Study Comparing Veliparib Plus Carboplatin and Paclitaxel Versus Investigator's Choice of Standard Chemotherapy in Adults Receiving First Cytotoxic Chemotherapy for Metastatic or Advanced Non-Squamous Non-Small Cell Lung Cancer (NSCLC) and Who Are Current or Former Smokers

Non-squamous Non-small Cell Lung Cancer Clinical Trial

Official title:

A Randomized, Open-Label, Multicenter, Phase 3 Trial Comparing Veliparib Plus Carboplatin and Paclitaxel Versus Investigator's Choice of Standard Chemotherapy in Subjects Receiving First Cytotoxic Chemotherapy for Metastatic or Advanced Non-Squamous Non-Small Cell Lung Cancer (NSCLC) and Who Are Current or Former Smokers

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02264990
• Other study ID #: M14-359
• Secondary ID: 2014-002565-30
• Status: Completed
• Phase: Phase 3
• Start date: September 30, 2014
• Est. completion date: February 21, 2020

Study information

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

Clinical Trial Summary

The purpose of this study is to evaluate the safety and efficacy of veliparib plus carboplatin and paclitaxel versus the Investigator's choice of standard chemotherapy in adults with metastatic or advanced non-squamous non-small cell lung cancer.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 595
• Est. completion date: February 21, 2020
• Est. primary completion date: November 14, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Subject must be = 18 years of age with life expectancy > 12 weeks.
• Subject must have cytologically or histologically confirmed advanced or metastatic non-squamous NSCLC and are current or former smokers.
• Subject must have NSCLC that is not amenable to surgical resection or radiation with curative intent at time of screening.
• Subject must have at least 1 unidimensional measurable NSCLC lesion on a computed tomography (CT) scan as defined by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.

Exclusion Criteria:

• Subject has a known hypersensitivity to paclitaxel or to other drugs formulated with polyethoxylated castor oil (Cremophor).
• Subject has a known hypersensitivity to platinum compounds.
• Subject has peripheral neuropathy = grade 2.
• Subject has squamous NSCLC, or an untreated known epidermal growth factor receptor (EGFR) mutation of exon 19 deletion or L858R mutation in exon 21, or a known anaplastic lymphoma kinase (ALK) gene rearrangement.
• Subject has received prior cytotoxic chemotherapy or chemoradiotherapy for NSCLC.

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Non-squamous Non-small Cell Lung Cancer

Intervention

Drug:
• Paclitaxel
Administered by Intravenous infusion on Day 1 of each 21-day cycle
• Carboplatin
Administered by Intravenous infusion on Day 1 of each 21-day cycle
• Cisplatin
Administered by Intravenous infusion on Day 1 of each 21-day cycle
• Veliparib
Oral capsule, administered twice daily for 7 days in each 21-day cycle
• Pemetrexed
Administered by Intravenous infusion on Day 1 of each 21-day cycle

