Nintedanib and Capecitabine in Treating Patients With Refractory Metastatic Colorectal Cancer

Sponsor
Roswell Park Cancer Institute (Other)
Overall Status
Completed
CT.gov ID
NCT02393755
Collaborator
National Cancer Institute (NCI) (NIH), Boehringer Ingelheim (Industry), National Comprehensive Cancer Network (Other)
42
2
2
72.3
21
0.3

Study Details

Study Description

Brief Summary

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.

Detailed Description

PRIMARY OBJECTIVES:
    1. To estimate the maximum tolerated dose (MTD) and examine the dose-limiting toxicities of nintedanib when administered with capecitabine within the study population and, establish the recommended phase II dose (RP2D). (Phase I)
    1. To assess progression free survival at 18 weeks. (Phase II)
SECONDARY OBJECTIVES:
    1. To assess median progression free survival. (Phase II)
    1. To assess median overall survival from the date of enrollment to the time of death will be documented. (Phase II)
    1. To assess the objective response rate as measured by Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1. (Phase II)
    1. To assess the toxicity of dose regimen using the Cancer Therapy Evaluation Program (CTEP) National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE version 4.0). (Phase II)
TERTIARY OBJECTIVES:
    1. Measurement of circulating angiogenic cytokines (CAFs): vascular endothelial growth factor (VEGF), soluble vascular endothelial growth factor receptor (sVEGFR) 1/2, placental growth factor (PlGF), granulocyte macrophage colony-stimulating factor (GMCSF), leptin, interleukin (IL)-1 alpha (a), IL-8, IL-6, fibroblast growth factor basic (FGFb), osteopontin and pentraxin-3. (Phase II)
    1. Measurement of drug levels and pharmacokinetic (PK)/pharmacodynamic (PD) modeling. (Phase II)

OUTLINE: This is a phase I, dose-escalation study of nintedanib followed by a phase II study.

Patients receive capecitabine orally (PO) twice daily (BID) (every 12 hours) on days 1-14 and nintedanib PO BID (every 12 hours) on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days, every 28 days until resolution or satisfactory stabilization of persistent drug-related toxicity, and then every 6 months thereafter.

Study Design

Study Type:
Interventional
Actual Enrollment :
42 participants
Allocation:
Non-Randomized
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase I/II Study of Nintedanib and Capecitabine in Refractory Metastatic Colorectal Cancer
Actual Study Start Date :
May 8, 2015
Actual Primary Completion Date :
Nov 1, 2017
Actual Study Completion Date :
May 18, 2021

Arms and Interventions

Arm Intervention/Treatment
Experimental: Treatment (capecitabine, nintedanib)

Patients received capecitabine PO BID (every 12 hours) on days 1-14 and nintedanib PO BID (every 12 hours) on days 1-21. Courses repeated every 21 days in the absence of disease progression or unacceptable toxicity.

Drug: Capecitabine
Given PO
Other Names:
  • Ro 09-1978/000
  • Xeloda
  • Other: Laboratory Biomarker Analysis
    Correlative studies

    Drug: Nintedanib
    Given PO
    Other Names:
  • BIBF 1120
  • BIBF-1120
  • Intedanib
  • Multitargeted Tyrosine Kinase Inhibitor BIBF 1120
  • tyrosine kinase inhibitor BIBF 1120
  • Vargatef
  • Other: Pharmacological Study
    Correlative studies

    Experimental: Treatment (capecitabine , nintendanib)

    Patients receive the highest safe dose of the combination of nintedanib and capcitabine.

    Drug: Nintedanib
    Given PO
    Other Names:
  • BIBF 1120
  • BIBF-1120
  • Intedanib
  • Multitargeted Tyrosine Kinase Inhibitor BIBF 1120
  • tyrosine kinase inhibitor BIBF 1120
  • Vargatef
  • Outcome Measures

    Primary Outcome Measures

    1. To Examine the DLT [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).

    2. Progression Free Survival (PFS) Rate, Defined as the Proportion of Patients Who Survive Without Disease Progression Via the RECIST Version 1.1 (Phase II) [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.

    Secondary Outcome Measures

    1. Median PFS (Phase II) [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.

    2. Median OS (Phase II) [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.

    3. Objective Response Rate [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.

    4. Aggregate Rates of Adverse Events Measured by CTCAE Version 4.0 (Phase II) [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).

