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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02289690




Registration number
NCT02289690
Ethics application status
Date submitted
10/11/2014
Date registered
13/11/2014

Titles & IDs
Public title
Dose Escalation and Double-blind Study of Veliparib in Combination With Carboplatin and Etoposide in Treatment-naive Extensive Stage Disease Small Cell Lung Cancer
Scientific title
A Phase 1 Dose Escalation and Phase 2 Randomized Double-Blind Study of Veliparib in Combination With Carboplatin and Etoposide as a Therapy of Treatment-Naïve Extensive Stage Disease Small Cell Lung Cancer
Secondary ID [1] 0 0
2014-001764-35
Secondary ID [2] 0 0
M14-361
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Small Cell Lung Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lung - Mesothelioma
Cancer 0 0 0 0
Lung - Non small cell
Cancer 0 0 0 0
Lung - Small cell

Intervention/exposure
Study type
Interventional(has expanded access)
Description of intervention(s) / exposure
Treatment: Drugs - Veliparib
Treatment: Drugs - Carboplatin
Treatment: Drugs - Etoposide
Treatment: Drugs - Placebo

Experimental: 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.

Experimental: 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.

Experimental: 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.

Active comparator: 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.


Treatment: Drugs: Veliparib
Capsules administered orally twice a day according to the dosing schedule.

Treatment: Drugs: 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.

