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NCT03844750

Preoperative Immunotherapy (Pembrolizumab) for Patients With Colorectal Cancer and Resectable Hepatic Metastases

Terminated Phase 2 Results posted Last updated 31 December 2025
What this trial tests

Phase 2 trial testing Hepatectomy in Metastatic Malignant Neoplasm in the Liver in 6 participants. Terminated before completion.

Timeline
22 July 2019
Primary endpoint
30 September 2025
30 September 2025

Quick facts

Lead sponsorChloe Atreya, MD, PhD
PhasePhase 2
StatusTerminated
Study typeINTERVENTIONAL
Allocationna
Designsingle group
Maskingnone
Primary purposetreatment
Enrollment6
Start date22 July 2019
Primary completion30 September 2025
Estimated completion30 September 2025
Sites1 location across United States

Drugs / interventions tested

Conditions studied

Sponsor

Chloe Atreya, MD, PhD

Who can join

18 and older, any sex, with Metastatic Malignant Neoplasm in the Liver or Stage IV Colorectal Cancer AJCC v8. 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.

Proportion of Participants With Treatment-related, Adverse Events Secondary · Up to 2 years

Adverse events (AEs) will be analyzed including but not limited to all AEs, serious (S)AEs, and fatal AEs using NCI Common Terminology Criteria for Adverse Events (CTCAE) version 5 for classification. Due to the potential for late toxicities from pembrolizumab, patients will be followed for 1 year after their last dose of pembrolizumab.

GroupValue95% CI
Treatment (vactosertib, pembrolizumab, surgery)1.00
Proportion of Participants With Events of Clinical Interest (ECIs) Secondary · Up to 2 years

Specific immune-related AEs (irAEs) will be collected and designated as immune-related events of clinical interest (ECIs). The study will use descriptive statistics to report on the safety/toxicity. Due to the potential for late toxicities from pembrolizumab, patients will be followed for 1 year after their last dose of pembrolizumab

GroupValue95% CI
Treatment (vactosertib, pembrolizumab, surgery)0.33
Proportion of Participants With Perioperative Complications Secondary · Up to 1 month

The proportion of participants with reported perioperative complications related to study treatment will be reported.

GroupValue95% CI
Treatment (vactosertib, pembrolizumab, surgery)0.17
Proportion of Participants With an R0 Resection Secondary · Up to 1 month

Participants who undergo surgical resection of liver metastases will be evaluable and the proportion of participants requiring an R0 resection will be reported

GroupValue95% CI
Treatment (vactosertib, pembrolizumab, surgery)0.83
Proportion of Participants With a Pathologic Response Secondary · Up to 1 year

Participants who undergo surgical resection of liver metastases will be evaluable and the proportion of participants with a pathological tumor response will be reported

GroupValue95% CI
Treatment (vactosertib, pembrolizumab, surgery)0
Median Relapse-free Survival (RFS) Secondary · Up to 2 years from day of surgery

The time from objective response defined as radiographic evidence of relapse on surveillance CT scans after surgery to progression or death, whichever occurs first, will be used to determine relapse-free survival for participants who received adjuvant vactosertib and pembrolizumab.

GroupValue95% CI
Treatment (vactosertib, pembrolizumab, surgery)14.514.44 – NA

Adverse events — posted to ClinicalTrials.gov

Time frame: Up to 2 years. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Treatment (Vactosertib, Pembrolizumab, Surgery)
Serious: 1/6 (17%)
Deaths: 0/6

Serious adverse events (1 terms)

ReactionSystemTreatment (Vactosertib, Pe…
ColitisGastrointestinal disorders
Other adverse events (27 terms — click to expand)