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    • Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1

    • Hemoglobin >= 9 g/dL

    • Absolute neutrophil count >= 1500/mm^3

    • Platelet count >= 100,000/mm^3

    • Creatinine =< 1.5 upper limit of normal (ULN) AND creatinine clearance (CrCl) > 50 mL/min by Cockcroft-Gault equation

    • Males = (140 -age (yrs) (body weight (kg)/(72) (serum creatinine) (mg/dL)

    • Females = 0.85 * (140-age (yrs) (body weight (kg)/(72)(serum creatinine (mg/dL)

    • Bilirubin < ULN

    • Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 1.5 ULN if without liver metastases

    • AST/ALT =< 2.5 x ULN if with liver metastases

    • Coagulation parameters: international normalized ratio (INR) =< 2, prothrombin time (PT) and partial thromboplastin time (PTT) < 1.5 X institutional ULN

    • Have measurable disease per RECIST 1.1 criteria

    • Histologically or cytologically proven adenocarcinoma of the colon or rectum

    • Prior progression following a fluoropyrimidine-based therapy and progression following or intolerance to irinotecan and oxaliplatin, as well as anti-epidermal growth factor receptor (EGFR) therapy (e.g., panitumumab or cetuximab) for rat sarcoma viral oncogene homolog (RAS) wild-type patients

    • Ability to swallow and retain oral medication

    • Participants of child-bearing potential must agree to use adequate contraceptive methods (e.g., hormonal or barrier method of birth control; abstinence) prior to study entry and for three months following completion of therapy; should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately

    • Participant or legal representative must understand the investigational nature of this study and sign an Independent Ethics Committee/Institutional Review Board approved written informed consent form prior to receiving any study related procedure

    Exclusion Criteria:
    • Prior treatment with nintedanib

    • Prior treatment with regorafenib

    • Major injuries or surgery within the 4 weeks prior to initiation of therapy with incomplete wound healing or planned surgery during the on-study treatment period

    • Uncontrolled hypertension: systolic blood pressure >= 160, diastolic blood pressure >= 90

    • Urine protein/creatinine ratio >= 1.0

    • History of clinically significant hemorrhagic or thrombotic event within the past 6 months, not including uncomplicated catheter-associated venous thrombosis; patients on anti-coagulation are not permitted to be on any oral formulations (warfarin, rivaroxaban, dabigatran, etc.) due to concern for drug-drug interaction

    • Unstable angina, symptomatic congestive heart failure or cardiac arrhythmia requiring anti-arrhythmic therapy (beta-blockers, calcium channel blockers and digoxin are allowed)

    • History of cerebrovascular or myocardial ischemia within 6 months of initiation

    • Known inherited predisposition to bleeding or thrombosis

    • Known active or chronic hepatitis B or C or human immunodeficiency virus (HIV)

    • Untreated brain metastases

    • History of second primary malignancy diagnosed within 3 years prior to enrollment, excluding:

    • In-situ cervical carcinoma

    • Superficial bladder cancer

    • Non-melanoma skin cancer

    • Stage I breast cancer

    • Low grade (Gleason =< 6) localized prostate cancer

    • Any additional malignancy which has been in clinical remission for at least 1 year

    • Pregnant or nursing female participants

    • Unwilling or unable to follow protocol requirements

    • Any condition which in the Investigator's opinion deems the participant an unsuitable candidate to receive study drug

    • Received an investigational agent within 4 weeks prior to enrollment

    • PHASE I: History of intolerance to capecitabine at doses =< 1000 mg/m^2 BID, as defined by documented >= grade 3 hand-foot syndrome, documented severe diarrhea requiring hospitalization, or other documented severe adverse events (AEs) attributable to capecitabine

    • PHASE II: History of intolerance to capecitabine at doses below 1000 mg/m^2 BID, as defined by documented >= grade 3 hand-foot syndrome; documented severe diarrhea requiring hospitalization; or other documented severe AEs attributable to capecitabine

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 City of Hope Comprehensive Cancer Center Duarte California United States 91010
    2 Roswell Park Cancer Institute Buffalo New York United States 14263

    Sponsors and Collaborators

    • Roswell Park Cancer Institute
    • National Cancer Institute (NCI)
    • Boehringer Ingelheim
    • National Comprehensive Cancer Network

    Investigators

    • Principal Investigator: Christos Fountzilas, Roswell Park Cancer Institute

    Study Documents (Full-Text)

