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

NCT01506609 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: M12-8952011-002913-12
• Study Type: interventional
• Target: 294
• Locations: 20 countries
• Sites: 120

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.

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

Outcome Measures

Primary Outcomes (1)

• Progression-Free Survival (PFS)

  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.

  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 (4)

• 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.

• Clinical Benefit Rate (CBR) at Week 18

  Week 18

• 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.

• 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

Study Arms (3)

Veliparib with Temozolomide

EXPERIMENTAL

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.

Drug: Veliparib; Drug: Temozolomide

Placebo with Carboplatin and Paclitaxel

PLACEBO COMPARATOR

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.

Drug: Placebo; Drug: Carboplatin; Drug: Paclitaxel

Veliparib with Carboplatin and Paclitaxel

EXPERIMENTAL

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.

Drug: Veliparib; Drug: Carboplatin; Drug: Paclitaxel

Interventions

Placebo DRUG

Placebo with Carboplatin and Paclitaxel

Veliparib DRUG

Also known as: ABT-888

Veliparib with Carboplatin and Paclitaxel; Veliparib with Temozolomide

Carboplatin DRUG

Placebo with Carboplatin and Paclitaxel; Veliparib with Carboplatin and Paclitaxel

Temozolomide DRUG

Also known as: Temodal

Veliparib with Temozolomide

Paclitaxel DRUG

Also known as: Taxol

Placebo with Carboplatin and Paclitaxel; Veliparib with Carboplatin and Paclitaxel

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• AbbVie: lead

Study Sites (120)

