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NCT03396926

Pembrolizumab, Capecitabine, and Bevacizumab for Treating Colorectal Cancer

Completed Phase 2 Results posted Last updated 28 February 2025
What this trial tests

Phase 2 trial testing Bevacizumab in Microsatellite Stable in 44 participants. Completed in 30 January 2024.

Timeline
18 April 2018
Primary endpoint
30 January 2024
30 January 2024

Quick facts

Lead sponsorUniversity of California, San Francisco
PhasePhase 2
StatusCompleted
Study typeINTERVENTIONAL
Allocationnon randomized
Designsequential
Maskingnone
Primary purposetreatment
Enrollment44
Start date18 April 2018
Primary completion30 January 2024
Estimated completion30 January 2024
Sites1 location across United States

Drugs / interventions tested

Conditions studied

Sponsor

University of California, San Francisco

Who can join

18 and older, any sex, with Microsatellite Stable or Mismatch Repair Protein Proficient. 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, Dose-limiting Toxicities (DLT) (Safety Lead-In Cohort) Primary · Up to 1 cycle (each cycle is 21 days)

A DLT evaluation of the first 6 participants will be conducted to confirm the safety of administering pembrolizumab at 200 mg (flat dosing) every three weeks with capecitabine and bevacizumab and include all participants in the safety lead in cohort who received at least 1 dose of study treatment. At least one laboratory or vital sign measurement obtained subsequent to at least one dose of study treatment is required for inclusion in the analysis including a baseline measure. Dose-limiting toxicity (DLT) must be clinically-significant toxicities which are at least possibly treatment-related pe

GroupValue95% CI
Safety Lead in Cohort: Treatment (Pembrolizumab, Bevacizumab, Capecitabine)0.33
Overall Response Rate (ORR) Primary · Up to 4 years

ORR is defined as the percentage of the participants in the ASaT population who have a confirmed complete response (CR) or a partial response (PR) (Overall Response (OR) = CR + PR) assessed by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 on Computerized Tomography (CT) or magnetic resonance imaging or (MRI) imaging if a CT cannot be obtained. The ORR and 95% confidence interval will be provided using exact binomial method proposed by Clopper and Pearson (1934).

GroupValue95% CI
ASaT Population (Pembrolizumab, Bevacizumab, Capecitabine)50.6 – 16.9
Disease Control Rate (DCR) Secondary · Up to 4 years

DCR is defined as the percentage of participants who have achieved confirmed CR or PR or have demonstrated stable disease (SD) for at least 24 weeks prior to any evidence of progression assessed by RECIST and immune-related RECIST (irRECIST). The percentage of participants and 95% confidence interval, will be provided using exact binomial method proposed by Clopper and Pearson (1934).

GroupValue95% CI
ASaT Population (Pembrolizumab, Bevacizumab, Capecitabine)2516.7 – 41.2
Median Duration of Response (DOR) Secondary · Up to 4 years

Duration of response is defined as the time from first documented evidence of CR or PR assessed by RECIST and irRECIST until disease progression or death due to any cause, whichever occurs first. Kaplan-Meier (KM) curves and median estimates from will be reported

GroupValue95% CI
ASaT Population (Pembrolizumab, Bevacizumab, Capecitabine)13.512.3 – NA
Median Overall Survival (OS) Secondary · Up to 4 years

OS is defined as the time from first day of study treatment to death due to any cause. Subjects without documented death at the time of the final analysis will be censored at the date of the last follow-up. KM curves and median estimates from the KM curves will be provided as appropriate.

GroupValue95% CI
ASaT Population (Pembrolizumab, Bevacizumab, Capecitabine)10.18.52 – 15.2
Median Progression-Free Survival (PFS) Secondary · Up to 4 years

PFS is defined as the time from first day of study treatment to the first documented disease progression or death due to any cause, whichever occurs first. Median estimates in months and the 95% confidence interval will be reported.

GroupValue95% CI
ASaT Population (Pembrolizumab, Bevacizumab, Capecitabine)4.293.68 – 6.05

Adverse events — posted to ClinicalTrials.gov

Time frame: Up to 4 years. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Safety Lead in Cohort: Treatment (Pembrolizumab, Bevacizumab, Capecitabine)
Serious: 4/7 (57%)
Deaths: 0/7
Expansion Cohort: Treatment (Pembrolizumab, Bevacizumab, Capecitabine)
Serious: 11/37 (30%)
Deaths: 1/37

Serious adverse events (26 terms)

ReactionSystemSafety Lead in Cohort: Tre…Expansion Cohort: Treatmen…
Abdominal painGastrointestinal disorders
FeverGeneral disorders
Acute kidney injuryRenal and urinary disorders
Blood bilirubin increasedInvestigations
ColitisGastrointestinal disorders
Colonic obstructionGastrointestinal disorders
Colonic perforationGastrointestinal disorders
Duodenal perforationGastrointestinal disorders
Duodenal obstructionGastrointestinal disorders
DyspneaRespiratory, thoracic and mediastinal disorders
EnterocolitisGastrointestinal disorders
FatigueGeneral disorders
Gastrointestinal disorders - Other, specifyGastrointestinal disorders
General disorders and administration site conditions - Other, specifyGeneral disorders
Hepatobiliary disorders - Other, specifyHepatobiliary disorders
HypotensionVascular disorders
Immune system disorders - Other, specifyImmune system disorders
Lung InfectionInfections and infestations
LeukocytosisBlood and lymphatic system disorders
Mucositis oralGastrointestinal disorders
PancreatitisGastrointestinal disorders
Respiratory failureRespiratory, thoracic and mediastinal disorders
Small intestinal obstructionGastrointestinal disorders
Thromboembolic eventVascular disorders
Urinary tract painRenal and urinary disorders
Other adverse events (156 terms — click to expand)