    More Information

    Publications

    None provided.
    Responsible Party:
    Roswell Park Cancer Institute
    ClinicalTrials.gov Identifier:
    NCT02393755
    Other Study ID Numbers:
    • I 265514
    • NCI-2015-00223
    • I 265514
    • P30CA016056
    First Posted:
    Mar 19, 2015
    Last Update Posted:
    Jul 8, 2021
    Last Verified:
    Jul 1, 2021

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group Title Dose Level 1: Capecitabine at 2000 mg/2, Nintedanib at 150 mg Dose Level 2: Capecitabine at 2000 mg/m2, Nintedanib at 200 mg
    Arm/Group Description Dose Level (Arm) 1: Capecitabine at 2000 mg/m2 PO daily and Nintedanib at 150 mg PO bid Capecitabine at 2000 mg/m2 will be administration will be twice daily for two weeks (the first 2 weeks of each 21 day cycle), followed by a 1 week rest. Nintedanib 150 mg will be administered twice daily for 21 days (i.e., 1 complete 3-week cycle). Both capecitabine and nintedanib may be taken together, with water, within 30 minutes following a meal. Doses should be separated by approximately 12 hours, with the PM dose being 12 hours (+/- 2 hours) after the AM dose. Dose Level (Arm) 2: Capecitabine at 2000 mg/m2 PO daily and Nintedanib at 200 mg PO bid Capecitabine at 2000 mg/m2 will be administration will be twice daily for two weeks (the first 2 weeks of each 21 day cycle), followed by a 1 week rest. Nintedanib 2000 mg will be administered twice daily for 21 days (i.e., 1 complete 3-week cycle). Both capecitabine and nintedanib may be taken together, with water, within 30 minutes following a meal. Doses should be separated by approximately 12 hours, with the PM dose being 12 hours (+/- 2 hours) after the AM dose.
    Period Title: Overall Study
    STARTED 3 39
    COMPLETED 3 32
    NOT COMPLETED 0 7

    Baseline Characteristics

    Arm/Group Title Dose Level 1: Capecitabine at 2000 mg/m2, Nintedanib at 150 mg Dose Level 2: Capecitabine at 2000 mg/m2,Nintedanib at 200 mg Total
    Arm/Group Description Dose Level (Arm) 1: Capecitabine at 2000 mg/m2 PO daily and Nintedanib at 150 mg PO bid Capecitabine at 2000 mg/m2 will be administration will be twice daily for two weeks (the first 2 weeks of each 21 day cycle), followed by a 1 week rest. Nintedanib 150 mg will be administered twice daily for 21 days (i.e., 1 complete 3-week cycle). Both capecitabine and nintedanib may be taken together, with water, within 30 minutes following a meal. Doses should be separated by approximately 12 hours, with the PM dose being 12 hours (+/- 2 hours) after the AM dose. Dose Level (Arm) 2: Capecitabine at 2000 mg/m2 PO daily and Nintedanib at 200 mg PO bid Capecitabine at 2000 mg/m2 will be administration will be twice daily for two weeks (the first 2 weeks of each 21 day cycle), followed by a 1 week rest. Nintedanib 2000 mg will be administered twice daily for 21 days (i.e., 1 complete 3-week cycle). Both capecitabine and nintedanib may be taken together, with water, within 30 minutes following a meal. Doses should be separated by approximately 12 hours, with the PM dose being 12 hours (+/- 2 hours) after the AM dose. Total of all reporting groups
    Overall Participants 3 39 42
    Age (years) [Mean (Full Range) ]
    Mean (Full Range) [years]
    61.0
    57.3
    57.6
    Sex: Female, Male (Count of Participants)
    Female
    2
    66.7%
    22
    56.4%
    24
    57.1%
    Male
    1
    33.3%
    17
    43.6%
    18
    42.9%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    0
    0%
    0
    0%
    0
    0%
    Asian
    0
    0%
    5
    12.8%
    5
    11.9%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    0
    0%
    0
    0%
    Black or African American
    0
    0%
    1
    2.6%
    1
    2.4%
    White
    3
    100%
    30
    76.9%
    33
    78.6%
    More than one race
    0
    0%
    0
    0%
    0
    0%
    Unknown or Not Reported
    0
    0%
    3
    7.7%
    3
    7.1%
    ECOG Status at Baseline (Count of Participants)
    Grade 0
    2
    66.7%
    21
    53.8%
    23
    54.8%
    Grade 1
    1
    33.3%
    18
    46.2%
    19
    45.2%
    Body Weight (Kilograms (kg)) [Mean (Full Range) ]
    Mean (Full Range) [Kilograms (kg)]
    69.2
    77.8
    77.2
    Presence of liver metastasis (Count of Participants)
    Count of Participants [Participants]
    3
    100%
    20
    51.3%
    23
    54.8%

    Outcome Measures

    1. Primary Outcome
    Title To Examine the DLT
    Description 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).
    Time Frame At least 21 days.