University of Alabama at Birmingham - Main /ID# 62994

Birmingham, Alabama, 35233, United States

Location

Banner MD Anderson Cancer Ctr /ID# 118695

Gilbert, Arizona, 85234, United States

Location

University of Arkansas for Medical Sciences /ID# 60750

Little Rock, Arkansas, 72205, United States

Location

Moore UC San Diego Cancer Center /ID# 60754

La Jolla, California, 92093, United States

Location

The Angeles Clinic and Researc /ID# 60743

Los Angeles, California, 90025, United States

Location

Stanford University School of Med /ID# 65488

Stanford, California, 94305-2200, United States

Location

Cedars-Sinai Medical Center - West Hollywood /ID# 60760

West Hollywood, California, 90048, United States

Location

Univ of Colorado Cancer Center /ID# 60751

Aurora, Colorado, 80045, United States

Location

Lynn Cancer Institute, Boca /ID# 60749

Boca Raton, Florida, 33486, United States

Location

Holy Cross Hospital /ID# 62995

Fort Lauderdale, Florida, 33308, United States

Location

Moffitt Cancer Center /ID# 60746

Tampa, Florida, 33612-9416, United States

Location

Florida Cancer Specialists - East /ID# 60762

West Palm Beach, Florida, 33401, United States

Location

University of Illinois - Chicago /ID# 106175

Chicago, Illinois, 60607, United States

Location

Northwestern University Feinberg School of Medicine /ID# 60755

Chicago, Illinois, 60611-2927, United States

Location

Rush University Medical Center /ID# 65489

Chicago, Illinois, 60612, United States

Location

Midwestern Regional CTC /ID# 60744

Zion, Illinois, 60099, United States

Location

Johns Hopkins University /ID# 60759

Baltimore, Maryland, 21287, United States

Location

Massachusetts General Hospital /ID# 64582

Boston, Massachusetts, 02114, United States

Location

Dana-Farber Cancer Institute /ID# 93833

Boston, Massachusetts, 02215, United States

Location

William Beaumont Hospital /ID# 95417

Royal Oak, Michigan, 48073-6710, United States

Location

Washington University-School of Medicine /ID# 62724

St Louis, Missouri, 63110, United States

Location

Beth Israel Medical Center /ID# 87993

New York, New York, 10003, United States

Location

Memorial Sloan Kettering Cancer Center-Koch Center /ID# 63222

New York, New York, 10065-6007, United States

Location

Duke University Medical Center /ID# 60747

Durham, North Carolina, 27710-3000, United States

Location

Penn State University and Milton S. Hershey Medical Center /ID# 62723

Hershey, Pennsylvania, 17033, United States

Location

University of Pennsylvania /ID# 60753

Philadelphia, Pennsylvania, 19104-5502, United States

Location

University of Pittsburgh MC /ID# 60758

Pittsburgh, Pennsylvania, 15260, United States

Location

University of Pittsburgh MC /ID# 65486

Pittsburgh, Pennsylvania, 15260, United States

Location

Medical University of South Carolina /ID# 60752

Charleston, South Carolina, 29425, United States

Location

The West Clinic /ID# 65487

Memphis, Tennessee, 38120, United States

Location

The West Clinic /ID# 94599

Memphis, Tennessee, 38120, United States

Location

The West Clinic /ID# 94600

Memphis, Tennessee, 38120, United States

Location

UT Southwestern Medical Center /ID# 60745

Dallas, Texas, 75390-7208, United States

Location

Houston Methodist Hospital - Scurlock Tower /ID# 60742

Houston, Texas, 77030, United States

Location

Coiba /Id# 65219

Berazategui, Buenos Aires, 1884, Argentina

Location

ISIS Centro Especializado /ID# 65226

Santa Fe, 3000, Argentina

Location

The Prince of Wales Hospital /ID# 63271

Randwick, New South Wales, 2031, Australia

Location

Southern Medical Day Care Ctr /ID# 63274

Wollongong, New South Wales, 2500, Australia

Location

Mater Misericordiae Limited /ID# 63276

South Brisbane, Queensland, 4101, Australia

Location

Royal Adelaide Hospital /ID# 63280

Adelaide, South Australia, 5000, Australia

Location

Royal Hobart Hospital /ID# 63279

Hobart, Tasmania, 7000, Australia

Location

Peter MacCallum Cancer Ctr /ID# 63272

Melbourne, Victoria, 3000, Australia

Location

Royal Melbourne Hospital /ID# 63278

Parkville, Victoria, 3050, Australia

Location

Mount Hospital /ID# 65262

Perth, Western Australia, 6000, Australia

Location

Cliniques Universitaires Saint Luc /ID# 96135

Woluwe-Saint-Lambert, Brussels Capital, 1200, Belgium

Location