ReactionSystemSafety Lead in Cohort: Tre…Expansion Cohort: Treatmen…
FatigueGeneral disorders
Palmar-plantar erythrodysesthesia syndromeSkin and subcutaneous tissue disorders
Abdominal painGastrointestinal disorders
ConstipationGastrointestinal disorders
Blood bilirubin increasedInvestigations
NauseaGastrointestinal disorders
AnorexiaMetabolism and nutrition disorders
DiarrheaGastrointestinal disorders
Mucositis oralGastrointestinal disorders
VomitingGastrointestinal disorders
Dry skinSkin and subcutaneous tissue disorders
Skin hyperpigmentationSkin and subcutaneous tissue disorders
Weight lossInvestigations
Back painMusculoskeletal and connective tissue disorders
Non-cardiac chest painGeneral disorders
Rash maculo-papularSkin and subcutaneous tissue disorders
ProteinuriaRenal and urinary disorders
Aspartate aminotransferase increasedInvestigations
Platelet count decreasedInvestigations
ArthralgiaMusculoskeletal and connective tissue disorders
DyspneaRespiratory, thoracic and mediastinal disorders
CoughRespiratory, thoracic and mediastinal disorders
AnemiaBlood and lymphatic system disorders
Skin and subcutaneous tissue disorders - Other, specifySkin and subcutaneous tissue disorders
Pain in extremityMusculoskeletal and connective tissue disorders
HypoalbuminemiaMetabolism and nutrition disorders
Gastrointestinal disorders - Other, specifyGastrointestinal disorders
FeverGeneral disorders
Edema limbsGeneral disorders
HeadacheNervous system disorders
HypertensionVascular disorders
Fecal incontinenceGastrointestinal disorders
Abdominal distensionGastrointestinal disorders
General disorders and administration site conditions - Other, specifyGeneral disorders
ChillsGeneral disorders
EpistaxisRespiratory, thoracic and mediastinal disorders
WheezingRespiratory, thoracic and mediastinal disorders
HyponatremiaMetabolism and nutrition disorders
Upper respiratory infectionInfections and infestations
Oral painGastrointestinal disorders

Most-reported serious reactions: Abdominal pain, Fever, Acute kidney injury, Blood bilirubin increased, Colitis, Colonic obstruction, Colonic perforation, Duodenal perforation.

Data from ClinicalTrials.gov NCT03396926 adverse events section.

Sponsor's own description

This phase II trial studies the side effects and best dose of capecitabine when given together with pembrolizumab and bevacizumab, and investigates how well they work in treating patients with microsatellite stable colorectal cancer that has spread to nearby tissues or lymph nodes, has spread to other places in the body, or that cannot be removed by surgery. Monoclonal antibodies, such as pembrolizumab and bevacizumab, may interfere with the ability of tumor cells to grow and spread. Drugs used in chemotherapy, such as capecitabine, 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. Giving capecitabine together with pembrolizumab and bevacizumab may work better in treating patients with colorectal cancer.

Publications & conference data

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

  1. Advances in immunotherapy for colorectal cancer: a review.
    Golshani G, Zhang Y. · · 2020 · cited 170× · PMID 32536977 · DOI 10.1177/1756284820917527
  2. Review of PD-1/PD-L1 Inhibitors in Metastatic dMMR/MSI-H Colorectal Cancer.
    Oliveira AF, Bretes L, Furtado I. · · 2019 · cited 152× · PMID 31139574 · DOI 10.3389/fonc.2019.00396
  3. PD-1 and PD-L1 inhibitors in cold colorectal cancer: challenges and strategies.
    Lin KX, Istl AC, Quan D, Skaro A, et al · · 2023 · cited 90× · PMID 37831146 · DOI 10.1007/s00262-023-03520-5
  4. Immunotherapy with immune checkpoint inhibitors in colorectal cancer: what is the future beyond deficient mismatch-repair tumours?
    Huyghe N, Baldin P, Van den Eynde M. · · 2020 · cited 79× · PMID 32104582 · DOI 10.1093/gastro/goz061
  5. Improving antitumor immunity using antiangiogenic agents: Mechanistic insights, current progress, and clinical challenges.
    Li SJ, Chen JX, Sun ZJ. · · 2021 · cited 63× · PMID 34137513 · DOI 10.1002/cac2.12183
  6. Mechanism and strategies of immunotherapy resistance in colorectal cancer.
    Shan J, Han D, Shen C, Lei Q, et al · · 2022 · cited 54× · PMID 36238278 · DOI 10.3389/fimmu.2022.1016646
  7. Recent developments in immunotherapy for gastrointestinal tract cancers.
    Chong X, Madeti Y, Cai J, Li W, et al · · 2024 · cited 52× · PMID 39123202 · DOI 10.1186/s13045-024-01578-x
  8. Navigating tumor angiogenesis: therapeutic perspectives and myeloid cell regulation mechanism.
    Yang F, Lee G, Fan Y. · · 2024 · cited 45× · PMID 38580870 · DOI 10.1007/s10456-024-09913-z

Verify or expand the search:

Other trials of Bevacizumab

Trials testing the same drug.

Other recruiting trials for Microsatellite Stable

Currently open trials in the same condition.

Other University of California, San Francisco trials

Trials by the same sponsor.

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