    Outcome Measure Data

    Analysis Population Description
    Patients who were evaluable for DLTs
    Arm/Group Title Treatment (Capecitabine, Nintedanib)
    Arm/Group Description Patients receive capecitabine PO BID (every 12 hours) on days 1-14 and nintedanib PO BID (every 12 hours) on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Capecitabine: Given PO Laboratory Biomarker Analysis: Correlative studies Nintedanib: Given PO Pharmacological Study: Correlative studies
    Measure Participants 9
    Number [mg]
    200
    2. Primary Outcome
    Title Progression Free Survival (PFS) Rate, Defined as the Proportion of Patients Who Survive Without Disease Progression Via the RECIST Version 1.1 (Phase II)
    Description 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.
    Time Frame At 18 weeks

    Outcome Measure Data

    Analysis Population Description
    All treated and eligible patients at dose level 2
    Arm/Group Title Treatment (Capecitabine, Nintedanib)
    Arm/Group Description Patients receive capecitabine PO BID (every 12 hours) on days 1-14 and nintedanib PO BID (every 12 hours) on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Capecitabine: Given PO Laboratory Biomarker Analysis: Correlative studies Nintedanib: Given PO Pharmacological Study: Correlative studies
    Measure Participants 36
    Number (90% Confidence Interval) [percentage of participants]
    41.7
    1390%
    3. Secondary Outcome
    Title Median PFS (Phase II)
    Description 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.
    Time Frame Up to 2 years

    Outcome Measure Data

    Analysis Population Description
    All treated and eligible patients at dose level 2
    Arm/Group Title Treatment (Capecitabine, Nintedanib)
    Arm/Group Description Patients receive capecitabine PO BID (every 12 hours) on days 1-14 and nintedanib PO BID (every 12 hours) on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Capecitabine: Given PO Laboratory Biomarker Analysis: Correlative studies Nintedanib: Given PO Pharmacological Study: Correlative studies
    Measure Participants 36
    Median (90% Confidence Interval) [months]
    3.4
    4. Secondary Outcome
    Title Median OS (Phase II)
    Description 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.
    Time Frame From the date of enrollment to the time of death, assessed up to 2 years

    Outcome Measure Data

    Analysis Population Description
    All treated and eligible patients at dose level 2
    Arm/Group Title Treatment (Capecitabine, Nintedanib)
    Arm/Group Description Patients receive capecitabine PO BID (every 12 hours) on days 1-14 and nintedanib PO BID (every 12 hours) on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Capecitabine: Given PO Laboratory Biomarker Analysis: Correlative studies Nintedanib: Given PO Pharmacological Study: Correlative studies
    Measure Participants 36
    Median (90% Confidence Interval) [months]
    8.9
    5. Secondary Outcome
    Title Objective Response Rate
    Description 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.
    Time Frame After every 3 cycles (9 weeks) of therapy.

    Outcome Measure Data

    Analysis Population Description
    All treated and eligible patients at dose level 2
    Arm/Group Title Treatment (Capecitabine, Nintedanib)
    Arm/Group Description Patients receive capecitabine PO BID (every 12 hours) on days 1-14 and nintedanib PO BID (every 12 hours) on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Capecitabine: Given PO Laboratory Biomarker Analysis: Correlative studies Nintedanib: Given PO Pharmacological Study: Correlative studies
    Measure Participants 36
    Number (90% Confidence Interval) [percentage of participants]
    58.3
    1943.3%
    6. Secondary Outcome
    Title Aggregate Rates of Adverse Events Measured by CTCAE Version 4.0 (Phase II)
    Description Number of Participants with Adverse Events, Graded According to the CTEP NCI Common Terminology Criteria for Adverse Events (CTCAE Version 4.0).
    Time Frame Up to 30 days after the last dose of study drug