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

Treatment: Drugs: Placebo
Placebo to veliparib administered orally twice a day according to the dosing schedule.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Phase 1: Number of Participants With Dose-limiting Toxicities (DLTs)
Timepoint [1] 0 0
Cycle 1 Day -2 to pre-dose on Cycle 2 Day 1 (23 days)
Primary outcome [2] 0 0
Phase 1: Maximum Observed Plasma Concentration (Cmax) of Veliparib
Timepoint [2] 0 0
Cycle 1 Day 1 predose and at 1, 2, 3, 5, 8, and 24 hours post-dose
Primary outcome [3] 0 0
Phase 1: Time to Maximum Observed Plasma Concentration (Tmax) of Veliparib
Timepoint [3] 0 0
Cycle 1 Day 1 predose and at 1, 2, 3, 5, 8, and 24 hours post-dose
Primary outcome [4] 0 0
Phase 1: Area Under the Plasma Concentration-time Curve From Time 0 to 8 Hours Post-dose (AUC[0-8]) of Veliparib
Timepoint [4] 0 0
Cycle 1 Day 1 predose and at 1, 2, 3, 5, 8, and 24 hours post-dose
Primary outcome [5] 0 0
Phase 1: Area Under the Plasma Concentration-time Curve From Time 0 to 12 Hours Post-dose (AUC[0-12]) of Veliparib
Timepoint [5] 0 0
Cycle 1 Day 1 predose and at 1, 2, 3, 5, 8, and 24 hours post-dose
Primary outcome [6] 0 0
Phase 1: Dose-normalized Maximum Observed Plasma Concentration of Veliparib
Timepoint [6] 0 0
Cycle 1 Day 1 predose and at 1, 2, 3, 5, 8, and 24 hours post-dose
Primary outcome [7] 0 0
Phase 1: Dose-normalized Area Under the Plasma Concentration-time Curve From Time 0 to 8 Hours Post-dose of Veliparib
Timepoint [7] 0 0
Cycle 1 Day 1 predose and at 1, 2, 3, 5, 8, and 24 hours post-dose
Primary outcome [8] 0 0
Phase 1: Dose-normalized Area Under the Plasma Concentration-time Curve From Time 0 to 12 Hours Post-dose of Veliparib
Timepoint [8] 0 0
Cycle 1 Day 1 predose and at 1, 2, 3, 5, 8, and 24 hours post-dose
Primary outcome [9] 0 0
Phase 1: Maximum Observed Plasma Concentration (Cmax) of Etoposide With and Without Veliparib
Timepoint [9] 0 0
Cycle 1 Day 1 (coadministered with veliparib and carboplatin), and on Cycle 2 Day 1 (co-administered with carboplatin but in the absence of veliparib) at 55 minutes (5 minutes before the end of infusion) and 3, 5, 8, and 24 hours post-dose.
Primary outcome [10] 0 0
Phase 1: Time to Maximum Observed Plasma Concentration (Tmax) of Etoposide With and Without Veliparib
Timepoint [10] 0 0
Cycle 1 Day 1 (coadministered with veliparib and carboplatin), and on Cycle 2 Day 1 (co-administered with carboplatin but in the absence of veliparib) at 55 minutes (5 minutes before the end of infusion) and 3, 5, 8, and 24 hours post-dose.
Primary outcome [11] 0 0
Phase 1: Area Under the Concentration-time Curve From Time 0 to Time of Last Measurable Concentration (AUC[0-t]) of Etoposide With and Without Veliparib
Timepoint [11] 0 0
Cycle 1 Day 1 (coadministered with veliparib and carboplatin), and on Cycle 2 Day 1 (co-administered with carboplatin but in the absence of veliparib) at 55 minutes (5 minutes before the end of infusion) and 3, 5, 8, and 24 hours post-dose.
Primary outcome [12] 0 0
Phase 1: Area Under the Concentration-time Curve From Time 0 to Infinity (AUC[0-8]) of Etoposide With and Without Veliparib
Timepoint [12] 0 0
Cycle 1 Day 1 (coadministered with veliparib and carboplatin), and on Cycle 2 Day 1 (co-administered with carboplatin but in the absence of veliparib) at 55 minutes (5 minutes before the end of infusion) and 3, 5, 8, and 24 hours post-dose.
Primary outcome [13] 0 0
Phase 1: Terminal Phase Elimination Half-life (t1/2) of Etoposide With and Without Veliparib
Timepoint [13] 0 0
Cycle 1 Day 1 (coadministered with veliparib and carboplatin), and on Cycle 2 Day 1 (co-administered with carboplatin but in the absence of veliparib) at 55 minutes (5 minutes before the end of infusion) and 3, 5, 8, and 24 hours post-dose.
Primary outcome [14] 0 0
Phase 1: Dose-normalized Maximum Observed Plasma Concentration (Cmax) of Etoposide With and Without Veliparib
Timepoint [14] 0 0
Cycle 1 Day 1 (coadministered with veliparib and carboplatin), and on Cycle 2 Day 1 (co-administered with carboplatin but in the absence of veliparib) at 55 minutes (5 minutes before the end of infusion) and 3, 5, 8, and 24 hours post-dose.
Primary outcome [15] 0 0
Phase 1: Dose-normalized Area Under the Concentration-time Curve From Time 0 to Time of Last Measurable Concentration (AUC[0-t]) of Etoposide With and Without Veliparib
Timepoint [15] 0 0
Cycle 1 Day 1 (coadministered with veliparib and carboplatin), and on Cycle 2 Day 1 (co-administered with carboplatin but in the absence of veliparib) at 55 minutes (5 minutes before the end of infusion) and 3, 5, 8, and 24 hours post-dose.
Primary outcome [16] 0 0
Phase 1: Dose-normalized Area Under the Concentration-time Curve From Time 0 to Infinity (AUC[0-8]) of Etoposide With and Without Veliparib
Timepoint [16] 0 0
Cycle 1 Day 1 (coadministered with veliparib and carboplatin), and on Cycle 2 Day 1 (co-administered with carboplatin but in the absence of veliparib) at 55 minutes (5 minutes before the end of infusion) and 3, 5, 8, and 24 hours post-dose.
Primary outcome [17] 0 0
Phase 2: Progression-free Survival
Timepoint [17] 0 0
From randomization up to the date the 126th PFS event was reached; Median time on follow-up was 7.3, 7.1, and 8.9 months in each treatment group respectively.
Secondary outcome [1] 0 0
Phase 2: Overall Survival
Timepoint [1] 0 0
From randomization until the end of study; median time on follow-up was 10.0, 8.6, and 11.7 months in each treatment group respectively.
Secondary outcome [2] 0 0
Phase 2: Objective Response Rate
Timepoint [2] 0 0
Tumor assessments were performed every 6 weeks for the first 30 weeks and every 9 weeks thereafter until disease progression; median time on follow-up was 7.3, 7.1, and 8.9 months in each group respectively.
Secondary outcome [3] 0 0
Phase 1: Number of Participants With Adverse Events
Timepoint [3] 0 0
From first dose of any study drug to 30 days after the last dose; the median duration of treatment with veliparib across all groups in Phase 1 was 127.5 days.

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
99 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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).

