Dose Escalation and Double-blind Study of Veliparib in Combination With Carboplatin and Etoposide in Treatment-naive Extensive Stage Disease Small Cell Lung Cancer

NCT ID: NCT02289690

Last Updated: 2020-05-14

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 221 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-10-13
• Study Completion Date: 2019-04-17

Brief Summary

The study seeks to assess the efficacy of veliparib (ABT-888) in combination with carboplatin and etoposide in participants with extensive disease small cell lung cancer (ED SCLC).

Detailed Description

This is a Phase 1, open-label, dose-escalation/Phase 2 randomized double-blind study of veliparib in combination with carboplatin and etoposide and maintenance veliparib monotherapy.

Participants in Phase 1 will be sequentially assigned to ascending dose levels of veliparib in combination with standard carboplatin/etoposide regimen for up to four 21-day cycles based on the observed toxicities. The study design for Phase 1 will follow a traditional "3 + 3" dose-escalation protocol.

Once the veliparib recommended Phase 2 dose (RPTD) and schedule is determined, enrollment into Phase 2 will begin. Participants from the Phase 1 dose-escalation portion of the study are not eligible for enrollment into the Phase 2 portion. Participants in Phase 2 will be randomized in a 1:1:1 ratio to carboplatin, etoposide, placebo followed by placebo maintenance (Arm C), or carboplatin, etoposide, veliparib followed by either veliparib (Arm A) or placebo (Arm B) maintenance. Randomization for Phase 2 will be stratified by baseline lactate dehydrogenase (LDH) level (> upper limit of normal [ULN] vs. ≤ ULN), and gender.

Conditions

Small Cell Lung Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Phase 1: Veliparib + Carboplatin + Etoposide

Participants in Phase 1 will be sequentially assigned to ascending dose levels of veliparib in combination with carboplatin/etoposide for up to four 21-day cycles.

Participants without evidence of disease progression will continue on veliparib monotherapy at 400 mg BID continuous dosing (21-day cycles) until disease progression or unacceptable toxicity.

Group Type: EXPERIMENTAL

Veliparib

Intervention Type: DRUG

Capsules administered orally twice a day according to the dosing schedule.

Carboplatin

Intervention Type: DRUG

Administered by intravenous infusion on Day 1 of each 21-day cycle over approximately 30 minutes at a target area under the curve (AUC) 5 mg/mL\*minute.

Etoposide

Intervention Type: DRUG

Administered by intravenous infusion on Days 1 to 3 of every 21-day cycle over approximately 60 minutes at 100 mg/m².

Phase 2: Veliparib + Carboplatin + Etoposide -> Veliparib

Participants will receive veliparib 240 mg in combination with carboplatin/etoposide for four to six 21-day cycles followed by veliparib monotherapy at 400 mg BID continuous dosing (21-day cycles) until disease progression or unacceptable toxicity.

Group Type: EXPERIMENTAL

Veliparib

Intervention Type: DRUG

Capsules administered orally twice a day according to the dosing schedule.

Carboplatin

Intervention Type: DRUG

Administered by intravenous infusion on Day 1 of each 21-day cycle over approximately 30 minutes at a target area under the curve (AUC) 5 mg/mL\*minute.

Etoposide

Intervention Type: DRUG

Administered by intravenous infusion on Days 1 to 3 of every 21-day cycle over approximately 60 minutes at 100 mg/m².

Phase 2: Veliparib + Carboplatin + Etoposide -> Placebo

Participants will receive veliparib 240 mg in combination with carboplatin/etoposide for four to six 21-day cycles followed by placebo monotherapy continuous dosing (21-day cycles) until disease progression or unacceptable toxicity occurs.

Group Type: EXPERIMENTAL

Veliparib

Intervention Type: DRUG

Capsules administered orally twice a day according to the dosing schedule.

Carboplatin

Intervention Type: DRUG

Administered by intravenous infusion on Day 1 of each 21-day cycle over approximately 30 minutes at a target area under the curve (AUC) 5 mg/mL\*minute.