Grand Hôpital de Charleroi /ID# 96136

Charleroi, Hainaut, 6000, Belgium

Location

AZ St-Jan Brugge-Oostende AV /ID# 107315

Bruges, West-Vlaanderen, 8000, Belgium

Location

UZ Antwerp /ID# 96945

Edegem, 2650, Belgium

Location

UZ Leuven /ID# 96138

Leuven, 3000, Belgium

Location

CHU UCL Namur /ID# 110595

Namur, 5000, Belgium

Location

Hospital Bruno Born / Sociedade Beneficencia e Caridade de Lajeado /ID# 65247

Lajeado, Rio Grande do Sul, 95900-000, Brazil

Location

Irmandade da Santa Casa de /ID# 65244

Porto Alegre, Rio Grande do Sul, 90020-090, Brazil

Location

Hospital de Clinicas de Porto Alegre /ID# 65242

Porto Alegre, Rio Grande do Sul, 90035-903, Brazil

Location

Sunnybrook Health Sciences Ctr /ID# 77373

Toronto, Ontario, M4N 3M5, Canada

Location

CHUM - Notre-Dame Hospital /ID# 67862

Montreal, Quebec, H2X 0A9, Canada

Location

Jewish General Hospital /ID# 69893

Montreal, Quebec, H3T 1E2, Canada

Location

CHUQ-Hospital St. Sacrement /ID# 68902

Québec, Quebec, G1S 4L8, Canada

Location

Masarykuv onkologicky ustav /ID# 65170

Brno, 656 53, Czechia

Location

Palacky University /ID# 63923

Olomouc, 779 00, Czechia

Location

Vseobecna Fakultni Nemocnice /ID# 65172

Prague, 128 08, Czechia

Location

Vejle Sygehus /ID# 65173

Vejle, Region Syddanmark, 7100, Denmark

Location

Rigshospitalet, Finsen Centre /ID# 67822

Copenhagen, 2100, Denmark

Location

Docrates Cancer Center /ID# 63924

Helsinki, 00180, Finland

Location

Tampere University Hospital /ID# 102417

Tampere, 33521, Finland

Location

Hopital Universitaire Purpan /ID# 98815

Toulouse, Haute-Garonne, 31059, France

Location

Institut de Cancer de l'Ouest /ID# 63927

Saint-Herblain, Loire-Atlantique, 44805, France

Location

Centre Leon Berard /ID# 106675

Lyon, Rhone, 69373, France

Location

Pays-Basque Ctr Oncology/Radio /ID# 65176

Bayonne, 64100, France

Location

Institut Paoli-Calmettes /ID# 65175

Marseille, 13273, France

Location

Hopital Rene Huguenin /ID# 65177

Saint-Cloud, 92210, France

Location

Centre Paul Strauss /ID# 100275

Strasbourg, 67065, France

Location

Institut Curie /ID# 63926

Paris, Île-de-France Region, 75248, France

Location

Bajcsy-Zsilinszky Korhaz /ID# 65179

Budapest, 1106, Hungary

Location

Debreceni Egyetem Klinikai Kozpont /ID# 65178

Debrecen, 4032, Hungary

Location

Jasz-Nagykun-Szolnok Megyei Hetenyi Geza Korhaz /ID# 63928

Szolnok, 5004, Hungary

Location

Rabin Medical Center /ID# 63929

Petakh Tikva, Tel Aviv, 4941492, Israel

Location

Soroka University Medical Center /ID# 65180

Beersheba, 84101, Israel

Location

Assaf Harofeh Medical Center /ID# 65181

Be’er Ya‘aqov, 70300, Israel

Location

Rambam Health Care Campus /ID# 63930

Haifa, 3109601, Israel

Location

Shaare Zedek Medical Center /ID# 116575

Jerusalem, 91031, Israel

Location

Gastroenterology Institute, Division of Medicine /ID# 63931

Jerusalem, 91120, Israel

Location

Sheba Medical Center /ID# 63932

Ramat Gan, 5239424, Israel

Location

Kaplan Medical Center /ID# 63933

Rehovot, 76100, Israel

Location

Erasmus Medisch Centrum /ID# 96275

Rotterdam, 3015 CE, Netherlands

Location

Haukeland University Hospital /ID# 67982

Bergen, Hordaland, 5021, Norway

Location

Mrukmed. Lekarz Beata Madej Mruk i Partner /ID# 94975

Rzeszów, Podkarpackie Voivodeship, 35-021, Poland

Location

Centrum Onkologii Lukaszczyka /ID# 73393

Bydgoszcz, 85-796, Poland

Location

Olsztynski Osrodek Onkologi /ID# 71060

Olsztyn, 10-513, Poland

Location

NZOZ Centrum Medyczne HCP /ID# 68102

Poznan, 61-485, Poland

Location

Wielkopolskie Centrum Onkologi /ID# 71061

Poznan, 61-866, Poland

Location

S.C. lanuli Med Consult SRL /ID# 106955

Bucharest, 020962, Romania

Location

lnstitutul Oncologic Trestiore /ID# 96742

Bucharest, 022328, Romania

Location

Spitalul Clinic Judetean de Urgenta /ID# 96741

Cluj-Napoca, 400006, Romania

Location

Inst Oncology Prof. Chiricuta /ID# 96740

Cluj-Napoca, 400010, Romania

Location

Sc Oncolab Srl /Id# 96745

Craiova, 200385, Romania

Location

Federal State Budgetary Scientific Institution N.N. Blokhin Russian Cancer Resea /ID# 65263

Moscow, Moscow, 115478, Russia

Location

Chelyabinsk Reg Clin Oncology /ID# 63938

Chelyabinsk, 454087, Russia

Location

State Regional Budgetary Healthcare Institution " Murmansk Regional Oncology Dis /ID# 102415