    Outcome Measure Data

    Analysis Population Description
    All treated and eligible patients at dose level 2
    Arm/Group Title Treatment (Capecitabine, Nintedanib)
    Arm/Group Description Patients receive capecitabine PO BID (every 12 hours) on days 1-14 and nintedanib PO BID (every 12 hours) on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Capecitabine: Given PO Laboratory Biomarker Analysis: Correlative studies Nintedanib: Given PO Pharmacological Study: Correlative studies
    Measure Participants 36
    Grade 1
    3
    100%
    Grade 2
    13
    433.3%
    Grade 3
    16
    533.3%
    Grade 4
    1
    33.3%
    Grade 5
    3
    100%

    Adverse Events

    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
    Adverse Event Reporting Description All treated and eligible patients
    Arm/Group Title Dose Level 1: Capecitabine at 2000 mg/m2, Nintedanib at 150 mg Dose Level 2: Capecitabine at 2000 mg/m2,Nintedanib at 200 mg
    Arm/Group Description Dose Level (Arm) 1: Capecitabine at 2000 mg/m2 PO daily and Nintedanib at 150 mg PO bid Capecitabine at 2000 mg/m2 will be administration will be twice daily for two weeks (the first 2 weeks of each 21 day cycle), followed by a 1 week rest. Nintedanib 150 mg will be administered twice daily for 21 days (i.e., 1 complete 3-week cycle). Both capecitabine and nintedanib may be taken together, with water, within 30 minutes following a meal. Doses should be separated by approximately 12 hours, with the PM dose being 12 hours (+/- 2 hours) after the AM dose. Dose Level (Arm) 2: Capecitabine at 2000 mg/m2 PO daily and Nintedanib at 200 mg PO bid Capecitabine at 2000 mg/m2 will be administration will be twice daily for two weeks (the first 2 weeks of each 21 day cycle), followed by a 1 week rest. Nintedanib 2000 mg will be administered twice daily for 21 days (i.e., 1 complete 3-week cycle). Both capecitabine and nintedanib may be taken together, with water, within 30 minutes following a meal. Doses should be separated by approximately 12 hours, with the PM dose being 12 hours (+/- 2 hours) after the AM dose.
    All Cause Mortality
    Dose Level 1: Capecitabine at 2000 mg/m2, Nintedanib at 150 mg Dose Level 2: Capecitabine at 2000 mg/m2,Nintedanib at 200 mg
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 3/3 (100%) 32/39 (82.1%)
    Serious Adverse Events
    Dose Level 1: Capecitabine at 2000 mg/m2, Nintedanib at 150 mg Dose Level 2: Capecitabine at 2000 mg/m2,Nintedanib at 200 mg
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/3 (0%) 10/39 (25.6%)
    Gastrointestinal disorders
    Abdominal pain 0/3 (0%) 0 1/39 (2.6%) 1
    Constipation 0/3 (0%) 0 1/39 (2.6%) 1
    Intestinal perforation 0/3 (0%) 0 1/39 (2.6%) 1
    Small intestinal obstruction 0/3 (0%) 0 1/39 (2.6%) 1
    Hepatobiliary disorders
