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

Metastatic Breast Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01506609
• Other study ID #: M12-895
• Secondary ID: 2011-002913-12
• Status: Completed
• Phase: Phase 2
• Start date: January 23, 2012
• Est. completion date: September 2, 2020

Study information

• Verified date: September 2021
• Source: AbbVie
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 294
• Est. completion date: September 2, 2020
• Est. primary completion date: December 13, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Breast Neoplasms
• Metastatic Breast Cancer

Intervention

Drug:
• Placebo

• Veliparib

• Carboplatin

• Temozolomide

• Paclitaxel

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
AbbVie

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Belgium,  Brazil,  Canada,  Czechia,  Denmark,  Finland,  France,  Hungary,  Israel,  Netherlands,  Norway,  Poland,  Romania,  Russian Federation,  Spain,  Sweden,  Ukraine, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Overall Survival (OS)	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.	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.
Secondary	Clinical Benefit Rate (CBR) at 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).	Week 18
Secondary	Objective Response Rate (ORR)	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.	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.
Secondary	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	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.	Baseline, Week 18