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NCT02921256

Veliparib, Pembrolizumab, and Combination Chemotherapy in Treating Patient With Locally Advanced Rectal Cancer

Completed Phase 2 Results posted Last updated 4 December 2025
What this trial tests

Phase 2 trial testing Capecitabine in Rectal Adenocarcinoma in 363 participants. Completed in 20 September 2023.

Timeline
11 January 2017
Primary endpoint
21 April 2020
20 September 2023

Quick facts

Lead sponsorNational Cancer Institute (NCI)
PhasePhase 2
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingnone
Primary purposetreatment
Enrollment363
Start date11 January 2017
Primary completion21 April 2020
Estimated completion20 September 2023
Sites650 locations across Puerto Rico, United States

Drugs / interventions tested

Conditions studied

Sponsor

National Cancer Institute (NCI)

Who can join

18 and older, any sex, with Rectal Adenocarcinoma or Stage II Rectal Cancer AJCC v7. 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.

Neoadjuvant Rectal Cancer (NAR) Score Primary · Baseline to up to 3 years

A linear regression model that controls for the stratification factors (cT-stage and cN-stage) will be used. Mean NAR scores along with standard errors and confidence intervals will be reported by treatment. The NAR score ranges from zero to 100 with lower values corresponding to better prognosis.

GroupValue95% CI
Arm Ia (mFOLFOX6, RT, Capecitabine)12.69.8 – 15.3
Arm II (mFOLFOX6, RT, Capecitabine, Veliparib)13.710.2 – 17.2
Arm Ib (mFOLFOX6, RT, Capecitabine)14.110.7 – 17.4
Arm III (mFOLFOX6, RT, Capecitabine, Pembrolizumab)11.58.5 – 14.5
Overall Survival Secondary · Time from randomization, assessed up to 3 years

Analyzed using the stratified log rank test with strata cT-stage and cN-stage. Kaplan-Meier plots will illustrate the distribution of these endpoints by treatment. Cox regression models will be used to estimate hazard ratios and associated confidence intervals.

GroupValue95% CI
Arm Ia (mFOLFOX6, RT, Capecitabine)0.9220.834 – 0.964
Arm II (mFOLFOX6, RT, Capecitabine, Veliparib)0.8490.754 – 0.910
Arm Ib (mFOLFOX6, RT, Capecitabine)0.8670.772 – 0.924
Arm III (mFOLFOX6, RT, Capecitabine, Pembrolizumab)0.9500.870 – 0.981
Disease Free Survival Secondary · Time from randomization, assessed up to 3 years

Analyzed using the stratified log rank test with strata cT-stage and cN-stage. Kaplan-Meier plots will illustrate the distribution of these endpoints by treatment. Cox regression models will be used to estimate hazard ratios and associated confidence intervals.

GroupValue95% CI
Arm Ia (mFOLFOX6, RT, Capecitabine)0.6750.559 – 0.766
Arm II (mFOLFOX6, RT, Capecitabine, Veliparib)0.6000.490 – 0.694
Arm Ib (mFOLFOX6, RT, Capecitabine)0.6380.528 – 0.729
Arm III (mFOLFOX6, RT, Capecitabine, Pembrolizumab)0.6360.522 – 0.730
Rate of Pathologic Complete Response (Nodes and Tumor) ypT0 and ypN0 Secondary · Up to 3 years

Pathologic Complete Response means no remaining cancer detectable in the pathology sample. Analyzed by a logistic regression model that controls for the stratification factors (cT-stage and cN-stage). Observed proportions along with confidence intervals will be presented by treatment.