    Hepatic failure 0/3 (0%) 0 1/39 (2.6%) 1
    Infections and infestations
    Gastroenteritis 0/3 (0%) 0 1/39 (2.6%) 1
    Sepsis 0/3 (0%) 0 1/39 (2.6%) 1
    Investigations
    Alanine aminotransferase increased 0/3 (0%) 0 1/39 (2.6%) 1
    Metabolism and nutrition disorders
    Dehydration 0/3 (0%) 0 1/39 (2.6%) 1
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Metastases to central nervous system 0/3 (0%) 0 1/39 (2.6%) 1
    Neoplasm malignant 0/3 (0%) 0 1/39 (2.6%) 1
    Psychiatric disorders
    Mental status changes 0/3 (0%) 0 1/39 (2.6%) 1
    Renal and urinary disorders
    Urinary retention 0/3 (0%) 0 1/39 (2.6%) 1
    Respiratory, thoracic and mediastinal disorders
    Pleural effusion 0/3 (0%) 0 1/39 (2.6%) 2
    Respiratory failure 0/3 (0%) 0 1/39 (2.6%) 2
    Other (Not Including Serious) Adverse Events
    Dose Level 1: Capecitabine at 2000 mg/m2, Nintedanib at 150 mg Dose Level 2: Capecitabine at 2000 mg/m2,Nintedanib at 200 mg
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 3/3 (100%) 39/39 (100%)
    Blood and lymphatic system disorders
    Anaemia 1/3 (33.3%) 1 14/39 (35.9%) 25
    Lymphadenopathy 0/3 (0%) 0 1/39 (2.6%) 1
    Lymphopenia 0/3 (0%) 0 5/39 (12.8%) 8
    Thrombocytopenia 0/3 (0%) 0 1/39 (2.6%) 1
    Cardiac disorders
    Cardiac disorder 0/3 (0%) 0 2/39 (5.1%) 2
    Pericardial effusion 0/3 (0%) 0 1/39 (2.6%) 1
    Tachycardia 0/3 (0%) 0 1/39 (2.6%) 1
    Eye disorders
    Dry eye 0/3 (0%) 0 1/39 (2.6%) 1
    Eye irritation 0/3 (0%) 0 1/39 (2.6%) 1
    Lacrimation increased 0/3 (0%) 0 2/39 (5.1%) 2
    Ocular hyperaemia 0/3 (0%) 0 1/39 (2.6%) 1
    Vision blurred 0/3 (0%) 0 3/39 (7.7%) 3
    Gastrointestinal disorders
    Abdominal discomfort 0/3 (0%) 0 1/39 (2.6%) 1
    Abdominal distension 0/3 (0%) 0 5/39 (12.8%) 6
    Abdominal pain 1/3 (33.3%) 1 10/39 (25.6%) 10
    Abdominal pain upper 0/3 (0%) 0 3/39 (7.7%) 3
    Ascites 1/3 (33.3%) 1 2/39 (5.1%) 2
    Cheilitis 0/3 (0%) 0 1/39 (2.6%) 1
    Colitis 0/3 (0%) 0 1/39 (2.6%) 1
    Constipation 1/3 (33.3%) 1 11/39 (28.2%) 14
    Diarrhoea 2/3 (66.7%) 4 22/39 (56.4%) 49
    Dry mouth 0/3 (0%) 0 3/39 (7.7%) 3
    Flatulence 1/3 (33.3%) 1 3/39 (7.7%) 3
    Gastrooesophageal reflux disease 0/3 (0%) 0 1/39 (2.6%) 1
    Gingival bleeding 0/3 (0%) 0 1/39 (2.6%) 1
    Haematochezia 0/3 (0%) 0 2/39 (5.1%) 2
    Haemorrhoids 0/3 (0%) 0 1/39 (2.6%) 1
    Large intestinal obstruction 0/3 (0%) 0 1/39 (2.6%) 1
    Nausea 3/3 (100%) 6 27/39 (69.2%) 45
    Oral pain 0/3 (0%) 0 2/39 (5.1%) 2
    Rectal haemorrhage 0/3 (0%) 0 1/39 (2.6%) 1
    Salivary hypersecretion 0/3 (0%) 0 1/39 (2.6%) 1
    Small intestinal obstruction 0/3 (0%) 0 1/39 (2.6%) 1
    Stomatitis 2/3 (66.7%) 7 5/39 (12.8%) 5
    Vomiting 3/3 (100%) 3 26/39 (66.7%) 45
    General disorders
    Asthenia 0/3 (0%) 0 2/39 (5.1%) 2
    Chills 0/3 (0%) 0 3/39 (7.7%) 3
