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NCT02393755

Nintedanib and Capecitabine in Treating Patients With Refractory Metastatic Colorectal Cancer

Completed Phase 1, PHASE2 Results posted Last updated 8 July 2021
What this trial tests

Phase 1, PHASE2 trial testing Capecitabine in Colon Adenocarcinoma in 42 participants. Completed in 18 May 2021.

Timeline
8 May 2015
Primary endpoint
1 November 2017
18 May 2021

Quick facts

Lead sponsorRoswell Park Cancer Institute
PhasePhase 1, PHASE2
StatusCompleted
Study typeINTERVENTIONAL
Allocationnon randomized
Designsingle group
Maskingnone
Primary purposetreatment
Enrollment42
Start date8 May 2015
Primary completion1 November 2017
Estimated completion18 May 2021
Sites2 locations across United States

Drugs / interventions tested

Conditions studied

Sponsor

Roswell Park Cancer Institute

Who can join

18 and older, any sex, with Colon Adenocarcinoma or Rectal Adenocarcinoma. 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.

To Examine the DLT Primary · At least 21 days.

The recommended Phase II dose is of the Nintedanib and Capecitabine combination is defined as the dose level that causes dose limiting toxicities (DLTs) in ≤ 1 out of 6 patients at highest dose level below the maximally administered dose. Capecitabine is fixed dose at 2000 mg/m2; while Nintedanib is evaluated at 150mg (dose level 1) and 200 mg (dose level 2).

GroupValue95% CI
Treatment (Capecitabine, Nintedanib)200
Progression Free Survival (PFS) Rate, Defined as the Proportion of Patients Who Survive Without Disease Progression Via the RECIST Version 1.1 (Phase II) Primary · At 18 weeks

Progressive disease is defined as at least a 20% increase in the sum of diameters of target lesions (the sum must also demonstrate an absolute increase of at least 5 mm) or the appearance of new lesions. Will be summarized using standard Kaplan-Meier methods.

GroupValue95% CI
Treatment (Capecitabine, Nintedanib)41.729.2 – 55.3
Median PFS (Phase II) Secondary · Up to 2 years

Progressive disease is defined as at least a 20% increase in the sum of diameters of target lesions (the sum must also demonstrate an absolute increase of at least 5 mm) or the appearance of new lesions. Estimates of median PFS will be obtained with corresponding 90% confidence intervals.

GroupValue95% CI
Treatment (Capecitabine, Nintedanib)3.42.1 – 4.2
Median OS (Phase II) Secondary · From the date of enrollment to the time of death, assessed up to 2 years

Overall survival is defined as time from date of subject enrollment to the date of death due to any cause. Estimates of median OS will be obtained with corresponding 90% confidence intervals.

GroupValue95% CI
Treatment (Capecitabine, Nintedanib)8.95.9 – 13.8
Objective Response Rate Secondary · After every 3 cycles (9 weeks) of therapy.

Overall Response is defined as Complete Response: Disappearance of all target lesions and any lymph nodes must have a reduction in short axis to \< 10 mm; or Partial Response: At least a 30% decrease in the sum of diameters of target lesions; or Stable Disease: Neither sufficient shrinkage to qualify for partial response, nor sufficient increase to qualify for progressive disease.

GroupValue95% CI
Treatment (Capecitabine, Nintedanib)58.344.7 – 70.8
Aggregate Rates of Adverse Events Measured by CTCAE Version 4.0 (Phase II) Secondary · Up to 30 days after the last dose of study drug

Number of Participants with Adverse Events, Graded According to the CTEP NCI Common Terminology Criteria for Adverse Events (CTCAE Version 4.0).

GroupValue95% CI
Treatment (Capecitabine, Nintedanib)3
Treatment (Capecitabine, Nintedanib)13
Treatment (Capecitabine, Nintedanib)16
Treatment (Capecitabine, Nintedanib)1

Adverse events — posted to ClinicalTrials.gov

Time frame: Day 1 of all Cycles, Cycle 1 Day 8 and Cycle 2 Day 8 (for phase 1 only), End of Treatment, an average of 102 days. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Dose Level 1: Capecitabine at 2000 mg/m2, Nintedanib at 150 mg
Serious: 0/3 (0%)
Deaths: 3/3
Dose Level 2: Capecitabine at 2000 mg/m2,Nintedanib at 200 mg
Serious: 10/39 (26%)
Deaths: 32/39

Serious adverse events (15 terms)

ReactionSystemDose Level 1: Capecitabine…Dose Level 2: Capecitabine…
Abdominal painGastrointestinal disorders
ConstipationGastrointestinal disorders
Intestinal perforationGastrointestinal disorders
Small intestinal obstructionGastrointestinal disorders
Hepatic failureHepatobiliary disorders
GastroenteritisInfections and infestations
SepsisInfections and infestations
Alanine aminotransferase increasedInvestigations
DehydrationMetabolism and nutrition disorders
Metastases to central nervous systemNeoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasm malignantNeoplasms benign, malignant and unspecified (incl cysts and polyps)
Mental status changesPsychiatric disorders
Urinary retentionRenal and urinary disorders
Pleural effusionRespiratory, thoracic and mediastinal disorders
Respiratory failureRespiratory, thoracic and mediastinal disorders
Other adverse events (150 terms — click to expand)

