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NCT02305758

Study Comparing Veliparib Plus FOLFIRI Versus Placebo Plus FOLFIRI With or Without Bevacizumab in Previously Untreated Metastatic Colorectal Cancer

Completed Phase 2 Results posted Last updated 20 November 2018
What this trial tests

Phase 2 trial testing Veliparib in Untreated Metastatic Colorectal Cancer in 130 participants. Completed in 22 September 2017.

Timeline
2 December 2014
Primary endpoint
22 September 2017
22 September 2017

Quick facts

Lead sponsorAbbVie
PhasePhase 2
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingdouble
Primary purposetreatment
Enrollment130
Start date2 December 2014
Primary completion22 September 2017
Estimated completion22 September 2017

Drugs / interventions tested

Conditions studied

Sponsor

AbbVie — full company profile →

Who can join

Adults 18 to 99, any sex, with Untreated Metastatic Colorectal Cancer. 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.

Progression-Free Survival (PFS): Time to Event Primary · Every 8 weeks from Cycle 1, Day 1 until radiographic progression was observed. The maximum observed follow up duration at the progression-free survival analysis time was 579 days.

PFS was defined as the number of days from the date the participant was randomized to the date the participant experienced an event of disease progression or death, whichever occurred first. All events of disease progression were included, whether the participant was still taking or had discontinued study drug. Events of death were included for participants who had not experienced an event of disease progression, if the death occurred within 8 weeks of the last evaluable disease progression assessment. If the participant did not have an event of disease progression and the participant had not

25th Quartile
GroupValue95% CI
Veliparib + Modified FOLFIRI ± Bevacizumab221120 – 295
Placebo + FOLFIRI ± Bevacizumab213121 – 233
50th Quartile
GroupValue95% CI
Veliparib + Modified FOLFIRI ± Bevacizumab361289 – 453
Placebo + FOLFIRI ± Bevacizumab337233 – 421
75th Quartile
GroupValue95% CI
Veliparib + Modified FOLFIRI ± Bevacizumab534453 – NA
Placebo + FOLFIRI ± Bevacizumab512421 – NA
Overall Survival (OS): Time to Event Secondary · Survival information was to be collected 4 wks after the last study visit, continuing every 4 wks for 1 yr, then every 8 wks for up to 2 more yrs or until death. The maximum observed follow up duration at the overall survival analysis time was 914 days.

Overall survival was defined as the number of days from the date that the participant was randomized to the date of the participant's death. All events of death were included, regardless of whether the event occurred while the participant was still taking or had discontinued study drug. If a participant had not died, the data were censored at the date last known to be alive. The OS distribution was estimated using Kaplan-Meier methodology. Point estimates and 95% confidence intervals (95% CIs) for the OS distribution quartiles are provided.

25th Quartile
GroupValue95% CI
Veliparib + Modified FOLFIRI ± Bevacizumab557391 – 616
Placebo + FOLFIRI ± Bevacizumab512326 – 655
50th Quartile
GroupValue95% CI
Veliparib + Modified FOLFIRI ± Bevacizumab770609 – NA
Placebo + FOLFIRI ± Bevacizumab811678 – NA
75th Quartile
GroupValue95% CI
Veliparib + Modified FOLFIRI ± BevacizumabNA784 – NA
Placebo + FOLFIRI ± BevacizumabNA811 – NA
Objective Response Rate (ORR) Secondary · Per protocol, post-baseline tumor assessment was conducted every 8 weeks from Cycle 1 Day 1 until radiographic progression. The maximum observed follow up duration at the progression-free survival analysis time was 579 days.

ORR was defined as the proportion of participants with a complete (CR) or partial response (PR) based on Response Evaluation Criteria in Solid Tumors (RECIST, version 1.1) for target lesions, assessed by computed tomography (CT). Complete response (CR) was defined as disappearance of all target lesions; partial response (PR) ≥30% decrease in the the sum of diameters of target lesions, taking as reference the baseline sum diameters. For participants who underwent surgery, ORR was not evaluated after surgery.