Murmansk, 183047, Russia

Location

City Clinical Hospital 1 /ID# 102416

Novosibirsk, 630075, Russia

Location

Pyatigorsk Oncology Dispensary /ID# 65264

Pyatigorsk, 357502, Russia

Location

Birch A Healthcare /ID# 65265

Saint Petersburg, 197183, Russia

Location

N.N. Petrov Research Inst Onc /ID# 65269

Saint Petersburg, 197758, Russia

Location

N.N. Petrov Research Inst Onc /ID# 78973

Saint Petersburg, 197758, Russia

Location

Volgograd Reg Onc Disp #3 /ID# 98035

Volzhsky, 404130, Russia

Location

Hospital Universitario Vall d'Hebron /ID# 97415

Barcelona, 08035, Spain

Location

Hospital Santa Creu i Sant Pau /ID# 97418

Barcelona, 08041, Spain

Location

Hospital General Universitario Gregorio Maranon /ID# 97417

Madrid, 28007, Spain

Location

Hospital Universitario HM Sanchinarro /ID# 97416

Madrid, 28050, Spain

Location

Hospital Universitario Virgen de la Victoria /ID# 97976

Málaga, 29010, Spain

Location

Hospital Clinico Universitario de Valencia /ID# 97975

Valencia, 46010, Spain

Location

Skanes Universitetssjukhus /ID# 96475

Malmo, Skåne County, 214 28, Sweden

Location

Sahlgrenska University Hosp /ID# 97715

Gothenburg, 413 45, Sweden

Location

Karolinska Univ Sjukhuset /ID# 98037

Solna, 17176, Sweden

Location

Cherkassy Regional Onc Ctr /ID# 97698

Cherkasy, 18000, Ukraine

Location

Municipal Non-Profit Enterprise City Clinical Hospital No.4 of Dnipro City Counc /ID# 63940

Dnipro, 49102, Ukraine

Location

Communal non-profit enterprise Regional Center of Oncology /ID# 97696

Kharkiv, 61070, Ukraine

Location

Lviv Oncological Regional Therapeutical and Diagnostic Centre /ID# 63941

Lviv, 79031, Ukraine

Location

Odessa National Medical Univ /ID# 65278

Odesa, 65026, Ukraine

Location

Poltava Regional Clinical Oncology Centre of Poltava Regional Council /ID# 97697

Poltava, 36011, Ukraine

Location

Municipal Non-Profit Enterprise of Sumy Regional Council Sumy Regional Clinical /ID# 65280

Sumy, 40022, Ukraine

Location

Related Publications (2)

• 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.

  PMID: 29045554 BACKGROUND

• 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.

  PMID: 27739325 DERIVED

MeSH Terms

Conditions

Breast Neoplasms

Interventions

veliparib; Carboplatin; Temozolomide; Paclitaxel

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Dacarbazine; Triazenes; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes

Results Point of Contact

• Title: Global Medical Services
• Organization: AbbVie

abbvieclinicaltrials@abbvie.com

800-633-9110

Study Officials

• AbbVie Inc.

  AbbVie

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR
• Expanded Access: Yes

Study Record Dates

• First Submitted: January 6, 2012
• First Posted: January 10, 2012
• Study Start: January 23, 2012
• Primary Completion: December 13, 2018
• Study Completion: September 2, 2020
• Last Updated: October 25, 2021
• Results First Posted: October 25, 2021

Record last verified: 2021-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• Time Frame: Data requests can be submitted at any time and the data will be accessible for 12 months, with possible extensions considered.
• Access Criteria: Access to this clinical trial data can be requested by any qualified researchers who engage in rigorous, independent scientific research, and will be provided following review and approval of a research proposal and Statistical Analysis Plan (SAP) and execution of a Data Sharing Agreement (DSA). For more information on the process, or to submit a request, visit the following link.

Locations

BE (6); CA (4); DK (2); UA (7); AR (2); BR (3); ES (6); US (34); HU (3); IL (8); FI (2); NL (1); RO (5); SE (3); AU (8); FR (8); NO (1); CZ (3); PL (5); RU (9)