Locations

Country	Name	City	State
Argentina	Coiba /Id# 132153	Berazategui, Buenos Aires
Argentina	Centro Investigacion Pergamino /ID# 132152	Pergamino
Argentina	Hospital Britanico /ID# 134874	Rosario, Santa FE
Argentina	Instituto de Oncologia de Rosa /ID# 132150	Rosario, Santa FE
Australia	Flinders Centre for Innovation /ID# 134288	Bedford Park	South Australia
Australia	Royal Hobart Hospital /ID# 132477	Hobart	Tasmania
Australia	St George Hospital /ID# 132481	Kogarah	New South Wales
Australia	Southern Medical Day Care Ctr /ID# 132482	Wollongong	New South Wales
Canada	Qe Ii Hsc /Id# 133408	Halifax	Nova Scotia
Canada	Victoria Hospital /ID# 132161	London	Ontario
Canada	CSSS Alphonse-Desjardins, CHAU de Levis /ID# 132155	Quebec City	Quebec
Canada	Windsor Regional Hospital /ID# 135989	Windsor	Ontario
Czechia	Krajska nemocnice Liberec a.s. /ID# 132694	Liberec
Czechia	Univ Hosp Ostrava-Poruba /ID# 132690	Ostrava
Czechia	Multiscan s.r.o. /ID# 132689	Pardubice
Czechia	Vseobecna Fakultni Nemocnice /ID# 135118	Prague
Denmark	Odense Universitets Hospital /ID# 131912	Odense C	Syddanmark
Finland	Satakunnan Sairaanhoitopiiri /ID# 133632	Pori
Finland	Vaasa Central Hospital /ID# 131930	Vaasa
Germany	Charite-Univ. Berlin, Benjamin-Franklin /ID# 131927	Berlin
Germany	Lungen Clinic Grosshansdorf /ID# 131928	Grosshansdorf
Germany	Univ Klinik Eppendorf Hamburg /ID# 131926	Hamburg
Germany	Klinik Loewenstein GmbH /ID# 131925	Löwenstein
Hungary	Orszagos Koranyi Pulmonologiai Intezet /ID# 132738	Budapest XII	Budapest
Hungary	Debreceni Egyetem Klinikai Kozpont /ID# 132742	Debrecen
Hungary	Koch Robert Hospital /ID# 133440	Edelény
Hungary	Veszprem Megyei Tudogyogyintez /ID# 132739	Farkasgyepu
Hungary	Petz Aladar Megyei Oktato Korh /ID# 132741	Gyor
Hungary	Matrahaza Gyogyintezet /ID# 132743	Kékesteto
Hungary	CRU Hungary Egeszsegugyi és Szolgaltato Kft. /ID# 133441	Miskolc	Borsod-Abauj-Zemplen
Israel	Assaf Harofeh Medical Center /ID# 132830	Be'er Ya'akov
Israel	Shaare Zedek Medical Center /ID# 132834	Jerusalem
Israel	Meir Medical Center /ID# 132832	Kfar Saba
Israel	Sheba Medical Center /ID# 132833	Ramat Gan
Japan	National Cancer Center Hospital /ID# 135129	Chuo-ku	Tokyo
Japan	Hiroshima Citizens Hospital /ID# 135130	Hiroshima
Japan	Kishiwada City Hospital /ID# 136548	Kishiwada
Japan	The Cancer Institute Hospital Of JFCR /ID# 135492	Koto-ku	Tokyo
Japan	Kurume University Hospital /ID# 134117	Kurume-shi	Fukuoka
Japan	Aichi Cancer Center Hospital /ID# 134129	Nagoya-shi	Aichi
Japan	Kindai University Hospital /ID# 134112	Osaka-sayama-shi	Osaka
Japan	Osaka City General Hospital /ID# 134115	Osaka-shi	Osaka
Japan	Hokkaido University Hospital /ID# 134123	Sapporo-shi	Hokkaido
Japan	Sendai Kousei Hospital /ID# 135491	Sendai-shi	Miyagi
Japan	Yamaguchi - Ube Medical Center /ID# 135284	Ube-shi	Yamaguchi
Japan	Kanagawa Cardiovascular and Respiratory Center /ID# 134127	Yokohama-shi	Kanagawa
Korea, Republic of	Dong-A University Hospital /ID# 131609	Busan	Busan Gwang Yeogsi
Korea, Republic of	Chungbuk National Univ Hosp /ID# 131611	Cheongju
Korea, Republic of	Chonnam National University Hospital /ID# 131612	Gwangju	Jeonranamdo
Korea, Republic of	Inha University Hospital /ID# 147924	Jung-gu	Incheon Gwang Yeogsi