Etoposide

Intervention Type: DRUG

Administered by intravenous infusion on Days 1 to 3 of every 21-day cycle over approximately 60 minutes at 100 mg/m².

Placebo

Intervention Type: DRUG

Placebo to veliparib administered orally twice a day according to the dosing schedule.

Phase 2: Placebo + Carboplatin + Etoposide -> Placebo

Participants will receive placebo in combination with carboplatin/etoposide for four to six 21-day cycles followed by placebo monotherapy continuous dosing (21-day cycles) until disease progression or unacceptable toxicity occurs.

Group Type: ACTIVE_COMPARATOR

Carboplatin

Intervention Type: DRUG

Administered by intravenous infusion on Day 1 of each 21-day cycle over approximately 30 minutes at a target area under the curve (AUC) 5 mg/mL\*minute.

Etoposide

Intervention Type: DRUG

Administered by intravenous infusion on Days 1 to 3 of every 21-day cycle over approximately 60 minutes at 100 mg/m².

Placebo

Intervention Type: DRUG

Placebo to veliparib administered orally twice a day according to the dosing schedule.

Interventions

Veliparib

Capsules administered orally twice a day according to the dosing schedule.

Intervention Type: DRUG

Carboplatin

Administered by intravenous infusion on Day 1 of each 21-day cycle over approximately 30 minutes at a target area under the curve (AUC) 5 mg/mL\*minute.

Intervention Type: DRUG

Etoposide

Administered by intravenous infusion on Days 1 to 3 of every 21-day cycle over approximately 60 minutes at 100 mg/m².

Intervention Type: DRUG

Placebo

Placebo to veliparib administered orally twice a day according to the dosing schedule.

Intervention Type: DRUG

Other Intervention Names

ABT-888; VP-16

Eligibility Criteria

Inclusion Criteria

1. Subject with histologically or cytologically confirmed extensive-stage disease SCLC which is newly diagnosed and chemotherapy naive

2. Phase 1 ONLY: histologically or cytologically confirmed advanced/metastatic solid tumors for which carboplatin/etoposide treatment is considered appropriate.

3. Subject in Phase 2 only: must have measurable disease per RECIST 1.1.

4. Subjects with ED SCLC must consent to provide available archived formalin fixed paraffin embedded (FFPE) tissue sample of SCLC lesion (primary or metastatic) for central review and biomarker analysis.

5. Subject has an Eastern Cooperative Oncology Group (ECOG) performance score of 0 to 1.

6. Subject must have adequate hematologic, renal and hepatic function.

Exclusion Criteria

1. Phase 1 ONLY: Subject has had any prior anti-cancer therapy other than:

Hormonal, non-myelosuppressive, biologic, targeted, or immune therapy (must be completed ≥ 4 weeks prior to Cycle 1 Day -2).

One line of cytotoxic chemotherapy (must be completed ≥ 4 weeks prior to Cycle 1 Day -2).

Adjuvant/neoadjuvant radiotherapy (must be completed ≥ 12 months prior to Cycle 1 Day -2, with field not involving > 10% of bone marrow reserve).

2. Phase 2 ONLY: Subject has had any prior chemotherapy, radiotherapy, investigational anti-cancer agents or biologic therapy for the disease under study. Single non-target lesion irradiation with intent of symptom palliation is allowed if ≥ 4 weeks prior Cycle 1 Day -2.

3. Subject has current central nervous system (CNS) or leptomeningeal metastases or history of CNS or leptomeningeal metastases.

4. Subject has a history of seizures within 12 months of Cycle 1 Day-2 or diagnosed neurological condition placing subject at the increased risk of seizures.

5. Subject has received anti-cancer Chinese medicine or anti-cancer herbal remedies within 14 days prior to Cycle 1 Day-2.

6. Subject has had major surgery within 6 weeks prior to Cycle 1 Day-2 (subjects must have completely recovered from any previous surgery prior Cycle 1 Day-2).

