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NCT02412371

A Study Evaluating the Efficacy and Tolerability of Veliparib in Combination With Paclitaxel/Carboplatin-Based Chemoradiotherapy Followed by Veliparib and Paclitaxel/Carboplatin Consolidation in Adults With Stage III Non-Small Cell Lung Cancer (NSCLC)

Terminated Phase 1, PHASE2 Results posted Last updated 22 July 2020
What this trial tests

Phase 1, PHASE2 trial testing Paclitaxel in Non-small Cell Lung Cancer Stage III in 48 participants. Terminated before completion.

Timeline
30 April 2015
Primary endpoint
5 August 2019
5 August 2019

Quick facts

Lead sponsorAbbVie
PhasePhase 1, PHASE2
StatusTerminated
Study typeINTERVENTIONAL
Allocationnon randomized
Designsequential
Maskingnone
Primary purposetreatment
Enrollment48
Start date30 April 2015
Primary completion5 August 2019
Estimated completion5 August 2019
Sites12 locations across United States

Drugs / interventions tested

Conditions studied

Sponsor

AbbVie — full company profile →

Who can join

18 and older, any sex, with Non-small Cell Lung Cancer Stage III. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Number of Participants With Dose-limiting Toxicities (DLTs) Primary · For Cohorts 1 - 5, from the start of veliparib dosing through 28 days after RT completion or until initiation of consolidation CT, approx. 10 weeks; For Cohort 6, 21 days from start of consolidation CT or until the start of cycle 2 consolidation therapy.

DLTs were defined as the following events considered treatment-related by the Investigator, graded per Common Terminology Criteria for Adverse Events (CTCAE) v4.0. * Radiation-induced myelopathy/myelitis or ≥ Grade (G) 3 cardiac toxicity * Radiation-related pneumonitis resulting in delay in RT, CT, or veliparib of \>3 weeks or early discontinuation (DC) of RT (total dose \<50 Gy) * ≥G4 esophagitis or esophagitis, dysphagia, and odynophagia requiring treatment interruption of \>7 days despite medical management, neutropenia for \>7 days or neutropenic fever or thrombocytopenia * ≥G2 seizure *

GroupValue95% CI
Veliparib 60 mg BID + CRT -> Veliparib 120 mg BID + CT0
Veliparib 80 mg BID + CRT -> Veliparib 120 mg BID + CT0
Veliparib 120 mg BID + CRT -> Veliparib 120 mg BID + CT0
Veliparib 200 mg BID + CRT -> Veliparib 120 mg BID + CT1
Veliparib 240 mg BID + CRT -> Veliparib 120 mg BID + CT0
Veliparib 240 mg BID + CRT -> Veliparib 240 mg BID + CT2
Objective Response Rate Secondary · Tumor assessments were performed prior to consolidation chemotherapy, 24 weeks after start of treatment, every 8 weeks until 1 year after start of treatment, and then every 12 weeks until disease progression; median time on follow-up was 11 months.

Objective response rate (ORR) is defined as the percentage of participants who have a confirmed complete response (CR) or partial response (PR) as assessed by the investigator using RECIST v1.1. Participants who did not meet complete response or partial response, including those who did not have post-baseline radiological assessments were considered as non-responders. Complete Response (CR): The disappearance of all target and non-target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm. Normalization of tumor marker level. All

GroupValue95% CI
Veliparib 60 mg BID + CRT -> Veliparib 120 mg BID + CT50.011.8 – 88.2
Veliparib 80 mg BID + CRT -> Veliparib 120 mg BID + CT50.015.7 – 84.3
Veliparib 120 mg BID + CRT -> Veliparib 120 mg BID + CT100.059.0 – 100
Veliparib 200 mg BID + CRT -> Veliparib 120 mg BID + CT62.524.5 – 91.5
Veliparib 240 mg BID + CRT -> Veliparib 120 mg BID + CT72.739.0 – 94.0
Veliparib 240 mg BID + CRT -> Veliparib 240 mg BID + CT0.00.0 – 70.8
Progression-free Survival Secondary · From first dose until end of study; maximum time on follow-up was approximately 46 months.

Progression-free survival (PFS) was defined as the time from first dose of study drug to the date of earliest radiographic disease progression per investigator assessment based on Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, or death, and was calculated using Kaplan-Meier methods. All radiographic disease progression was included regardless whether the event occurred while the participant was taking study drug or had previously discontinued study drug. Participants who did not experience radiographic disease progression or death were censored at the date of the last disease asse

GroupValue95% CI
Total19.69.7 – 32.6
Overall Survival Secondary · From first dose of study drug until end of study; maximum time on follow-up was approximately 46 months.