Korea, Republic of	Seoul National Univ Bundang ho /ID# 131610	Seongnam	Gyeonggido
Korea, Republic of	Samsung Medical Center /ID# 132471	Seoul	Seoul Teugbyeolsi
Netherlands	Vrije Universiteit Medisch Centrum /ID# 131967	Amsterdam
Netherlands	Catharina Ziekenhuis /ID# 131966	Eindhoven
Netherlands	Ziekenhuis St. Jansdal /ID# 131965	Harderwijk
Netherlands	St. Antonius Ziekenhuis /ID# 133635	Nieuwegein
Netherlands	Jeroen Bosch Ziekenhuis /ID# 131968	S Hertogenbosch
New Zealand	Canterbury District Health Boa /ID# 132469	Christchurch
New Zealand	Wellington Hospital (Capital and Coast District Health Board) /ID# 132470	Wellington
Russian Federation	archangel Clinical Oncology /ID# 132376	Arkhangelsk
Russian Federation	Moscow Regional Onc Dispensary /ID# 132381	Balashikha
Russian Federation	Belgorod Oncology Dispensary /ID# 142638	Belgorod
Russian Federation	Sverdlovsk Regional Oncology Center Dispensary /ID# 132375	Ekaterinburg	Sverdlovskaya Oblast
Russian Federation	Federal State Budgetary Scientific Institution N.N. Blokhin Russian Cancer Resea /ID# 137085	Moscow	Moskva
Russian Federation	Moscow Res Onc Inst Hertsen /ID# 132370	Moscow
Russian Federation	State Regional Budgetary Healthcare Institution " Murmansk Regional Oncology Dis /ID# 137087	Murmansk
Russian Federation	Orenburg Regional Clinical Onc /ID# 132371	Orenburg
Russian Federation	Strategic medical systems LLC /ID# 206383	Sankt-Peterburg
Russian Federation	Ogarev Mordovia State Univ /ID# 132377	Saransk
Russian Federation	LLC BioEq Ltd. /ID# 132372	St. Petersburg
Russian Federation	N.N. Petrov Research Inst Onc /ID# 137084	St. Petersburg
South Africa	Cape Town Oncology Trials /ID# 132734	Cape Town	Western Cape
South Africa	GVI Rondebosch Oncology Centre /ID# 132732	Cape Town	Western Cape
South Africa	Netcare Oncology Intervent Ctr /ID# 131777	Cape Town	Western Cape
South Africa	The Oncology Centre /ID# 131773	Durban	Kwazulu-Natal
South Africa	Sandton Oncology Medical Group /ID# 131774	Johannesburg
South Africa	GVI Oncology /ID# 133268	Port Elizabeth	Eastern Cape
South Africa	Dr Albert, Bouwer and Jordaan Incorporated /ID# 131775	Pretoria	Gauteng
South Africa	Mary Potter Oncology Centre /ID# 131776	Pretoria	Gauteng
Spain	Hospital Universitario Fundacion Alcorcon /ID# 132909	Alcorcon
Spain	Hospital General Universitario Alicante /ID# 132881	Alicante
Spain	Hospital Universitario Dexeus - Grupo Quironsalud /ID# 132876	Barcelona
Spain	Hospital Universitario Vall d'Hebron /ID# 132871	Barcelona
Spain	Hospital Duran i Reynals /ID# 132879	L'Hospitalet de Llobregat	Barcelona
Spain	Hospital Universitario HM Sanchinarro /ID# 132869	Madrid
Spain	Hospital Universitario La Paz /ID# 132870	Madrid
Spain	MD Anderson Madrid /ID# 132905	Madrid
Spain	Hospital Clinico Universitario de Valencia /ID# 132873	Valencia
Taiwan	Dalin Tzu Chi General Hospital /ID# 131872	Dalin Township
Taiwan	China Medical University Hosp /ID# 131870	Taichung City	Taichung
Taiwan	Taipei Medical University Hospital /ID# 133817	Taipei City
Taiwan	Taipei Veterans General Hosp /ID# 131871	Taipei City
Turkey	Ankara Univ Medical Faculty /ID# 131914	Ankara
Turkey	Hacettepe University Medical Faculty /ID# 131913	Ankara