    Fatigue 3/3 (100%) 4 23/39 (59%) 48
    Influenza like illness 0/3 (0%) 0 1/39 (2.6%) 1
    Medical device pain 0/3 (0%) 0 1/39 (2.6%) 1
    Mucosal inflammation 0/3 (0%) 0 2/39 (5.1%) 4
    Non-cardiac chest pain 1/3 (33.3%) 1 1/39 (2.6%) 2
    Oedema 0/3 (0%) 0 1/39 (2.6%) 1
    Oedema peripheral 0/3 (0%) 0 2/39 (5.1%) 2
    Pain 0/3 (0%) 0 1/39 (2.6%) 1
    Pyrexia 1/3 (33.3%) 2 6/39 (15.4%) 6
    Swelling 0/3 (0%) 0 1/39 (2.6%) 1
    Hepatobiliary disorders
    Biliary colic 0/3 (0%) 0 1/39 (2.6%) 1
    Hyperbilirubinaemia 1/3 (33.3%) 1 3/39 (7.7%) 6
    Infections and infestations
    Bronchitis 0/3 (0%) 0 1/39 (2.6%) 1
    Influenza 0/3 (0%) 0 1/39 (2.6%) 1
    Legionella infection 0/3 (0%) 0 1/39 (2.6%) 1
    Nasopharyngitis 1/3 (33.3%) 1 1/39 (2.6%) 1
    Pneumonia 0/3 (0%) 0 2/39 (5.1%) 3
    Urinary tract infection 1/3 (33.3%) 2 1/39 (2.6%) 1
    Urinary tract infection enterococcal 0/3 (0%) 0 1/39 (2.6%) 1
    Viral infection 0/3 (0%) 0 1/39 (2.6%) 1
    Injury, poisoning and procedural complications
    Contusion 0/3 (0%) 0 1/39 (2.6%) 1
    Fall 1/3 (33.3%) 1 1/39 (2.6%) 1
    Spinal fracture 1/3 (33.3%) 1 0/39 (0%) 0
    Traumatic haematoma 0/3 (0%) 0 1/39 (2.6%) 1
    Investigations
    Alanine aminotransferase 0/3 (0%) 0 1/39 (2.6%) 1
    Alanine aminotransferase increased 0/3 (0%) 0 16/39 (41%) 23
    Aspartate aminotransferase 0/3 (0%) 0 2/39 (5.1%) 2
    Aspartate aminotransferase increased 3/3 (100%) 4 19/39 (48.7%) 31
    Blood albumin decreased 0/3 (0%) 0 1/39 (2.6%) 1
    Blood alkaline phosphatase 0/3 (0%) 0 1/39 (2.6%) 1
    Blood alkaline phosphatase increased 0/3 (0%) 0 16/39 (41%) 25
    Blood bilirubin increased 0/3 (0%) 0 10/39 (25.6%) 16
    Blood creatinine increased 0/3 (0%) 0 1/39 (2.6%) 5
    Blood sodium decreased 0/3 (0%) 0 1/39 (2.6%) 1
    Neutrophil count decreased 0/3 (0%) 0 1/39 (2.6%) 1
    Platelet count 0/3 (0%) 0 1/39 (2.6%) 1
    Platelet count decreased 0/3 (0%) 0 2/39 (5.1%) 3
    Serum ferritin decreased 0/3 (0%) 0 1/39 (2.6%) 1
    Transferrin saturation decreased 0/3 (0%) 0 1/39 (2.6%) 1
    Urine protein, quantitative 0/3 (0%) 0 1/39 (2.6%) 1
    Weight decreased 1/3 (33.3%) 1 7/39 (17.9%) 10
    White blood cell count decreased 0/3 (0%) 0 5/39 (12.8%) 7
    Metabolism and nutrition disorders
    Decreased appetite 1/3 (33.3%) 2 16/39 (41%) 27
    Dehydration 0/3 (0%) 0 4/39 (10.3%) 4
    Electrolyte imbalance 0/3 (0%) 0 1/39 (2.6%) 1
    Hypercalcaemia 0/3 (0%) 0 1/39 (2.6%) 1
    Hyperglycaemia 1/3 (33.3%) 1 2/39 (5.1%) 2
    Hyperkalaemia 0/3 (0%) 0 1/39 (2.6%) 1
    Hypernatraemia 0/3 (0%) 0 2/39 (5.1%) 2
    Hyperuricaemia 0/3 (0%) 0 1/39 (2.6%) 1
    Hypoalbuminaemia 0/3 (0%) 0 11/39 (28.2%) 25
    Hypocalcaemia 0/3 (0%) 0 2/39 (5.1%) 2
    Hypokalaemia 0/3 (0%) 0 5/39 (12.8%) 9
    Hyponatraemia 1/3 (33.3%) 1 10/39 (25.6%) 13
