28-day cycle (in combination with Temozolomide) or Days 1 through 7 of 21-day cycle (in combination with Carboplatin and Paclitaxel).; Other Name: ABT-888 Drug: Temozolomide; Days 1 through 5 of 28-day cycle (in combination with veliparib).; Other Name: Temodal
Placebo Comparator: Placebo with Carboplatin and Paclitaxel; Placebo on Day 1 thru 7 and carboplatin/paclitaxel on Day 3 of a 21-day cycle.	Drug: Placebo; Placebo comparator for Veliparib days 1 through 7 of 21-day cycle (in combination with carboplatin and/or paclitaxel). Drug: Carboplatin; Day 3 of 21-day cycle Drug: Paclitaxel; Day 3 of 21-day cycle.; Other Name: Taxol
Experimental: Veliparib with Carboplatin and Paclitaxel; Veliparib on Day 1 thru 7 and carboplatin/paclitaxel on Day 3 of a 21-day cycle.	Drug: Veliparib; Days 1 through 7 of 28-day cycle (in combination with Temozolomide) or Days 1 through 7 of 21-day cycle (in combination with Carboplatin and Paclitaxel).; Other Name: ABT-888 Drug: Carboplatin; Day 3 of 21-day cycle Drug: Paclitaxel; Day 3 of 21-day cycle.; Other Name: Taxol

Outcome Measures

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Primary Outcome Measures :

1. Progression -Free Survival [ Time Frame: Radiographic evaluation every 9 weeks, clinical evaluation every cycle ]

Secondary Outcome Measures :

1. Overall Survival [ Time Frame: From Cycle 1 Day 1 until patient's death or 3 years post discontinuation ]
2. Clinical Benefit Rate (CBR) [ Time Frame: From Cycle 1 Day1 until patient's death or 3 years post discontinuation ]
3. Objective Response Rate [ Time Frame: From Cycle 1 Day 1 until patient's death or 3 years post discontinuation ]

Other Outcome Measures:

1. Chemotherapy-Induced Peripheral Neuropathy (CIPN) [ Time Frame: From Cycle 1 Day 1 for subjects on the carboplatin and paclitaxel treatment arm, through 30 Day Follow-up Visit. ]
   CIPN (as assessed by the EORTC QLQ-CIPN20 questionnaire and NCI-CTCAE 4.0 grading for peripheral neuropathy

Eligibility Criteria

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Ages Eligible for Study:	18 Years to 99 Years (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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 â€" active infection, myocardial infarction, stroke, or transient ischemic attack, psychiatric illness/social situations that would limit compliance.
• Pregnant or breastfeeding