GroupValue95% CI
Veliparib + Modified FOLFIRI ± Bevacizumab37
Placebo + FOLFIRI ± Bevacizumab40

Adverse events — posted to ClinicalTrials.gov

Time frame: Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) were collected from the time of veliparib/placebo administration until 30 days after the last dose of veliparib/placebo (up to 396 days).. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Veliparib + Modified FOLFIRI ± Bevacizumab
Serious: 30/65 (46%)
Deaths: 27/65
Placebo + FOLFIRI ± Bevacizumab
Serious: 33/65 (51%)
Deaths: 27/65

Serious adverse events (66 terms)

ReactionSystemVeliparib + Modified FOLFI…Placebo + FOLFIRI ± Bevaci…
DIARRHOEAGastrointestinal disorders
FEBRILE NEUTROPENIABlood and lymphatic system disorders
INTESTINAL OBSTRUCTIONGastrointestinal disorders
NEUTROPENIABlood and lymphatic system disorders
CARDIAC ARRESTCardiac disorders
ABDOMINAL PAINGastrointestinal disorders
LARGE INTESTINAL OBSTRUCTIONGastrointestinal disorders
VOMITINGGastrointestinal disorders
PYREXIAGeneral disorders
BILE DUCT STENOSISHepatobiliary disorders
PNEUMONIAInfections and infestations
MALIGNANT NEOPLASM PROGRESSIONNeoplasms benign, malignant and unspecified (incl cysts and polyps)
DYSPNOEARespiratory, thoracic and mediastinal disorders
PULMONARY EMBOLISMRespiratory, thoracic and mediastinal disorders
ATRIAL FLUTTERCardiac disorders
LEFT VENTRICULAR DYSFUNCTIONCardiac disorders
MYOCARDIAL ISCHAEMIACardiac disorders
TACHYARRHYTHMIACardiac disorders
TACHYCARDIACardiac disorders
CONSTIPATIONGastrointestinal disorders
ENTERITISGastrointestinal disorders
GASTROINTESTINAL OBSTRUCTIONGastrointestinal disorders
INTESTINAL PERFORATIONGastrointestinal disorders
INTRA-ABDOMINAL FLUID COLLECTIONGastrointestinal disorders
NAUSEAGastrointestinal disorders
Other adverse events (60 terms — click to expand)

ReactionSystemVeliparib + Modified FOLFI…Placebo + FOLFIRI ± Bevaci…
NEUTROPENIABlood and lymphatic system disorders
NAUSEAGastrointestinal disorders
DIARRHOEAGastrointestinal disorders
VOMITINGGastrointestinal disorders
ANAEMIABlood and lymphatic system disorders
FATIGUEGeneral disorders
ALOPECIASkin and subcutaneous tissue disorders
ABDOMINAL PAINGastrointestinal disorders
CONSTIPATIONGastrointestinal disorders
DECREASED APPETITEMetabolism and nutrition disorders
EPISTAXISRespiratory, thoracic and mediastinal disorders
ASTHENIAGeneral disorders
STOMATITISGastrointestinal disorders
MUCOSAL INFLAMMATIONGeneral disorders
LEUKOPENIABlood and lymphatic system disorders
PYREXIAGeneral disorders
DYSGEUSIANervous system disorders
HYPOKALAEMIAMetabolism and nutrition disorders
HEADACHENervous system disorders
INSOMNIAPsychiatric disorders
HYPERGLYCAEMIAMetabolism and nutrition disorders
HYPERTENSIONVascular disorders
ABDOMINAL PAIN UPPERGastrointestinal disorders
BACK PAINMusculoskeletal and connective tissue disorders
DYSPNOEARespiratory, thoracic and mediastinal disorders
OEDEMA PERIPHERALGeneral disorders
PERIPHERAL SENSORY NEUROPATHYNervous system disorders
COUGHRespiratory, thoracic and mediastinal disorders
URINARY TRACT INFECTIONInfections and infestations
VIRAL UPPER RESPIRATORY TRACT INFECTIONInfections and infestations
WEIGHT DECREASEDInvestigations
DEHYDRATIONMetabolism and nutrition disorders
PULMONARY EMBOLISMRespiratory, thoracic and mediastinal disorders
BRONCHITISInfections and infestations
UPPER RESPIRATORY TRACT INFECTIONInfections and infestations
ARTHRALGIAMusculoskeletal and connective tissue disorders
MYALGIAMusculoskeletal and connective tissue disorders
PARAESTHESIANervous system disorders
DYSURIARenal and urinary disorders
HAEMATURIARenal and urinary disorders