7. Subject has clinically significant and uncontrolled major medical condition(s) including but not limited to:

• Uncontrolled nausea/vomiting/diarrhea;
• Active uncontrolled infection;
• History of hepatitis B (HBV) with surface antigen (HBsAg) positivity within 3 months prior to the date of informed consent for this study (if no test has been performed within 3 months, it must be done at screening);
• History of hepatitis C (HCV) with HCV ribonucleic acid (RNA) positivity within 3 months prior to the date of informed consent for this study (if no test has been performed within 3 months it must be done at screening);
• Symptomatic congestive heart failure (Yew York Heart Association [NYHA] class ≥ II);
• Unstable angina pectoris or cardiac arrhythmia (except atrial fibrillation);
• Psychiatric illness/social situation that would limit compliance with study requirements;
• Any other medical condition, which in the opinion of the Investigator, places the subject at an unacceptably high risk for toxicities.

8. The subject has a history of another active cancer within the past 3 years except cervical cancer in situ, in situ carcinoma of the bladder, squamous or basal cell carcinoma of the skin or another in situ cancer that is considered cured by the investigator (e.g., in situ prostate cancer, breast DCIS).

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 99 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

AbbVie

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

AbbVie Inc.

Role: STUDY_DIRECTOR

AbbVie

Locations

Mayo Clinic - Scottsdale /ID# 129127

Scottsdale, Arizona, United States

Univ of Colorado Cancer Center /ID# 129220

Aurora, Colorado, United States

Emory University Hospital /ID# 141682

Atlanta, Georgia, United States

Georgia Regents University /ID# 148567

Augusta, Georgia, United States

Northwestern University Feinberg School of Medicine /ID# 137088

Chicago, Illinois, United States

Herbert Herman Cancer Center /ID# 167020

Lansing, Michigan, United States

Gabrail Cancer Center Research /ID# 129216

Canton, Ohio, United States

Allegheny General Hospital /ID# 147328

Pittsburgh, Pennsylvania, United States

University of Texas MD Anderson Cancer Center /ID# 129213

Houston, Texas, United States

Southern Medical Day Care Ctr /ID# 155498

Wollongong, New South Wales, Australia

The Townsville Hospital /ID# 155499

Douglas, Queensland, Australia

Peninsula & South Eastern Haem /ID# 155497

Frankston, Victoria, Australia

Border Medical /ID# 157894

Wodonga, Victoria, Australia

Cliniques Universitaires Saint Luc /ID# 151024

Woluwe-Saint-Lambert, Brussels Capital, Belgium

CHU de Liege /ID# 151025

Liège, Liege, Belgium

UZ Antwerp /ID# 151026

Edegem, , Belgium

C.H.U.de Mons Borinage /ID# 151023

Mons, , Belgium

CHU UCL Namur /ID# 151022

Namur, , Belgium

University of Calgary /ID# 152544

Calgary, Alberta, Canada

Cross Cancer Institute /ID# 132883

Edmonton, Alberta, Canada

Juravinski Cancer Clinic /ID# 152543

Hamilton, Ontario, Canada

Hopital du Sacre Coeur Montreal /ID# 154436

Montreal, Quebec, Canada

Nemocnice Na Plesi s.r.o. /ID# 149825

Nová Ves pod Pleší, Pribram, Czechia

Nemocnice Novy Jicin /ID# 149838

Nový Jičín, , Czechia

Vitkovicka nemocnice a. s. /ID# 149839

Ostrava, , Czechia

