Clinical trial NCT01506609: 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
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Metastatic Breast Cancer
Keywords: 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
Lead sponsor: AbbVie
Sponsor class: INDUSTRY
First posted: 2012-01-10
Enrollment: 294
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility 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, active infection, myocardial infarction, stroke, or transient ischemic attack, psychiatric illness/social situations that would limit compliance.
* Pregnant or breastfeeding.

Primary outcomes:
measure: Progression-Free Survival (PFS)
timeFrame: 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.
Secondary outcomes:
measure: Overall Survival (OS)
timeFrame: 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.
measure: Clinical Benefit Rate (CBR) at Week 18
timeFrame: Week 18
measure: Objective Response Rate (ORR)
timeFrame: 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.
measure: 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
timeFrame: Baseline, Week 18
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham - Main /ID# 62994
state: Alabama
city: Gilbert
country: United States
facility: Banner MD Anderson Cancer Ctr /ID# 118695
state: Arizona
city: Little Rock
country: United States
facility: University of Arkansas for Medical Sciences /ID# 60750
state: Arkansas
city: La Jolla
country: United States
facility: Moore UC San Diego Cancer Center /ID# 60754
state: California
city: Los Angeles
country: United States
facility: The Angeles Clinic and Researc /ID# 60743
state: California
city: Stanford
country: United States
facility: Stanford University School of Med /ID# 65488
state: California
city: West Hollywood
country: United States
facility: Cedars-Sinai Medical Center - West Hollywood /ID# 60760
state: California
city: Aurora
country: United States
facility: Univ of Colorado Cancer Center /ID# 60751
state: Colorado
city: Boca Raton
country: United States
facility: Lynn Cancer Institute, Boca /ID# 60749
state: Florida
city: Fort Lauderdale
country: United States
facility: Holy Cross Hospital /ID# 62995
state: Florida
city: Tampa
country: United States
facility: Moffitt Cancer Center /ID# 60746
state: Florida
city: West Palm Beach
country: United States
facility: Florida Cancer Specialists - East /ID# 60762
state: Florida
city: Chicago
country: United States
facility: University of Illinois - Chicago /ID# 106175
state: Illinois
city: Chicago
country: United States
facility: Northwestern University Feinberg School of Medicine /ID# 60755
state: Illinois
city: Chicago
country: United States
facility: Rush University Medical Center /ID# 65489
state: Illinois
city: Zion
country: United States
facility: Midwestern Regional CTC /ID# 60744
state: Illinois
city: Baltimore
country: United States
facility: Johns Hopkins University /ID# 60759
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital /ID# 64582
state: Massachusetts
city: Boston
country: United States
facility: Dana-Farber Cancer Institute /ID# 93833
state: Massachusetts
city: Royal Oak
country: United States
facility: William Beaumont Hospital /ID# 95417
state: Michigan
city: Saint Louis
country: United States
facility: Washington University-School of Medicine /ID# 62724
state: Missouri
city: New York
country: United States
facility: Beth Israel Medical Center /ID# 87993
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center-Koch Center /ID# 63222
state: New York
city: Durham
country: United States
facility: Duke University Medical Center /ID# 60747
state: North Carolina
city: Hershey
country: United States
facility: Penn State University and Milton S. Hershey Medical Center /ID# 62723
state: Pennsylvania
city: Philadelphia
country: United States
facility: University of Pennsylvania /ID# 60753
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh MC /ID# 60758
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh MC /ID# 65486
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina /ID# 60752
state: South Carolina
city: Memphis
country: United States
facility: The West Clinic /ID# 65487
state: Tennessee
city: Memphis
country: United States
facility: The West Clinic /ID# 94599
state: Tennessee
city: Memphis