ReactionSystemTreatment (Vactosertib, Pe…
FatigueGeneral disorders
HeadacheNervous system disorders
Rash maculo-papularSkin and subcutaneous tissue disorders
HypothyroidismEndocrine disorders
Abdominal distensionGastrointestinal disorders
NauseaGastrointestinal disorders
HypercalcemiaMetabolism and nutrition disorders
Pain in extremityMusculoskeletal and connective tissue disorders
Peripheral sensory neuropathyNervous system disorders
Acute kidney injuryRenal and urinary disorders
CoughRespiratory, thoracic and mediastinal disorders
HyperhidrosisSkin and subcutaneous tissue disorders
AnemiaBlood and lymphatic system disorders
HyperthyroidismEndocrine disorders
Abdominal painGastrointestinal disorders
ColitisGastrointestinal disorders
DiarrheaGastrointestinal disorders
Edema limbsGeneral disorders
PainGeneral disorders
Neutrophil count decreasedInvestigations
Platelet count decreasedInvestigations
AnorexiaMetabolism and nutrition disorders
Back PainMusculoskeletal and connective tissue disorders
PruritusSkin and subcutaneous tissue disorders
Rash acneiformSkin and subcutaneous tissue disorders
Skin and subcutaneous tissue disorders, OtherSkin and subcutaneous tissue disorders
Thromboembolic eventVascular disorders

Most-reported serious reactions: Colitis.

Data from ClinicalTrials.gov NCT03844750 adverse events section.

Sponsor's own description

This phase II trials studies how well pembrolizumab and vactosertib work after standard of care chemotherapy in patients with colorectal cancer that has spread to the liver that can be removed by surgery (resectable hepatic metastases). 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. Vactosertib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving pembrolizumab and vactosertib after standard of care chemotherapy, but before liver metastases surgery, may help shrink the cancer prior to surgery. This study also investigates pembrolizumab and vactosertib after liver metastases surgery, decrease the risk of the cancer recurring (coming back).

Publications & conference data

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

  1. Trial watch: chemotherapy-induced immunogenic cell death in immuno-oncology.
    Vanmeerbeek I, Sprooten J, De Ruysscher D, Tejpar S, et al · · 2020 · cited 179× · PMID 32002302 · DOI 10.1080/2162402x.2019.1703449
  2. TGF-beta signal transduction: biology, function and therapy for diseases.
    Tie Y, Tang F, Peng D, Zhang Y, et al · · 2022 · cited 97× · PMID 36534225 · DOI 10.1186/s43556-022-00109-9
  3. The Liver-Immunity Nexus and Cancer Immunotherapy.
    Lee JC, Green MD, Huppert LA, Chow C, et al · · 2022 · cited 87× · PMID 34285059 · DOI 10.1158/1078-0432.ccr-21-1193
  4. The difficulty in translating the preclinical success of combined TGFβ and immune checkpoint inhibition to clinical trial.
    Metropulos AE, Munshi HG, Principe DR. · · 2022 · cited 59× · PMID 36455409 · DOI 10.1016/j.ebiom.2022.104380
  5. Development of pharmacological immunoregulatory anti-cancer therapeutics: current mechanistic studies and clinical opportunities.
    Yin N, Li X, Zhang X, Xue S, et al · · 2024 · cited 48× · PMID 38773064 · DOI 10.1038/s41392-024-01826-z
  6. Advances and Challenges in Targeting TGF-β Isoforms for Therapeutic Intervention of Cancer: A Mechanism-Based Perspective.
    Danielpour D. · · 2024 · cited 38× · PMID 38675493 · DOI 10.3390/ph17040533
  7. Biomarkers of Response and Resistance to Immunotherapy in Microsatellite Stable Colorectal Cancer: Toward a New Personalized Medicine.
    Huyghe N, Benidovskaya E, Stevens P, Van den Eynde M. · · 2022 · cited 36× · PMID 35565369 · DOI 10.3390/cancers14092241
  8. The Love-Hate Relationship Between TGF-β Signaling and the Immune System During Development and Tumorigenesis.
    Chen B, Mu C, Zhang Z, He X, et al · · 2022 · cited 35× · PMID 35720407 · DOI 10.3389/fimmu.2022.891268

Verify or expand the search:

Other trials of Hepatectomy

Trials testing the same drug.

Other recruiting trials for Metastatic Malignant Neoplasm in the Liver

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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/NCT03844750.

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