Contacts and Locations

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Locations

United States, Alabama
University of Alabama
Birmingham, Alabama, United States, 35233
United States, Arizona
Banner MD Anderson Cancer Ctr
Gilbert, Arizona, United States, 85234
United States, Arkansas
Univ Arkansas Medical Sciences
Little Rock, Arkansas, United States, 72205
United States, California
Cedars-Sinai Medical Center
Beverly Hills, California, United States, 90211
The Angeles Clinic and Researc
Los Angeles, California, United States, 90025
Cedars-Sinai Medical Ctr
Los Angeles, California, United States, 90048
UCSD
San Diego, California, United States, 92122
Stanford Univ School of Med
Stanford, California, United States, 94305
United States, Colorado
Children's Hospital Colorado
Aurora, Colorado, United States, 80045
United States, Florida
Lynn Cancer Institute, Boca
Boca Raton, Florida, United States, 33486
Holy Cross Hospital
Fort Lauderdale, Florida, United States, 33308
Moffitt Cancer Center
Tampa, Florida, United States, 33612
Florida Cancer Specialists
West Palm Beach, Florida, United States, 33401
United States, Illinois
University of Illinois
Chicago, Illinois, United States, 60607
Northwestern University
Chicago, Illinois, United States, 60611
Rush Univ Med Ctr
Chicago, Illinois, United States, 60612
Midwestern Regional Med Ctr
Zion, Illinois, United States, 60099
United States, Maryland
Johns Hopkins
Baltimore, Maryland, United States, 21287
United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
Dana Farber Cancer Institute
Boston, Massachusetts, United States, 02215
United States, Michigan
William Beaumont Hospital
Royal Oak, Michigan, United States, 48073
United States, Missouri
Washington Univ School Med
Saint Louis, Missouri, United States, 63110
United States, New York
Beth Israel Medical Center
New York, New York, United States, 10003
Memorial Sloan-Kettering Cance
New York, New York, United States, 10065
United States, North Carolina
Duke Univ Med Ctr
Durham, North Carolina, United States, 27710
United States, Pennsylvania
Penn State, Milton Hershey Med
Hershey, Pennsylvania, United States, 17033
University of Pennsylvania
Philadelphia, Pennsylvania, United States, 19104
UPMC
Pittsburgh, Pennsylvania, United States, 15260
United States, South Carolina
Med Univ of South Carolina
Charleston, South Carolina, United States, 29425
United States, Tennessee
The West Clinic
Memphis, Tennessee, United States, 38120
United States, Texas
UT Southwestern Medical Center
Dallas, Texas, United States, 75235
The Methodist Hospital
Houston, Texas, United States, 77030
Argentina
COIBA
Berazategui, Buenos Aires, Argentina, 1884
ISIS Centro Especializado
Santa Fe, Argentina, 3000
Australia, New South Wales
The Prince of Wales Hospital
Randwick, New South Wales, Australia, 2031
Southern Medical Day Care Ctr
Wollongong, New South Wales, Australia, 2500
Australia, Queensland
Mater Health Hospital
South Brisbane, Queensland, Australia, 4101
Australia, South Australia
Royal Adelaide Hospital
Adelaide, South Australia, Australia, 5000
Australia, Tasmania
Royal Hobart Hospital
Hobart, Tasmania, Australia, 7000
Australia, Victoria
Peter MacCallum Cancer Ctr
Melbourne, Victoria, Australia, 3050
Royal Melbourne Hospital
Parkville, Victoria, Australia, 3050
Australia, Western Australia
Mount Hospital
Perth, Western Australia, Australia, 6000
Belgium
AZ St-Jan Brugge-Oostende AV
Brugge, Belgium, 8000
Cliniques Univ. Saint Luc
Brussels, Belgium, 1200
Grand Hopital de Charleroi
Charleroi, Belgium, 6000
UZ Antwerp
Edegem, Belgium, 2650
UZ Leuven
Leuven, Belgium, 3000
CHU UCL Namur
Namur, Belgium, 5000
Brazil
Hospital Bruno Born
Lajeado, Rio Grande Do Sul, Brazil, 95900-000
Irmandade da Santa Casa de
Porto Alegre, Rio Grande Do Sul, Brazil, 90020-090
Hosp Clinicas de Porto Alegre
Porto Alegre, Rio Grande Do Sul, Brazil, 90035-903
Canada, Ontario
Sunnybrook Health Sciences Ctr
Toronto, Ontario, Canada, M4N 3M5
Canada, Quebec
CHUM - Notre-Dame Hospital
Montreal, Quebec, Canada, H2L 4M1
Jewish General Hospital
Montreal, Quebec, Canada, H3T 1E2
CHUQ-Hospital St. Sacrement
Quebec City, Quebec, Canada, G1S 4L8
Czechia
Masarykuv onkologikcy ustav
Brno, Czechia, 656 53
Palacky University
Olomouc, Czechia, 779 00
Vseobecna Fakultni Nemocnice
Prague, Czechia, 128 08
Denmark
Rigshospitalet, Finsen Centre
Copenhagen, Denmark, 2100
Vejle Sygehus
Vejle, Denmark, 7100
Finland
Docrates Cancer Center
Helsinki, Finland, 00180
Tampere University Hospital
Tampere, Finland, 33521
France
Hopital Universitaire Purpan - Hopital Pierre-Paul Riquet
Toulouse, Haute-Garonne, France, 31059
Institut de Cancer de l'Ouest
St Herblain CEDEX, Loire-Atlantique, France, 44805
Pays-Basque Ctr Oncology/Radio
Bayonne, France, 64100
Centre Leon Berard
Lyon CEDEX 08, France, 69373
Institut Paoli-Calmettes
Marseille, France, 13273
Institut Curie
Paris, France, 75248
Hopital Rene Huguenin
Saint-cloud, France, 92210
Centre Paul Strauss
Strasbourg, France, 67065
Hungary
Bajcsy-Zsilinszky Korhaz
Budapest, Hungary, 1106
Debreceni Egyetem Klinikai Koz
Debrecen, Hungary, 4032
Jasz-Nagykun-Szolnok Megyei
Szolnok, Hungary, 5004
Israel
Soroka Medical Ctr
Be'er Sheva, Israel, 84101
Assaf Harofeh Medical Center
Be'er Ya'akov, Israel, 70300
Rambam Health Care Campus
Haifa, Israel, 3109601
Shaare Zedek Medical Center
Jerusalem, Israel, 91031
Hadassah University Hospital
Jerusalem, Israel, 91120
Rabin Medical Center
Petah Tikva, Israel, 49100
Sheba Medical Center
Ramat Gan, Israel, 5262100
Kaplan Medical Center
Rehovot, Israel, 76100
Netherlands
Erasmus Medisch Centrum
Rotterdam, Netherlands, 3015 CE
Norway
Haukeland University Hospital
Bergen, Norway, 5021
Poland
Centrum Onkologii Lukaszczyka
Bydgoszcz, Poland, 85-796
Olsztynski Osrodek Onkologi
Olsztyn, Poland, 10-513
NZOZ Centrum Medyczne HCP
Poznan, Poland, 61-485
Wielkopolskie Centrum Onkologi
Poznan, Poland, 61-866
Mrukmed. Lekarz Beata Madej
Rzeszow, Poland, 35-922
Romania
S.C. lanuli Med Consult SRL
Bucharest, Romania, 020962
lnstitutul Oncologic Trestiore
Bucharest, Romania, 022328
Spitalul Clinic Judetean de Ur
Cluj, Romania, 400006
Inst Oncology Prof. Chiricuta
Cluj, Romania, 400010
Sc Oncolab Srl
Craiova, Romania, 200385
Russian Federation
Chelyabinsk Reg Clin Oncology
Chelyabinsk, Russian Federation, 454087
NN Blokhin Russian Cancer
Moscow, Russian Federation, 115478
Murmansk Regional Onc Dispens
Murmansk, Russian Federation, 183047
City Clinical Hospital 1
Novosibirsk, Russian Federation, 630075
Pyatigorsk Oncology Dispensary
Pyatigorsk, Russian Federation, 357502
St. Petersburg Healthcare
St. Petersburg, Russian Federation, 197183
N.N. Petrov Research Inst Onc
St. Petersburg, Russian Federation, 197758
Volgograd Reg Onc Disp #3
Volzhsky, Russian Federation, 404130
Spain
Hosp Santa Creu i Sant Pau
Barcelona, Spain, 08026
Hospital Univ Vall d'Hebron
Barcelona, Spain, 08035
Hospital Genl Gregorio Maranon
Madrid, Spain, 28007
Hosp Univ Madrid Sanchinarro
Madrid, Spain, 28050
Hosp Uni Virgen de la Victoria
Malaga, Spain, 29010
Hosp Clin Univ de Valencia
Valencia, Spain, 46010
Sweden
Sahlgrenska University Hosp
Goteborg, Sweden, 413 45
Skanes Universitetssjukhus
Malmo, Sweden, 205 02
Karolinska Univ Sjukhuset
Solna, Sweden, 17176
Ukraine
Cherkassy Regional Onc Ctr
Cherkasy, Ukraine, 18000
City Multi-Field Clin Hosp #4
Dnipropetrovsk, Ukraine, 49102
Kharkiv Regional Clinical Onco
Kharkiv, Ukraine, 61070
Lviv State Onc Local Treatment
Lviv, Ukraine, 79031
Odessa National Medical Univ
Odesa, Ukraine, 65026
Poltava Regional Clinical Onco
Poltava, Ukraine, 36011
Sumy Reg Clinical Oncology Ctr
Sumy, Ukraine, 40005

