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OpenTrials
Completed

NCT Number: NCT02944396

Study of Veliparib in Combination With Nivolumab and Platinum Doublet Chemotherapy in Participants With Metastatic or Advanced Non-Small Cell Lung Cancer (NSCLC)

This study seeks to establish the recommended Phase 2 dose (RPTD) of veliparib in combination with nivolumab and platinum doublet chemotherapy (carboplatin/paclitaxel or carboplatin/pemetrexed) (Phase 1 portion) and to assess whether the addition of nivolumab to veliparib in combination with platinum doublet chemotherapy results will improve progression free survival (PFS) compared to veliparib with platinum doublet chemotherapy alone in participants with metastatic or advanced Non-small Cell Lung Cancer (NSCLC) (Phase 2 portion).

A strategy decision was made not to proceed to Phase 2 portion of this study due to change in standard of care.

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Key information

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

University of Alabama at Birmingham - Main /ID# 155135, Birmingham, Alabama, United States

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Participant must have a life expectancy greater than 12 weeks,
  • Participant must have cytologically or histologically confirmed Non-small Cell Lung Cancer (NSCLC).
  • Participant must have metastatic or advanced NSCLC (Stage IIIB or IV) that is not amenable to surgical resection or radiation or chemoradiation with curative intent at time of study screening.
  • Participant 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).
  • Participant must have resolution to Grade 1 or lower of any toxic effects (excepting alopecia) of the most recent therapy prior to Cycle 1 Day 2.
  • Participant must have an Eastern Cooperative Oncology Group (ECOG) Performance Score of 0 to 1.
  • Participant must have adequate bone marrow, renal, and hepatic function.

Exclusion criteria

  • Participant has received prior cytotoxic chemotherapy (including chemotherapy in combination with radiotherapy) for NSCLC, except for adjuvant or neoadjuvant therapy accompanied by surgery with curative intent that was completed one year prior to Cycle 1 Day -2.
  • Participant has received prior therapy with a Poly-(ADP-ribose)-Polymerase (PARP) inhibitor.
  • Participant has received prior treatment with any anti-programmed cell death protein-1 (anti-PD-1), or PD Ligand-1 (PD-L1) or PD Ligand-2 (PD-L2) agent or an antibody targeting other immunoregulatory receptors or mechanisms.
  • Participant has received radiation therapy to lung greater than 30 Gy within 6 months, or antineoplastic biologic therapy within 21 days, or major surgery within 21 days, or tyrosine kinase inhibitor therapy within 7 days, or palliative radiation within 7 days of the first dose of study medication.
  • Participant has untreated central nervous system (CNS) metastases.

Treatment and study plan

Pemetrexed

Drug

intravenous; administered on Day 1 via infusion in a 21-day cycle

Other names: Alimta

Nivolumab

Drug

intravenous; administered on Day 1 via infusion in a 21-day cycle

Other names: Opdivo

paclitaxel

Drug

intravenous; administered on Day 1 via infusion in a 21-day cycle

Other names: Taxol

Veliparib

Drug

oral capsule; varying doses administered on Days -2 to 5 in a 21-day cycle

Other names: ABT-888

carboplatin

Drug

intravenous; administered on Day 1 via infusion in a 21-day cycle

Other names: Paraplatin

Primary outcomes

  1. Progression-free survival (PFS)

    Time frame: Up to approximately 3.5 years

    PFS is defined as the number of days from the date of randomization to the date of earliest disease progression (radiographic progression per RECIST version 1.1 or clinical disease progression) or death. If the participant does not experience disease progression or death, then the data will be censored at the date of the last disease assessment.

  2. Recommended Phase 2 dose (RPTD) of veliparib (ABT-888) in combination with nivolumab and platinum doublet chemotherapy in participants with metastatic or advanced Non-Small Cell Lung Cancer (NSCLC).

    Time frame: Up to 6 weeks

Secondary outcomes

  1. Tmax for pemetrexed

    Time frame: Up to approximately 3 weeks

  2. AUC for nivolumab

    Time frame: Up to approximately 3.5 years

  3. Overall Survival (OS)

    Time frame: Up to approximately 3.5 years

    OS is defined as the number of days from the date of randomization to the date of death. For subjects who did not die, their data will be censored at the date of last study visit or the last known date to be alive, whichever is later.

  4. Tmax for nivolumab

    Time frame: Up to approximately 3.5 years

  5. AUC for pemetrexed

    Time frame: Up to approximately 3 weeks

  6. Time to Cmax (peak time, Tmax) for veliparib

    Time frame: Up to approximately 9 weeks

  7. Area under the plasma concentration-time curve (AUC) for veliparib

    Time frame: Up to approximately 9 weeks

  8. Maximum observed serum concentration (Cmax) of nivolumab anti-drug antibody (ADA)

    Time frame: Up to approximately 3.5 years

  9. Duration of Overall Response (DOR)

    Time frame: Up to approximately 3.5 years

    DOR is defined as the number of days from the date of first response (CR or PR) to the earliest documentation of progressive disease or death due to disease progression.

  10. Maximum observed plasma concentration (Cmax) for pemetrexed

    Time frame: Up to approximately 3 weeks

  11. Maximum observed plasma concentration (Cmax) for veliparib

    Time frame: Up to approximately 9 weeks

  12. Objective Response Rate (ORR)

    Time frame: Up to approximately 3.5 years

    ORR is defined as the proportion of the participants who have a complete response (CR) or partial response (PR).

Sponsors and collaborators

Lead sponsor

AbbVie

Industry

Registry information

Official study title

A Phase 1 Dose-Escalation and Phase 2 Randomized, Open-Label Study of Nivolumab and Veliparib in Combination With Platinum Doublet Chemotherapy in Subjects With Metastatic or Advanced Non-Small Cell Lung Cancer (NSCLC)

Important dates

Study start
2016
Primary completion
2019
Study completion
2019
First posted
Oct 25, 2016
Registry last updated
Oct 23, 2019

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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