GroupValue95% CI
Arm Ia (mFOLFOX6, RT, Capecitabine)21.612.9 – 32.7
Arm II (mFOLFOX6, RT, Capecitabine, Veliparib)33.823.0 – 46.0
Arm Ib (mFOLFOX6, RT, Capecitabine)29.419.0 – 41.7
Arm III (mFOLFOX6, RT, Capecitabine, Pembrolizumab)31.921.2 – 44.2
Rate of Sphincter Preservation Secondary · Up to 3 years

Sphincter preservation means that the surgical procedure used to remove the tumor did not disturb the sphincter muscle. Analyzed by a logistic regression model that controls for the stratification factors (cT-stage and cN-stage). Observed proportions along with confidence intervals will be presented by treatment.

GroupValue95% CI
Arm Ia (mFOLFOX6, RT, Capecitabine)52.541.0 – 63.8
Arm II (mFOLFOX6, RT, Capecitabine, Veliparib)59.347.8 – 70.1
Arm Ib (mFOLFOX6, RT, Capecitabine, Pembrolizumab)71.058.8 – 81.3
Arm III (mFOLFOX6, RT, Capecitabine, Pembrolizumab)59.446.9 – 71.1

Adverse events — posted to ClinicalTrials.gov

Time frame: Deaths were assessed for up to 3 years. Adverse Events were assessed from study entry to surgery, about 7 months.. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Arm Ia (mFOLFOX6, RT, Capecitabine)
Serious: 16/83 (19%)
Deaths: 7/87
Arm II (mFOLFOX6, RT, Capecitabine, Veliparib)
Serious: 25/88 (28%)
Deaths: 14/90
Arm Ib (mFOLFOX6, RT, Capecitabine)
Serious: 21/84 (25%)
Deaths: 13/93
Arm III (mFOLFOX6, RT, Capecitabine, Pembrolizumab)
Serious: 15/82 (18%)
Deaths: 6/87

Serious adverse events (81 terms)

ReactionSystemArm Ia (mFOLFOX6, RT, Cape…Arm II (mFOLFOX6, RT, Cape…Arm Ib (mFOLFOX6, RT, Cape…Arm III (mFOLFOX6, RT, Cap…
DiarrheaGastrointestinal disorders
HypokalemiaMetabolism and nutrition disorders
DehydrationMetabolism and nutrition disorders
Lung infectionInfections and infestations
Colonic obstructionGastrointestinal disorders
IleusGastrointestinal disorders
SepsisInfections and infestations
Thromboembolic eventVascular disorders
Abdominal painGastrointestinal disorders
EnterocolitisGastrointestinal disorders
Febrile neutropeniaBlood and lymphatic system disorders
HyperglycemiaMetabolism and nutrition disorders
HyponatremiaMetabolism and nutrition disorders
HypophosphatemiaMetabolism and nutrition disorders
Rectal painGastrointestinal disorders
SyncopeNervous system disorders
Urinary tract infectionInfections and infestations
VomitingGastrointestinal disorders
Enterocolitis infectiousInfections and infestations
Anorectal infectionInfections and infestations
Activated partial thromboplastin time prolongedInvestigations
Alanine aminotransferase increasedInvestigations
AnaphylaxisImmune system disorders
AnemiaBlood and lymphatic system disorders
AnorexiaMetabolism and nutrition disorders
Other adverse events (50 terms — click to expand)