Sponsors and Collaborators

AbbVie

Investigators

Study Director:	AbbVie Inc.	AbbVie

More Information

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Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Han HS, Diéras V, Robson M, Palácová M, Marcom PK, Jager A, Bondarenko I, Citrin D, Campone M, Telli ML, Domchek SM, Friedlander M, Kaufman B, Garber JE, Shparyk Y, Chmielowska E, Jakobsen EH, Kaklamani V, Gradishar W, Ratajczak CK, Nickner C, Qin Q, Qian J, Shepherd SP, Isakoff SJ, Puhalla S. Veliparib with temozolomide or carboplatin/paclitaxel versus placebo with carboplatin/paclitaxel in patients with BRCA1/2 locally recurrent/metastatic breast cancer: randomized phase II study. Ann Oncol. 2018 Jan 1;29(1):154-161. doi: 10.1093/annonc/mdx505.

Isakoff SJ, Puhalla S, Domchek SM, Friedlander M, Kaufman B, Robson M, Telli ML, Diéras V, Han HS, Garber JE, Johnson EF, Maag D, Qin Q, Giranda VL, Shepherd SP. A randomized Phase II study of veliparib with temozolomide or carboplatin/paclitaxel versus placebo with carboplatin/paclitaxel in BRCA1/2 metastatic breast cancer: design and rationale. Future Oncol. 2017 Feb;13(4):307-320. doi: 10.2217/fon-2016-0412. Epub 2016 Oct 14.

Responsible Party:	AbbVie
ClinicalTrials.gov Identifier:	NCT01506609 History of Changes
Other Study ID Numbers:	M12-895; 2011-002913-12 ( EudraCT Number )
First Posted:	January 10, 2012
Last Update Posted:	February 14, 2018
Last Verified:	February 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD:	Undecided

Studies a U.S. FDA-regulated Drug Product:		Yes
Studies a U.S. FDA-regulated Device Product:		No
Product Manufactured in and Exported from the U.S.:		No

Keywords provided by AbbVie:

PARP; TMZ; Temodal; Carboplatin; veliparib; BRCA2 mutation carrier; Breast cancer; Metastatic breast cancer	temozolomide; BRCA1 mutation carrier; ABT-888; Paclitaxel; Recurrent breast cancer; Temodar; Locally recurrent

Additional relevant MeSH terms:

Breast Neoplasms; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Paclitaxel; Temozolomide; Veliparib; Albumin-Bound Paclitaxel; Carboplatin; Dacarbazine	Antineoplastic Agents, Phytogenic; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents, Alkylating; Alkylating Agents; Poly(ADP-ribose) Polymerase Inhibitors; Enzyme Inhibitors