Most-reported serious reactions: DIARRHOEA, FEBRILE NEUTROPENIA, INTESTINAL OBSTRUCTION, NEUTROPENIA, CARDIAC ARREST, ABDOMINAL PAIN, LARGE INTESTINAL OBSTRUCTION, VOMITING.

Data from ClinicalTrials.gov NCT02305758 adverse events section.

Sponsor's own description

This was a blinded, randomized, placebo-controlled Phase 2 multicenter study evaluating the efficacy and tolerability of veliparib plus irinotecan, fluorouracil, and leucovorin chemotherapy regimen (FOLFIRI) compared to placebo plus FOLFIRI in participants with previously untreated metastatic colorectal cancer. Participants could also have been treated with bevacizumab at the discretion of the Investigator.

Publications & conference data

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

  1. Exploiting DNA repair defects in colorectal cancer.
    Reilly NM, Novara L, Di Nicolantonio F, Bardelli A. · · 2019 · cited 96× · PMID 30714316 · DOI 10.1002/1878-0261.12467
  2. Targeting Oxidatively Induced DNA Damage Response in Cancer: Opportunities for Novel Cancer Therapies.
    Davalli P, Marverti G, Lauriola A, D'Arca D. · · 2018 · cited 92× · PMID 29770165 · DOI 10.1155/2018/2389523
  3. Inherited DNA-Repair Defects in Colorectal Cancer.
    AlDubayan SH, Giannakis M, Moore ND, Han GC, et al · · 2018 · cited 85× · PMID 29478780 · DOI 10.1016/j.ajhg.2018.01.018
  4. Microenvironmental Reactive Oxygen Species in Colorectal Cancer: Involved Processes and Therapeutic Opportunities.
    Sorolla MA, Hidalgo I, Sorolla A, Montal R, et al · · 2021 · cited 42× · PMID 34680186 · DOI 10.3390/cancers13205037
  5. A phase 2 randomised study of veliparib plus FOLFIRI±bevacizumab versus placebo plus FOLFIRI±bevacizumab in metastatic colorectal cancer.
    Gorbunova V, Beck JT, Hofheinz RD, Garcia-Alfonso P, et al · · 2019 · cited 41× · PMID 30531832 · DOI 10.1038/s41416-018-0343-z
  6. Targeting the DNA Damage Response and DNA Repair Pathways to Enhance Radiosensitivity in Colorectal Cancer.
    Deng S, Vlatkovic T, Li M, Zhan T, et al · · 2022 · cited 40× · PMID 36230796 · DOI 10.3390/cancers14194874
  7. Molecular Analyses of Left- and Right-Sided Tumors in Adolescents and Young Adults with Colorectal Cancer.
    Salem ME, Battaglin F, Goldberg RM, Puccini A, et al · · 2020 · cited 40× · PMID 31848314 · DOI 10.1634/theoncologist.2019-0552
  8. Evidence-based medical oncology and interventional radiology paradigms for liver-dominant colorectal cancer metastases.
    Sag AA, Selcukbiricik F, Mandel NM. · · 2016 · cited 26× · PMID 27003990 · DOI 10.3748/wjg.v22.i11.3127

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