Multiscan s.r.o. /ID# 150887

Pardubice, , Czechia

CHU Dupuytren /ID# 153622

Limoges, Franche-Comte, France

Centre Hospitalier Le Mans /ID# 158103

Le Mans, Sarthe, France

Centre Hosp Intercommunal de Creteil /ID# 157970

Créteil, Val-de-Marne, France

Orszagos Koranyi Pulmonologiai Intezet /ID# 151351

Budapest XII, Budapest, Hungary

Markusovszky Egyetemi Oktatókórház /ID# 158806

Szombathely, Vas County, Hungary

Debreceni Egyetem Klinikai Központ /ID# 151354

Debrecen, , Hungary

Veszprem Megyei Tudogyogyintez /ID# 158807

Farkasgyepű, , Hungary

Petz Aladar Megyei Oktato Korh /ID# 155352

Győr, , Hungary

Matrahaza Gyogyintezet /ID# 151355

Kékesteto, , Hungary

Fejer Megyei Szent Gyorgy Korh /ID# 151352

Székesfehérvár, , Hungary

Jasz-Nagykun-Szolnok Megyei /ID# 155090

Szolnok, , Hungary

Universitair Medisch Centrum Groningen /ID# 131252

Groningen, , Netherlands

Ziekenhuis St. Jansdal /ID# 151974

Harderwijk, , Netherlands

Atrium-Orbis Zuyderland Medisch Centrum /ID# 149830

Heerlen, , Netherlands

Erasmus Medisch Centrum /ID# 131251

Rotterdam, , Netherlands

Isala /ID# 151975

Zwolle, , Netherlands

S.C. Centrul de Oncologie Sf. Nectarie S.R.L. /ID# 161137

Craiova, Dolj, Romania

Oncocenter Oncologie Clinica S /ID# 151694

Timișoara, Timiș County, Romania

S.C. Radiotherapy Center Cluj /ID# 165137

Cluj-Napoca, , Romania

NN Blokhin Russian Cancer /ID# 152329

Moscow, Moscow, Russia

Sverdlovsk Regional Oncology Center Dispensary /ID# 152328

Yekaterinburg, Sverdlovsk Oblast, Russia

Belgorod Oncology Dispensary /ID# 152330

Belgorod, , Russia

Univercity Headache Clynic,LTD /ID# 161708

Moscow, , Russia

Murmansk RCH P.A. Bayandina /ID# 152331

Murmansk, , Russia

Road Hospital Open Joint Stock Company Russian Railways /ID# 152731

Saint Petersburg, , Russia

Ogarev Mordovia State Univ /ID# 152327

Saransk, , Russia

Dong-A University Hospital /ID# 153187

Busan, Busan Gwang Yeogsi, South Korea

Chungbuk National Univ Hosp /ID# 153186

Cheongju-si, , South Korea

Chonnam National University Hwasun Hospital /ID# 153188

Jeonnam, , South Korea

Asan Medical Center /ID# 153185

Seoul, , South Korea

Hospital Stanta Creu i Sant Pau /ID# 151254

Barcelona, , Spain

Hosp Univ Quiron Dexues /ID# 130302

Barcelona, , Spain

Hospital Universitario Gregori /ID# 164982

Madrid, , Spain

Hosp Univ 12 de Octubre /ID# 151252

Madrid, , Spain

Hosp Univ Madrid Sanchinarro /ID# 130301

Madrid, , Spain

Hosp Univ Puerta de Hierro Maj /ID# 151253

Majadahonda, , Spain

Countries

United States; Australia; Belgium; Canada; Czechia; France; Hungary; Netherlands; Romania; Russia; South Korea; Spain

References

Atrafi F, Groen HJM, Byers LA, Garralda E, Lolkema MP, Sangha RS, Viteri S, Chae YK, Camidge DR, Gabrail NY, Hu B, Tian T, Nuthalapati S, Hoening E, He L, Komarnitsky P, Calles A. A Phase I Dose-Escalation Study of Veliparib Combined with Carboplatin and Etoposide in Patients with Extensive-Stage Small Cell Lung Cancer and Other Solid Tumors. Clin Cancer Res. 2019 Jan 15;25(2):496-505. doi: 10.1158/1078-0432.CCR-18-2014. Epub 2018 Oct 16.

Reference Type: RESULT

PMID: 30327308 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2014-001764-35

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

M14-361

Identifier Type: -

Identifier Source: org_study_id