Turkey	Uludag University Medical Faculty /ID# 131915	Bursa
Turkey	Dicle Universitesi Tip /ID# 136570	Diyarbakir
Turkey	Gaziantep Universitesi Med /ID# 131917	Gaziantep
Turkey	Dr. Suat Seren Gogus Has /ID# 136568	Izmir
Turkey	Inonu University /ID# 136569	Malatya
United Kingdom	Royal United Hospitals Bath /ID# 132851	Bath
United Kingdom	Belfast City Hospital /ID# 132858	Belfast
United Kingdom	Heart of England NHS Foundation Trust /ID# 132855	Birmingham
United Kingdom	Royal Blackburn Hospital /ID# 132853	Blackburn
United Kingdom	Cheltenham General Hospital /ID# 131951	Cheltenham	Gloucestershire
United Kingdom	Colchester General Hospital /ID# 133929	Colchester
United Kingdom	Castle Hill Hospital /ID# 135489	Cottingham
United Kingdom	Scunthorpe General Hospital /ID# 133931	Doncaster
United Kingdom	James Paget University Hosp /ID# 131954	Great Yarmouth
United Kingdom	Royal Gwent Hospital /ID# 133935	Gwent
United Kingdom	Huddersfield Royal Infirmary /ID# 132854	Huddersfield
United Kingdom	Leicester Royal Infirmary /ID# 133930	Leicester	England
United Kingdom	Charing Cross Hospital /ID# 131959	London
United Kingdom	The Newcastle Upon Tyne Hospitals NHS Foundation Trust Freeman Hospital /ID# 131661	Newcastle Upon Tyne
United Kingdom	Norfolk and Norwich Univ Hosp /ID# 131953	Norwich	Norfolk
United Kingdom	York Hospital /ID# 132859	York
United States	CBCC Global Research, Inc. at /ID# 132709	Bakersfield	California
United States	MD Anderson Cancer Center at Cooper - Camden /ID# 131490	Camden	New Jersey
United States	Gabrail Cancer Center Research /ID# 130205	Canton	Ohio
United States	UT Southwestern Medical Center /ID# 130236	Dallas	Texas
United States	Henry Ford Health System /ID# 130234	Detroit	Michigan
United States	California Cancer Assoc. R&E /ID# 131392	Encinitas	California
United States	California Cancer Assoc. R&E /ID# 131949	Encinitas	California
United States	NorthShore University HealthSystem - Evanston Hospital /ID# 130200	Evanston	Illinois
United States	University of Florida - Archer /ID# 132408	Gainesville	Florida
United States	The Jones Clinic, PC /ID# 130215	Germantown	Tennessee
United States	Goshen Center for Cancer Care /ID# 130216	Goshen	Indiana
United States	Clearview Cancer Institute /ID# 131434	Huntsville	Alabama
United States	Cancer Center of Acadiana /ID# 133611	Lafayette	Louisiana
United States	Herbert Herman Cancer Center /ID# 130239	Lansing	Michigan
United States	LA Hem-Oncology Med Group /ID# 131639	Los Angeles	California
United States	University of Louisville /ID# 130217	Louisville	Kentucky
United States	University of South Alabama /ID# 131518	Mobile	Alabama
United States	Univ Oklahoma HSC /ID# 132888	Oklahoma City	Oklahoma
United States	Albert Einstein Medical Center /ID# 134498	Philadelphia	Pennsylvania
United States	Allegheny General Hospital /ID# 134049	Pittsburgh	Pennsylvania
United States	Washington University-School of Medicine /ID# 131651	Saint Louis	Missouri
United States	Univ Texas HSC San Antonio /ID# 132972	San Antonio	Texas
United States	St Jude Hospital dba St Joseph /ID# 132943	Santa Rosa	California
United States	Highlands Oncology Group /ID# 131250	Springdale	Arkansas
United States	Icri /Id# 132942	Whittier	California