ReactionSystemDose Level 1: Capecitabine…Dose Level 2: Capecitabine…
NauseaGastrointestinal disorders
VomitingGastrointestinal disorders
FatigueGeneral disorders
DiarrhoeaGastrointestinal disorders
Aspartate aminotransferase increasedInvestigations
Alanine aminotransferase increasedInvestigations
Blood alkaline phosphatase increasedInvestigations
Decreased appetiteMetabolism and nutrition disorders
Palmar-plantar erythrodysaesthesia syndromeSkin and subcutaneous tissue disorders
AnaemiaBlood and lymphatic system disorders
ConstipationGastrointestinal disorders
HypoalbuminaemiaMetabolism and nutrition disorders
Abdominal painGastrointestinal disorders
Blood bilirubin increasedInvestigations
HyponatraemiaMetabolism and nutrition disorders
Neuropathy peripheralNervous system disorders
HypertensionVascular disorders
DizzinessNervous system disorders
HeadacheNervous system disorders
CoughRespiratory, thoracic and mediastinal disorders
DyspnoeaRespiratory, thoracic and mediastinal disorders
Dry skinSkin and subcutaneous tissue disorders
Weight decreasedInvestigations
PyrexiaGeneral disorders
LymphopeniaBlood and lymphatic system disorders
Abdominal distensionGastrointestinal disorders
StomatitisGastrointestinal disorders
White blood cell count decreasedInvestigations
HypokalaemiaMetabolism and nutrition disorders
Back painMusculoskeletal and connective tissue disorders
DehydrationMetabolism and nutrition disorders
ArthralgiaMusculoskeletal and connective tissue disorders
Taste disorderNervous system disorders
Pleural effusionRespiratory, thoracic and mediastinal disorders
Vision blurredEye disorders
Abdominal pain upperGastrointestinal disorders
Dry mouthGastrointestinal disorders
FlatulenceGastrointestinal disorders
ChillsGeneral disorders
HyperbilirubinaemiaHepatobiliary disorders

Most-reported serious reactions: Abdominal pain, Constipation, Intestinal perforation, Small intestinal obstruction, Hepatic failure, Gastroenteritis, Sepsis, Alanine aminotransferase increased.

Data from ClinicalTrials.gov NCT02393755 adverse events section.

Sponsor's own description

This phase I/II trial studies the side effects and best dose of nintedanib when given together with capecitabine and to see how well they work in treating patients with colorectal cancer that has not responded to previous treatment (refractory) and has spread to other places in the body (metastatic). Nintedanib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It may also block the growth of new blood vessels necessary for tumor growth. 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 nintedanib with capecitabine may be a better treatment for colorectal cancer.

Publications & conference data

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

  1. Profile of nintedanib in the treatment of solid tumors: the evidence to date.
    Awasthi N, Schwarz RE. · · 2015 · cited 53× · PMID 26677336 · DOI 10.2147/ott.s78805
  2. The role of tumor angiogenesis as a therapeutic target in colorectal cancer.
    Battaglin F, Puccini A, Intini R, Schirripa M, et al · · 2018 · cited 48× · PMID 29338550 · DOI 10.1080/14737140.2018.1428092
  3. The tyrosine kinase inhibitor nintedanib activates SHP-1 and induces apoptosis in triple-negative breast cancer cells.
    Liu CY, Huang TT, Chu PY, Huang CT, et al · · 2017 · cited 33× · PMID 28798401 · DOI 10.1038/emm.2017.114
  4. Emerging Systemic Therapies for Colorectal Cancer.
    Veenstra CM, Krauss JC. · · 2018 · cited 29× · PMID 29720904 · DOI 10.1055/s-0037-1602238
  5. Antiangiogenic therapy for refractory colorectal cancer: current options and future strategies.
    Riechelmann R, Grothey A. · · 2017 · cited 27× · PMID 28203302 · DOI 10.1177/1758834016676703
  6. Metastatic colorectal cancer: therapeutic options for treating refractory disease.
    Parmar A, Chan KKW, Ko YJ. · · 2019 · cited 13× · PMID 31819707 · DOI 10.3747/co.26.5575
  7. Plasticity and Functional Heterogeneity of Cancer-Associated Fibroblasts.
    Flynn JM, Thadani N, Gallagher EE, Azzaro I, et al · · 2025 · cited 10× · PMID 40729489 · DOI 10.1158/0008-5472.can-24-3037
  8. Protracted Inhibition of Vascular Endothelial Growth Factor Signaling Improves Survival in Metastatic Colorectal Cancer: A Systematic Review.
    Montagnani F, Di Leonardo G, Pino M, Perboni S, et al · · 2017 · cited 8× · PMID 28680835 · DOI 10.1515/jtim-2017-0005

Verify or expand the search:

Other trials of Capecitabine

Trials testing the same drug.

Other recruiting trials for Colon Adenocarcinoma

Currently open trials in the same condition.

Other Roswell Park Cancer Institute trials

Trials by the same sponsor.

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