country: United States
facility: The West Clinic /ID# 94600
state: Tennessee
city: Dallas
country: United States
facility: UT Southwestern Medical Center /ID# 60745
state: Texas
city: Houston
country: United States
facility: Houston Methodist Hospital - Scurlock Tower /ID# 60742
state: Texas
city: Berazategui, Buenos Aires
country: Argentina
facility: Coiba /Id# 65219
city: Santa Fe
country: Argentina
facility: ISIS Centro Especializado /ID# 65226
city: Randwick
country: Australia
facility: The Prince of Wales Hospital /ID# 63271
state: New South Wales
city: Wollongong
country: Australia
facility: Southern Medical Day Care Ctr /ID# 63274
state: New South Wales
city: South Brisbane
country: Australia
facility: Mater Misericordiae Limited /ID# 63276
state: Queensland
city: Adelaide
country: Australia
facility: Royal Adelaide Hospital /ID# 63280
state: South Australia
city: Hobart
country: Australia
facility: Royal Hobart Hospital /ID# 63279
state: Tasmania
city: Melbourne
country: Australia
facility: Peter MacCallum Cancer Ctr /ID# 63272
state: Victoria
city: Parkville
country: Australia
facility: Royal Melbourne Hospital /ID# 63278
state: Victoria
city: Perth
country: Australia
facility: Mount Hospital /ID# 65262
state: Western Australia
city: Woluwe-Saint-Lambert
country: Belgium
facility: Cliniques Universitaires Saint Luc /ID# 96135
state: Bruxelles-Capitale
city: Charleroi
country: Belgium
facility: Grand Hôpital de Charleroi /ID# 96136
state: Hainaut
city: Brugge
country: Belgium
facility: AZ St-Jan Brugge-Oostende AV /ID# 107315
state: West-Vlaanderen
city: Edegem
country: Belgium
facility: UZ Antwerp /ID# 96945
city: Leuven
country: Belgium
facility: UZ Leuven /ID# 96138
city: Namur
country: Belgium
facility: CHU UCL Namur /ID# 110595
city: Lajeado
country: Brazil
facility: Hospital Bruno Born / Sociedade Beneficencia e Caridade de Lajeado /ID# 65247
state: Rio Grande Do Sul
city: Porto Alegre
country: Brazil
facility: Irmandade da Santa Casa de /ID# 65244
state: Rio Grande Do Sul
city: Porto Alegre
country: Brazil
facility: Hospital de Clinicas de Porto Alegre /ID# 65242
state: Rio Grande Do Sul
city: Toronto
country: Canada
facility: Sunnybrook Health Sciences Ctr /ID# 77373
state: Ontario
city: Montreal
country: Canada
facility: Jewish General Hospital /ID# 69893
state: Quebec
city: Montréal
country: Canada
facility: CHUM - Notre-Dame Hospital /ID# 67862
state: Quebec
city: Quebec City
country: Canada
facility: CHUQ-Hospital St. Sacrement /ID# 68902
state: Quebec
city: Brno
country: Czechia
facility: Masarykuv onkologicky ustav /ID# 65170
city: Olomouc
country: Czechia
facility: Palacky University /ID# 63923
city: Prague
country: Czechia
facility: Vseobecna Fakultni Nemocnice /ID# 65172
city: Vejle
country: Denmark
facility: Vejle Sygehus /ID# 65173
state: Syddanmark
city: Copenhagen
country: Denmark
facility: Rigshospitalet, Finsen Centre /ID# 67822
city: Helsinki
country: Finland
facility: Docrates Cancer Center /ID# 63924
city: Tampere
country: Finland
facility: Tampere University Hospital /ID# 102417
city: Toulouse
country: France
facility: Hopital Universitaire Purpan /ID# 98815
state: Haute-Garonne
city: Paris CEDEX 05
country: France
facility: Institut Curie /ID# 63926
state: Ile-de-France
city: St Herblain CEDEX
country: France
facility: Institut de Cancer de l'Ouest /ID# 63927
state: Loire-Atlantique
city: Lyon CEDEX 08
country: France
facility: Centre Leon Berard /ID# 106675
state: Rhone
city: Bayonne
country: France
facility: Pays-Basque Ctr Oncology/Radio /ID# 65176
city: Marseille
country: France
facility: Institut Paoli-Calmettes /ID# 65175
city: Saint-cloud
country: France
facility: Hopital Rene Huguenin /ID# 65177
city: Strasbourg
country: France
facility: Centre Paul Strauss /ID# 100275
city: Budapest
country: Hungary
facility: Bajcsy-Zsilinszky Korhaz /ID# 65179
city: Debrecen
country: Hungary
facility: Debreceni Egyetem Klinikai Kozpont /ID# 65178
city: Szolnok
country: Hungary
facility: Jasz-Nagykun-Szolnok Megyei Hetenyi Geza Korhaz /ID# 63928
city: Petakh Tikva
country: Israel
facility: Rabin Medical Center /ID# 63929
state: Tel-Aviv
city: Be'er Sheva
country: Israel
facility: Soroka University Medical Center /ID# 65180
city: Be'er Ya'akov
country: Israel