Overall survival (OS) was defined as the time from the participant's first dose of study drug to the date of death, and was calculated using Kaplan-Meier methods. Participants who did not die were censored at the date of last study visit or the last known date to be alive, whichever was later.

GroupValue95% CI
Total32.615.0 – NA
Duration of Overall Response (DOR) Secondary · Tumor assessments were performed prior to consolidation chemotherapy, 24 weeks after start of treatment, every 8 weeks until 1 year after start of treatment, and then every 12 weeks until disease progression; median time on follow-up was 11 months.

Duration of overall response was defined as time from the date of first response (CR or PR) to the earliest documentation of radiographic progressive disease or death due to disease progression, calculated using Kaplan-Meier methods. Participants who did not experience radiographic disease progression or death were censored at the date of the last disease assessment.

GroupValue95% CI
Total30.417.5 – NA

Adverse events — posted to ClinicalTrials.gov

Time frame: Adverse events were collected from the first dose of study drug to 30 days after the last dose of study drug; maximum duration of treatment was 14 weeks. Deaths were collected from the first dose of study drug through the end of study, up to 46 months.. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Veliparib 60 mg BID + CRT -> Veliparib 120 mg BID + CT
Serious: 2/7 (29%)
Deaths: 5/7
Veliparib 80 mg BID + CRT -> Veliparib 120 mg BID + CT
Serious: 5/9 (56%)
Deaths: 3/9
Veliparib 120 mg BID + CRT -> Veliparib 120 mg BID + CT
Serious: 4/7 (57%)
Deaths: 1/7
Veliparib 200 mg BID + CRT -> Veliparib 120 mg BID + CT
Serious: 3/8 (38%)
Deaths: 3/8
Veliparib 240 mg BID + CRT -> Veliparib 120 mg BID + CT
Serious: 3/12 (25%)
Deaths: 6/12
Veliparib 240 mg BID + CRT -> Veliparib 240 mg BID + CT
Serious: 2/5 (40%)
Deaths: 3/5

Serious adverse events (19 terms)

ReactionSystemVeliparib 60 mg BID + CRT …Veliparib 80 mg BID + CRT …Veliparib 120 mg BID + CRT…Veliparib 200 mg BID + CRT…Veliparib 240 mg BID + CRT…Veliparib 240 mg BID + CRT…
RADIATION PNEUMONITISInjury, poisoning and procedural complications
DEHYDRATIONMetabolism and nutrition disorders
FEBRILE NEUTROPENIABlood and lymphatic system disorders
CARDIAC ARRESTCardiac disorders
CARDIAC TAMPONADECardiac disorders
DIARRHOEAGastrointestinal disorders
NAUSEAGastrointestinal disorders
OESOPHAGEAL OBSTRUCTIONGastrointestinal disorders
OESOPHAGEAL STENOSISGastrointestinal disorders
OESOPHAGITISGastrointestinal disorders
VOMITINGGastrointestinal disorders
NON-CARDIAC CHEST PAINGeneral disorders
PYREXIAGeneral disorders
PNEUMONIAInfections and infestations
SEPSISInfections and infestations
BACK PAINMusculoskeletal and connective tissue disorders
HAEMOPTYSISRespiratory, thoracic and mediastinal disorders
PNEUMONIA ASPIRATIONRespiratory, thoracic and mediastinal disorders
PULMONARY OEDEMARespiratory, thoracic and mediastinal disorders
Other adverse events (179 terms — click to expand)

