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

Study at a glance

From the registry record, last updated by the sponsor on 14 May 2020. Recruitment status is as the sponsor reported it: confirm with the study team.

Official 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

ClinicalTrials.gov ID

NCT02289690

Acronym / sponsor ID

M14-361

Conditions

Small Cell Lung Cancer

Keywords

Extensive Stage Smal Cell Lung Cancer, ABT-888, Veliparib, PARP - Poly (ADP) ribose polymerase

Phase

Phase 1/2

Study type

Interventional

Recruitment status

Completed

Enrolment

221 participants (actual)

Lead sponsor

AbbVieIndustry (pharma, biotech, devices)

Study start

13 Oct 2014 (actual)

Primary completion

17 Apr 2019 (actual)

Study completion

17 Apr 2019 (actual)

First posted

13 Nov 2014 (estimated)

Results

Posted 14 May 2020

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose

Treatment

Allocation

Randomised

Intervention model

Sequential

Masking

Double blind (participant, investigator)

Number of arms

4

Who may qualify

Ages

18 to 99 years

Sex

All

Healthy volunteers

Not accepted

Age groups

Adult, Older adult

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Primary outcome

1. Phase 1: Number of Participants With Dose-limiting Toxicities (DLTs)

   Time frame: Cycle 1 Day -2 to pre-dose on Cycle 2 Day 1 (23 days)

   A DLT was defined as any of the following drug-related toxicities, graded according to the Common Toxicity Criteria for Adverse Events (CTCAE), V.4.0: 1. Events associated with treatment delay >14 days in initiating Cycle 2 therapy: Grade 4 thrombocytopenia, neutropenia, or febrile neutropenia, or Grade 3 febrile neutropenia with fever for > 7 days 2. Grade ≥ 3 non-hematologic toxicity with ≥ 2 grade increase from baseline and attributed to veliparib treatment, excluding nausea or vomiting for ≤ 48 hours or inadequately treated, electrolyte abnormalities resolving in ≤ 24 hours, hypersensitivity reactions or alopecia 3. Grade 2 non-hematologic toxicity of ≥ 2 grade increase from baseline, attributed to veliparib treatment requiring delay of >14 days in initiation of Cycle 2 4. Any toxicity of ≥ 2-grade increase from baseline, attributed to veliparib and requiring a dose modification in Cycle 1 or omission of carboplatin, >1 daily etoposide dose, or >30% veliparib doses in Cycle 1

2. Phase 1: Maximum Observed Plasma Concentration (Cmax) of Veliparib

   Time frame: Cycle 1 Day 1 predose and at 1, 2, 3, 5, 8, and 24 hours post-dose

   Plasma concentrations of veliparib were determined using a validated online solid-phase extraction followed by high-performance liquid chromatography with tandem mass spectrometric detection (HPLC LC-MS/MS). The lower limit of quantitation (LLOQ) for veliparib was established at ≥ 1.05 ng/mL.

3. Phase 1: Time to Maximum Observed Plasma Concentration (Tmax) of Veliparib

   Time frame: Cycle 1 Day 1 predose and at 1, 2, 3, 5, 8, and 24 hours post-dose

   Plasma concentrations of veliparib were determined using a validated online solid-phase extraction followed by high-performance liquid chromatography with tandem mass spectrometric detection (HPLC LC-MS/MS). The lower limit of quantitation (LLOQ) for veliparib was established at ≥ 1.05 ng/mL.

4. Phase 1: Area Under the Plasma Concentration-time Curve From Time 0 to 8 Hours Post-dose (AUC[0-8]) of Veliparib

   Time frame: Cycle 1 Day 1 predose and at 1, 2, 3, 5, 8, and 24 hours post-dose

   The area under the plasma concentration-time curve from time 0 to 8 hours post-dose for veliparib was estimated using non-compartmental methods.

5. Phase 1: Area Under the Plasma Concentration-time Curve From Time 0 to 12 Hours Post-dose (AUC[0-12]) of Veliparib

   Time frame: Cycle 1 Day 1 predose and at 1, 2, 3, 5, 8, and 24 hours post-dose

   The area under the plasma concentration-time curve from time 0 to 12 hours post-dose for veliparib was estimated using non-compartmental methods. AUC(0-12) was calculated by assuming the concentration at 12 hours post-dose was the same as the pre-dose concentration.

6. Phase 1: Dose-normalized Maximum Observed Plasma Concentration of Veliparib

   Time frame: Cycle 1 Day 1 predose and at 1, 2, 3, 5, 8, and 24 hours post-dose

   Plasma concentrations of veliparib were determined using a validated online solid-phase extraction followed by high-performance liquid chromatography with tandem mass spectrometric detection (HPLC LC-MS/MS). The lower limit of quantitation (LLOQ) for veliparib was established at ≥ 1.05 ng/mL. Dose normalized Cmax is calculated as Cmax / veliparib dose in mg.