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Other
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
13/10/2014
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
17/04/2019
Sample size
Target
Accrual to date
Final
221
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC
Recruitment hospital [1] 0 0
Southern Medical Day Care Ctr /ID# 155498 - Wollongong
Recruitment hospital [2] 0 0
The Townsville Hospital /ID# 155499 - Douglas
Recruitment hospital [3] 0 0
Peninsula & South Eastern Haem /ID# 155497 - Frankston
Recruitment hospital [4] 0 0
Border Medical /ID# 157894 - Wodonga
Recruitment postcode(s) [1] 0 0
2500 - Wollongong
Recruitment postcode(s) [2] 0 0
4814 - Douglas
Recruitment postcode(s) [3] 0 0
3199 - Frankston
Recruitment postcode(s) [4] 0 0
3690 - Wodonga
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
Colorado
Country [3] 0 0
United States of America
State/province [3] 0 0
Georgia
Country [4] 0 0
United States of America
State/province [4] 0 0
Illinois
Country [5] 0 0
United States of America
State/province [5] 0 0
Michigan
Country [6] 0 0
United States of America
State/province [6] 0 0
Ohio
Country [7] 0 0
United States of America
State/province [7] 0 0
Pennsylvania
Country [8] 0 0
United States of America
State/province [8] 0 0
Texas
Country [9] 0 0
Belgium
State/province [9] 0 0
Bruxelles-Capitale
Country [10] 0 0
Belgium
State/province [10] 0 0
Liege
Country [11] 0 0
Belgium
State/province [11] 0 0
Edegem
Country [12] 0 0
Belgium
State/province [12] 0 0
Mons
Country [13] 0 0
Belgium
State/province [13] 0 0
Namur
Country [14] 0 0
Canada
State/province [14] 0 0
Alberta
Country [15] 0 0
Canada
State/province [15] 0 0
Ontario
Country [16] 0 0
Canada
State/province [16] 0 0
Quebec
Country [17] 0 0
Czechia
State/province [17] 0 0
Pribram
Country [18] 0 0
Czechia
State/province [18] 0 0
Nový Jicín 1
Country [19] 0 0
Czechia
State/province [19] 0 0
Ostrava
Country [20] 0 0
Czechia
State/province [20] 0 0
Pardubice
Country [21] 0 0
France
State/province [21] 0 0
Franche-Comte
Country [22] 0 0
France
State/province [22] 0 0
Sarthe
Country [23] 0 0
France
State/province [23] 0 0
Val-de-Marne
Country [24] 0 0
Hungary
State/province [24] 0 0
Budapest
Country [25] 0 0
Hungary
State/province [25] 0 0
Vas
Country [26] 0 0
Hungary
State/province [26] 0 0
Debrecen
Country [27] 0 0
Hungary
State/province [27] 0 0
Farkasgyepu
Country [28] 0 0
Hungary
State/province [28] 0 0
Gyor
Country [29] 0 0
Hungary
State/province [29] 0 0
Kékesteto
Country [30] 0 0
Hungary
State/province [30] 0 0
Szekesfehervar
Country [31] 0 0
Hungary
State/province [31] 0 0
Szolnok
Country [32] 0 0
Korea, Republic of
State/province [32] 0 0
Busan Gwang Yeogsi
Country [33] 0 0
Korea, Republic of
State/province [33] 0 0
Cheongju
Country [34] 0 0
Korea, Republic of
State/province [34] 0 0
Jeonnam
Country [35] 0 0
Korea, Republic of
State/province [35] 0 0
Seoul
Country [36] 0 0
Netherlands
State/province [36] 0 0
Groningen
Country [37] 0 0
Netherlands
State/province [37] 0 0
Harderwijk
Country [38] 0 0
Netherlands
State/province [38] 0 0
Heerlen
Country [39] 0 0
Netherlands
State/province [39] 0 0
Rotterdam
Country [40] 0 0
Netherlands
State/province [40] 0 0
Zwolle
Country [41] 0 0
Romania
State/province [41] 0 0
Dolj
Country [42] 0 0
Romania
State/province [42] 0 0
Timis
Country [43] 0 0
Romania
State/province [43] 0 0
Cluj
Country [44] 0 0
Russian Federation
State/province [44] 0 0
Moskva
Country [45] 0 0
Russian Federation
State/province [45] 0 0
Sverdlovskaya Oblast
Country [46] 0 0
Russian Federation
State/province [46] 0 0
Belgorod
Country [47] 0 0
Russian Federation
State/province [47] 0 0
Moscow
Country [48] 0 0
Russian Federation
State/province [48] 0 0
Murmansk
Country [49] 0 0
Russian Federation
State/province [49] 0 0
Saransk
Country [50] 0 0
Russian Federation
State/province [50] 0 0
St. Petersburg
Country [51] 0 0
Spain
State/province [51] 0 0
Barcelona
Country [52] 0 0
Spain
State/province [52] 0 0
Madrid
Country [53] 0 0
Spain
State/province [53] 0 0
Majadahonda

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
AbbVie
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
AbbVie Inc.
Address 0 0
AbbVie
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
AbbVie is committed to responsible data sharing regarding the clinical trials we sponsor. This includes access to anonymized, individual and trial-level data (analysis data sets), as well as other information (e.g., protocols and clinical study reports), as long as the trials are not part of an ongoing or planned regulatory submission. This includes requests for clinical trial data for unlicensed products and indications.

Supporting document/s available: Study protocol, Statistical analysis plan (SAP), Clinical study report (CSR), Analytic code
When will data be available (start and end dates)?
Data requests can be submitted at any time and the data will be accessible for 12 months, with possible extensions considered.
Available to whom?
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.
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: https://www.abbvie.com/our-science/clinical-trials/clinical-trials-data-and-information-sharing/data-and-information-sharing-with-qualified-researchers.html


What supporting documents are/will be available?




Results publications and other study-related documents

TypeCitations or Other Details
Journal Atrafi F, Groen HJM, Byers LA, Garralda E, Lolkema... [More Details]


Results are available at https://clinicaltrials.gov/study/NCT02289690