ReactionSystemArm Ia (mFOLFOX6, RT, Cape…Arm II (mFOLFOX6, RT, Cape…Arm Ib (mFOLFOX6, RT, Cape…Arm III (mFOLFOX6, RT, Cap…
Neutrophil count decreasedInvestigations
FatigueGeneral disorders
DiarrheaGastrointestinal disorders
Lymphocyte count decreasedInvestigations
NauseaGastrointestinal disorders
White blood cell decreasedInvestigations
Peripheral sensory neuropathyNervous system disorders
AnorexiaMetabolism and nutrition disorders
HypertensionVascular disorders
Abdominal painGastrointestinal disorders
DehydrationMetabolism and nutrition disorders
Platelet count decreasedInvestigations
Anal painGastrointestinal disorders
AnemiaBlood and lymphatic system disorders
Dermatitis radiationInjury, poisoning and procedural complications
Rectal painGastrointestinal disorders
VomitingGastrointestinal disorders
ConstipationGastrointestinal disorders
HypokalemiaMetabolism and nutrition disorders
Mucositis oralGastrointestinal disorders
Weight lossInvestigations
Alanine aminotransferase increasedInvestigations
Thromboembolic eventVascular disorders
Infusion related reactionInjury, poisoning and procedural complications
HyperglycemiaMetabolism and nutrition disorders
HypothyroidismEndocrine disorders
AnxietyPsychiatric disorders
Aspartate aminotransferase increasedInvestigations
DyspneaRespiratory, thoracic and mediastinal disorders
HypoalbuminemiaMetabolism and nutrition disorders
ParesthesiaNervous system disorders
ProctitisGastrointestinal disorders
Rectal mucositisGastrointestinal disorders
ArthralgiaMusculoskeletal and connective tissue disorders
Back painMusculoskeletal and connective tissue disorders
DysgeusiaNervous system disorders
HypotensionVascular disorders
Urinary tract infectionInfections and infestations
HyperthyroidismEndocrine disorders
PainGeneral disorders

Most-reported serious reactions: Diarrhea, Hypokalemia, Dehydration, Lung infection, Colonic obstruction, Ileus, Sepsis, Thromboembolic event.

Data from ClinicalTrials.gov NCT02921256 adverse events section.

Sponsor's own description

This randomized phase II trial studies how well veliparib or pembrolizumab work with combination chemotherapy and radiation therapy in treating patients with rectal cancer that has spread from where it started to nearby tissue or lymph nodes (locally advanced). Veliparib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Drugs used in chemotherapy, such as modified (m)FOLFOX6 regimen, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Radiation therapy uses high-energy x-rays to kill tumor cells and shrink tumors. Giving veliparib or pembrolizumab with combination chemotherapy and radiation therapy may kill more tumor cells, make the tumor smaller, and reduce the amount of normal tissue that needs to be removed.

Publications & conference data

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

  1. Adoption of Total Neoadjuvant Therapy for Locally Advanced Rectal Cancer.
    Cercek A, Roxburgh CSD, Strombom P, Smith JJ, et al · · 2018 · cited 454× · PMID 29566109 · DOI 10.1001/jamaoncol.2018.0071
  2. Immunotherapy in colorectal cancer: current achievements and future perspective.
    Fan A, Wang B, Wang X, Nie Y, et al · · 2021 · cited 321× · PMID 34671202 · DOI 10.7150/ijbs.64077
  3. Use of Total Neoadjuvant Therapy for Locally Advanced Rectal Cancer: Initial Results From the Pembrolizumab Arm of a Phase 2 Randomized Clinical Trial.
    Rahma OE, Yothers G, Hong TS, Russell MM, et al · · 2021 · cited 158× · PMID 34196693 · DOI 10.1001/jamaoncol.2021.1683
  4. 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
  5. Radiation Treatment in Women with Ovarian Cancer: Past, Present, and Future.
    Fields EC, McGuire WP, Lin L, Temkin SM. · · 2017 · cited 57× · PMID 28871275 · DOI 10.3389/fonc.2017.00177
  6. Circulating Tumor DNA Predicts Pathologic and Clinical Outcomes Following Neoadjuvant Chemoradiation and Surgery for Patients With Locally Advanced Rectal Cancer.
    McDuff SGR, Hardiman KM, Ulintz PJ, Parikh AR, et al · · 2021 · cited 48× · PMID 34250394 · DOI 10.1200/po.20.00220
  7. Clinicopathological characteristics of high microsatellite instability/mismatch repair-deficient colorectal cancer: A narrative review.
    Mei WJ, Mi M, Qian J, Xiao N, et al · · 2022 · cited 41× · PMID 36618386 · DOI 10.3389/fimmu.2022.1019582
  8. 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

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Other trials of Capecitabine

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Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT02921256.

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