Sponsors (1)

Lead Sponsor	Collaborator
AbbVie

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Canada,  Czechia,  Denmark,  Finland,  Germany,  Hungary,  Israel,  Japan,  Korea, Republic of,  Netherlands,  New Zealand,  Russian Federation,  South Africa,  Spain,  Taiwan,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Survival (OS) in the Lung Subtype Panel Positive Subgroup	Overall survival is defined as the time from the date that the participant was randomized to the date of the participant's death. Overall survival was estimated using Kaplan-Meier methodology. Participants still alive at the data cut-off date were censored at the date they were last known to be alive.	From randomization up to the data cut-off date of 15 July 2019; median follow-up time was 44.5 and 45.3 months in LSP+ participants for the investigator's choice chemotherapy and veliparib + C/P arms, respectively.
Secondary	Progression Free Survival (PFS) in the Lung Subtype Panel Positive Subgroup	Progression-free survival is defined as the time from the date of randomization to the date of disease progression (PD) per Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1 or death (all causes of mortality), whichever occurred first.; PD: At least a 20% increase in the size of target lesions, taking as reference the smallest size recorded since the treatment started (Baseline or after) with an absolute increase of at least 5 mm, the appearance of one or more new lesions, or unequivocal progression of existing non-target lesions.; PFS was estimated using Kaplan-Meier methodology. Participants who did not have an event of disease progression or had not died on or before the cutoff date were censored at the date of their last disease progression assessment on or before the cut-off date. Any PD and death occurring > 26 weeks and > 12 weeks after the previous assessment, respectively, were excluded and patients were censored at last assessment before PD or death.	From randomization up to the data cut-off date of 15 July 2019; the median follow-up time was 44.5 and 45.3 months in LSP+ participants for the investigator's choice chemotherapy and veliparib + C/P arms, respectively.
Secondary	Objective Response Rate (ORR) in the Lung Subtype Panel Positive Subgroup	Objective response rate is defined as the percentage of participants with a complete response (CR) or partial response (PR) per Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1 criteria. Response must have been confirmed at a consecutive assessment 28 days or more after the assessment at which response was first observed.; CR: The disappearance of all target and non-target lesions and no new lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm.; PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the Baseline sum diameters, persistence of one or more non-target lesion(s) and/or maintenance of tumor marker level above the normal limits, or any new lesions.	Assessed on Day 1 of Cycles 3 and 5 then every 9 weeks for 1 year or until maintenance therapy was discontinued, then every 12 weeks until radiographic progression or death; median time on follow-up was 5.2 and 6.3 months in each group, respectively.
Secondary	Overall Survival in All Participants	Overall survival is defined as the time from the date that the participant was randomized to the date of the participant's death. OS was estimated using Kaplan-Meier methodology. Participants still alive at the data cut-off date were censored at the date they were last known to be alive.	From randomization up to the data cut-off date of 15 July 2019; the median OS follow-up time was 45.4 and 44.6 months in all participants for the investigator's choice chemotherapy and veliparib + C/P arms, respectively.
Secondary	Progression Free Survival (PFS) in All Participants	Progression-free survival is defined as the time from the date of randomization to the date of disease progression (PD) per RECIST version 1.1 or death (all causes of mortality), whichever occurred first.; PD: At least a 20% increase in the size of target lesions, taking as reference the smallest size recorded since the treatment started (Baseline or after) with an absolute increase of at least 5 mm, the appearance of one or more new lesions, or unequivocal progression of existing non-target lesions.; PFS was estimated using Kaplan-Meier methodology. Participants who did not have an event of disease progression or had not died on or before the cut-off date were censored at the date of their last disease progression assessment on or before the cut-off date. Any PD and death occurring > 26 weeks and > 12 weeks after the previous assessment, respectively, were excluded and patients were censored at last assessment before PD or death.	From randomization up to the data cut-off date of 15 July 2019; the median follow-up time was 45.4 and 44.6 months in all participants for the investigator's choice chemotherapy and veliparib + C/P arms, respectively.
Secondary	Objective Response Rate (ORR) in All Participants	Objective response rate is defined as the percentage of participants with a complete response (CR) or partial response (PR) per RECIST version 1.1 criteria. Response must have been confirmed at a consecutive assessment 28 days or more after the assessment at which response was first observed.; CR: The disappearance of all target and non-target lesions and no new lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm.; PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the Baseline sum diameters, persistence of one or more non-target lesion(s) and/or maintenance of tumor marker level above the normal limits, or any new lesions.	Assessed on Day 1 of Cycles 3 and 5 then every 9 weeks for 1 year or until maintenance therapy was discontinued, then every 12 weeks until radiographic progression or death; median time on follow-up was 6.7 and 5.9 months in each group, respectively.