facility: Assaf Harofeh Medical Center /ID# 65181
city: Haifa
country: Israel
facility: Rambam Health Care Campus /ID# 63930
city: Jerusalem
country: Israel
facility: Shaare Zedek Medical Center /ID# 116575
city: Jerusalem
country: Israel
facility: Gastroenterology Institute, Division of Medicine /ID# 63931
city: Ramat Gan
country: Israel
facility: Sheba Medical Center /ID# 63932
city: Rehovot
country: Israel
facility: Kaplan Medical Center /ID# 63933
city: Rotterdam
country: Netherlands
facility: Erasmus Medisch Centrum /ID# 96275
city: Bergen
country: Norway
facility: Haukeland University Hospital /ID# 67982
state: Hordaland
city: Rzeszów
country: Poland
facility: Mrukmed. Lekarz Beata Madej Mruk i Partner /ID# 94975
state: Podkarpackie
city: Bydgoszcz
country: Poland
facility: Centrum Onkologii Lukaszczyka /ID# 73393
city: Olsztyn
country: Poland
facility: Olsztynski Osrodek Onkologi /ID# 71060
city: Poznan
country: Poland
facility: NZOZ Centrum Medyczne HCP /ID# 68102
city: Poznan
country: Poland
facility: Wielkopolskie Centrum Onkologi /ID# 71061
city: Bucharest
country: Romania
facility: S.C. lanuli Med Consult SRL /ID# 106955
city: Bucharest
country: Romania
facility: lnstitutul Oncologic Trestiore /ID# 96742
city: Cluj
country: Romania
facility: Spitalul Clinic Judetean de Urgenta /ID# 96741
city: Cluj
country: Romania
facility: Inst Oncology Prof. Chiricuta /ID# 96740
city: Craiova
country: Romania
facility: Sc Oncolab Srl /Id# 96745
city: Moscow
country: Russian Federation
facility: Federal State Budgetary Scientific Institution N.N. Blokhin Russian Cancer Resea /ID# 65263
state: Moskva
city: Chelyabinsk
country: Russian Federation
facility: Chelyabinsk Reg Clin Oncology /ID# 63938
city: Murmansk
country: Russian Federation
facility: State Regional Budgetary Healthcare Institution " Murmansk Regional Oncology Dis /ID# 102415
city: Novosibirsk
country: Russian Federation
facility: City Clinical Hospital 1 /ID# 102416
city: Pyatigorsk
country: Russian Federation
facility: Pyatigorsk Oncology Dispensary /ID# 65264
city: St. Petersburg
country: Russian Federation
facility: Birch A Healthcare /ID# 65265
city: St. Petersburg
country: Russian Federation
facility: N.N. Petrov Research Inst Onc /ID# 65269
city: St. Petersburg
country: Russian Federation
facility: N.N. Petrov Research Inst Onc /ID# 78973
city: Volzhsky
country: Russian Federation
facility: Volgograd Reg Onc Disp #3 /ID# 98035
city: Barcelona
country: Spain
facility: Hospital Universitario Vall d'Hebron /ID# 97415
city: Barcelona
country: Spain
facility: Hospital Santa Creu i Sant Pau /ID# 97418
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Maranon /ID# 97417
city: Madrid
country: Spain
facility: Hospital Universitario HM Sanchinarro /ID# 97416
city: Malaga
country: Spain
facility: Hospital Universitario Virgen de la Victoria /ID# 97976
city: Valencia
country: Spain
facility: Hospital Clinico Universitario de Valencia /ID# 97975
city: Malmö
country: Sweden
facility: Skanes Universitetssjukhus /ID# 96475
state: Skane Lan
city: Goteborg
country: Sweden
facility: Sahlgrenska University Hosp /ID# 97715
city: Solna
country: Sweden
facility: Karolinska Univ Sjukhuset /ID# 98037
city: Cherkasy
country: Ukraine
facility: Cherkassy Regional Onc Ctr /ID# 97698
city: Dnipro
country: Ukraine
facility: Municipal Non-Profit Enterprise City Clinical Hospital No.4 of Dnipro City Counc /ID# 63940
city: Kharkiv
country: Ukraine
facility: Communal non-profit enterprise Regional Center of Oncology /ID# 97696
city: Lviv
country: Ukraine
facility: Lviv Oncological Regional Therapeutical and Diagnostic Centre /ID# 63941
city: Odesa
country: Ukraine
facility: Odessa National Medical Univ /ID# 65278
city: Poltava
country: Ukraine
facility: Poltava Regional Clinical Oncology Centre of Poltava Regional Council /ID# 97697
city: Sumy
country: Ukraine
facility: Municipal Non-Profit Enterprise of Sumy Regional Council Sumy Regional Clinical /ID# 65280
Study officials:
affiliation: AbbVie
name: AbbVie Inc.
role: STUDY_DIRECTOR
References:
citation: Han HS, Dieras V, Robson M, Palacova 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.
citation: Isakoff SJ, Puhalla S, Domchek SM, Friedlander M, Kaufman B, Robson M, Telli ML, Dieras 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.