7. Phase 1: Dose-normalized Area Under the Plasma Concentration-time Curve From Time 0 to 8 Hours Post-dose of Veliparib

   Time frame: Cycle 1 Day 1 predose and at 1, 2, 3, 5, 8, and 24 hours post-dose

   The area under the plasma concentration-time curve from time 0 to 8 hours post-dose for veliparib was estimated using non-compartmental methods. Dose normalized AUC(0-8) is calculated as AUC(0-8) / veliparib dose in mg.

8. Phase 1: Dose-normalized Area Under the Plasma Concentration-time Curve From Time 0 to 12 Hours Post-dose of Veliparib

   Time frame: Cycle 1 Day 1 predose and at 1, 2, 3, 5, 8, and 24 hours post-dose

   The area under the plasma concentration-time curve from time 0 to 12 hours post-dose for veliparib was estimated using non-compartmental methods. AUC(0-12) was calculated by assuming the concentration at 12 hours post-dose was the same as the pre-dose concentration. Dose normalized AUC(0-12) is calculated as AUC(0-12) / veliparib dose in mg.

9. Phase 1: Maximum Observed Plasma Concentration (Cmax) of Etoposide With and Without Veliparib

   Time frame: 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.

   Etoposide plasma concentrations were determined using liquid chromatography with tandem mass spectrometric detection with a lower limit of quantitation 160 ng/mL.

10. Phase 1: Time to Maximum Observed Plasma Concentration (Tmax) of Etoposide With and Without Veliparib

    Time frame: 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.

    Etoposide plasma concentrations were determined using liquid chromatography with tandem mass spectrometric detection with a lower limit of quantitation 160 ng/mL.

11. 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

    Time frame: 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.

    The area under the plasma concentration-time curve from 0 to the last measurable concentration (24 hours) of etoposide was estimated using using non-compartmental methods.

12. Phase 1: Area Under the Concentration-time Curve From Time 0 to Infinity (AUC[0-∞]) of Etoposide With and Without Veliparib

    Time frame: 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.

    The area under the plasma concentration-time curve from 0 to infinity for etoposide was estimated using using non-compartmental methods.

13. Phase 1: Terminal Phase Elimination Half-life (t1/2) of Etoposide With and Without Veliparib

    Time frame: 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.

    The terminal half-life of etoposide was estimated using using non-compartmental methods. Values reported represent the harmonic mean ± pseudo-standard deviation.

14. Phase 1: Dose-normalized Maximum Observed Plasma Concentration (Cmax) of Etoposide With and Without Veliparib

    Time frame: 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.

    Etoposide plasma concentrations were determined using liquid chromatography with tandem mass spectrometric detection with a lower limit of quantitation 160 ng/mL. Dose normalized Cmax is calculated as Cmax / etoposide dose in mg/m².

15. 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

    Time frame: 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.

    The area under the plasma concentration-time curve from 0 to the last measurable concentration (24 hours) of etoposide was estimated using using non-compartmental methods. Dose normalized AUC(0-t) is calculated as AUC(0-t) / etoposide dose in mg/m².

16. Phase 1: Dose-normalized Area Under the Concentration-time Curve From Time 0 to Infinity (AUC[0-∞]) of Etoposide With and Without Veliparib

    Time frame: 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.

    The area under the plasma concentration-time curve from 0 to infinity for etoposide was estimated using using non-compartmental methods. Dose normalized AUC(0-∞) is calculated as AUC(0-∞) / etoposide dose in mg/m².

17. Phase 2: Progression-free Survival

    Time frame: 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.

    Progression-free survival (PFS) is defined as the time from the date of randomization to the date of earliest radiographic disease progression or death provided no radiographic disease progression occurred. If a participant did not have an event of disease progression and had not died on or prior to the cutoff for PFS analysis, the participant's data was censored at the date of their last disease assessment or randomization date provided participant did not have any post-baseline disease assessment. Disease assessments were performed using computed tomography according to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1. Progressive Disease (PD) was defined as at least a 20% increase in the size of target lesions and an absolute increase of at least 5 mm taking as reference the smallest lesion size recorded since the treatment started (baseline or after), or the appearance of one or more new lesions.

Results and safety

Loading the posted results from ClinicalTrials.gov…

Research links

• Official record on ClinicalTrials.govLast updated by the sponsor 14 May 2020.
• Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
• Results publication: PubMed 30327308Atrafi 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.
• Individual participant dataSharing planned: Yes. 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.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

62 sites in 12 countries: see every site and its status.