ReactionSystemVeliparib 60 mg BID + CRT …Veliparib 80 mg BID + CRT …Veliparib 120 mg BID + CRT…Veliparib 200 mg BID + CRT…Veliparib 240 mg BID + CRT…Veliparib 240 mg BID + CRT…
NAUSEAGastrointestinal disorders
NEUTROPENIABlood and lymphatic system disorders
THROMBOCYTOPENIABlood and lymphatic system disorders
OESOPHAGITISGastrointestinal disorders
LEUKOPENIABlood and lymphatic system disorders
DYSPHAGIAGastrointestinal disorders
FATIGUEGeneral disorders
ANAEMIABlood and lymphatic system disorders
LYMPHOPENIABlood and lymphatic system disorders
WEIGHT DECREASEDInvestigations
DECREASED APPETITEMetabolism and nutrition disorders
DEHYDRATIONMetabolism and nutrition disorders
COUGHRespiratory, thoracic and mediastinal disorders
CONSTIPATIONGastrointestinal disorders
DIARRHOEAGastrointestinal disorders
VOMITINGGastrointestinal disorders
HYPOKALAEMIAMetabolism and nutrition disorders
DIZZINESSNervous system disorders
HEADACHENervous system disorders
NON-CARDIAC CHEST PAINGeneral disorders
BRONCHITISInfections and infestations
PNEUMONIAInfections and infestations
HYPERGLYCAEMIAMetabolism and nutrition disorders
ANXIETYPsychiatric disorders
INSOMNIAPsychiatric disorders
DYSPNOEARespiratory, thoracic and mediastinal disorders
ALOPECIASkin and subcutaneous tissue disorders
DRY MOUTHGastrointestinal disorders
GASTROOESOPHAGEAL REFLUX DISEASEGastrointestinal disorders
ODYNOPHAGIAGastrointestinal disorders
CHILLSGeneral disorders
PERIPHERAL SWELLINGGeneral disorders
RADIATION SKIN INJURYInjury, poisoning and procedural complications
HYPOALBUMINAEMIAMetabolism and nutrition disorders
HYPOMAGNESAEMIAMetabolism and nutrition disorders
HYPONATRAEMIAMetabolism and nutrition disorders
ARTHRALGIAMusculoskeletal and connective tissue disorders
MYALGIAMusculoskeletal and connective tissue disorders
PAIN IN EXTREMITYMusculoskeletal and connective tissue disorders
DYSGEUSIANervous system disorders

Most-reported serious reactions: RADIATION PNEUMONITIS, DEHYDRATION, FEBRILE NEUTROPENIA, CARDIAC ARREST, CARDIAC TAMPONADE, DIARRHOEA, NAUSEA, OESOPHAGEAL OBSTRUCTION.

Data from ClinicalTrials.gov NCT02412371 adverse events section.

Sponsor's own description

This study seeks to establish * the recommended Phase 2 dose (RPTD) of veliparib in combination with concurrent paclitaxel/carboplatin-based chemoradiotherapy (CRT) and consolidation with paclitaxel/carboplatin-based chemotherapy (Phase 1 portion), and * to assess whether the addition of oral veliparib versus placebo to paclitaxel/carboplatin-based chemoradiotherapy with paclitaxel/carboplatin consolidation will improve progression-free survival (PFS) in adults with Stage III non-small cell lung cancer (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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. PARP inhibitor resistance: the underlying mechanisms and clinical implications.
    Li H, Liu ZY, Wu N, Chen YC, et al · · 2020 · cited 379× · PMID 32563252 · DOI 10.1186/s12943-020-01227-0
  2. Combination Platinum-based and DNA Damage Response-targeting Cancer Therapy: Evolution and Future Directions.
    Basourakos SP, Li L, Aparicio AM, Corn PG, et al · · 2017 · cited 91× · PMID 27978798 · DOI 10.2174/0929867323666161214114948
  3. Emerging therapeutic agents for lung cancer.
    Dholaria B, Hammond W, Shreders A, Lou Y. · · 2016 · cited 66× · PMID 27938382 · DOI 10.1186/s13045-016-0365-z
  4. Perspectives on the combination of radiotherapy and targeted therapy with DNA repair inhibitors in the treatment of pancreatic cancer.
    Yang SH, Kuo TC, Wu H, Guo JC, et al · · 2016 · cited 24× · PMID 27621574 · DOI 10.3748/wjg.v22.i32.7275
  5. A Dose-finding Study Followed by a Phase II Randomized, Placebo-controlled Trial of Chemoradiotherapy With or Without Veliparib in Stage III Non-small-cell Lung Cancer: SWOG 1206 (8811).
    Argiris A, Miao J, Cristea MC, Chen AM, et al · · 2021 · cited 21× · PMID 33745865 · DOI 10.1016/j.cllc.2021.02.009
  6. Advances in molecular targeted therapies to increase efficacy of (chemo)radiation therapy.
    Viktorsson K, Rieckmann T, Fleischmann M, Diefenhardt M, et al · · 2023 · cited 19× · PMID 37041372 · DOI 10.1007/s00066-023-02064-y
  7. Delivering on the promise: poly ADP ribose polymerase inhibition as targeted anticancer therapy.
    OʼSullivan Coyne G, Chen A, Kummar S. · · 2015 · cited 18× · PMID 26447876 · DOI 10.1097/cco.0000000000000238
  8. Advancing cancer therapy: new frontiers in targeting DNA damage response.
    Qian J, Liao G, Chen M, Peng RW, et al · · 2024 · cited 16× · PMID 39372203 · DOI 10.3389/fphar.2024.1474337

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