    Hypophosphataemia 0/3 (0%) 0 1/39 (2.6%) 1
    Musculoskeletal and connective tissue disorders
    Arthralgia 0/3 (0%) 0 4/39 (10.3%) 4
    Back pain 0/3 (0%) 0 5/39 (12.8%) 7
    Bone pain 0/3 (0%) 0 1/39 (2.6%) 1
    Flank pain 0/3 (0%) 0 1/39 (2.6%) 1
    Muscular weakness 1/3 (33.3%) 2 3/39 (7.7%) 4
    Musculoskeletal discomfort 0/3 (0%) 0 1/39 (2.6%) 1
    Musculoskeletal pain 0/3 (0%) 0 1/39 (2.6%) 2
    Myalgia 0/3 (0%) 0 2/39 (5.1%) 2
    Neck pain 0/3 (0%) 0 1/39 (2.6%) 1
    Pain in extremity 0/3 (0%) 0 3/39 (7.7%) 3
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Bone marrow leukaemic cell infiltration 0/3 (0%) 0 1/39 (2.6%) 1
    Nervous system disorders
    Dizziness 0/3 (0%) 0 8/39 (20.5%) 8
    Dysarthria 1/3 (33.3%) 1 1/39 (2.6%) 1
    Dysgeusia 1/3 (33.3%) 1 0/39 (0%) 0
    Headache 0/3 (0%) 0 8/39 (20.5%) 9
    Lethargy 0/3 (0%) 0 1/39 (2.6%) 1
    Neuropathy peripheral 1/3 (33.3%) 1 9/39 (23.1%) 10
    Paraesthesia 0/3 (0%) 0 1/39 (2.6%) 1
    Taste disorder 0/3 (0%) 0 4/39 (10.3%) 4
    Psychiatric disorders
    Anxiety 0/3 (0%) 0 2/39 (5.1%) 2
    Catatonia 0/3 (0%) 0 1/39 (2.6%) 1
    Confusional state 0/3 (0%) 0 1/39 (2.6%) 1
    Mental disorder 0/3 (0%) 0 1/39 (2.6%) 1
    Renal and urinary disorders
    Acute kidney injury 0/3 (0%) 0 1/39 (2.6%) 1
    Haematuria 0/3 (0%) 0 2/39 (5.1%) 7
    Nephrolithiasis 0/3 (0%) 0 1/39 (2.6%) 1
    Proteinuria 0/3 (0%) 0 2/39 (5.1%) 3
    Renal injury 0/3 (0%) 0 1/39 (2.6%) 1
    Respiratory, thoracic and mediastinal disorders
    Chronic obstructive pulmonary disease 0/3 (0%) 0 1/39 (2.6%) 1
    Cough 0/3 (0%) 0 8/39 (20.5%) 12
    Dyspnoea 2/3 (66.7%) 3 8/39 (20.5%) 11
    Epistaxis 0/3 (0%) 0 1/39 (2.6%) 1
    Haemoptysis 0/3 (0%) 0 1/39 (2.6%) 1
    Nasal congestion 0/3 (0%) 0 1/39 (2.6%) 1
    Oropharyngeal pain 0/3 (0%) 0 3/39 (7.7%) 3
    Pleural effusion 0/3 (0%) 0 4/39 (10.3%) 4
    Pneumonitis 0/3 (0%) 0 1/39 (2.6%) 1
    Productive cough 0/3 (0%) 0 2/39 (5.1%) 2
    Pulmonary embolism 0/3 (0%) 0 2/39 (5.1%) 2
    Rhinorrhoea 0/3 (0%) 0 1/39 (2.6%) 1
    Upper-airway cough syndrome 0/3 (0%) 0 1/39 (2.6%) 1
    Skin and subcutaneous tissue disorders
    Alopecia 0/3 (0%) 0 1/39 (2.6%) 1
    Blister 0/3 (0%) 0 1/39 (2.6%) 1
    Dry skin 0/3 (0%) 0 8/39 (20.5%) 9
    Erythema 0/3 (0%) 0 3/39 (7.7%) 3
    Nail disorder 0/3 (0%) 0 2/39 (5.1%) 2
    Night sweats 0/3 (0%) 0 1/39 (2.6%) 1
    Palmar-plantar erythrodysaesthesia syndrome 2/3 (66.7%) 11 15/39 (38.5%) 36
    Pruritus 0/3 (0%) 0 2/39 (5.1%) 2
    Rash 0/3 (0%) 0 1/39 (2.6%) 1
    Rash papular 0/3 (0%) 0 1/39 (2.6%) 1
    Skin disorder 0/3 (0%) 0 2/39 (5.1%) 2
    Skin exfoliation 0/3 (0%) 0 3/39 (7.7%) 3
    Skin hyperpigmentation 0/3 (0%) 0 1/39 (2.6%) 1
    Skin hypertrophy 0/3 (0%) 0 1/39 (2.6%) 1
    Vascular disorders
    Deep vein thrombosis 0/3 (0%) 0 3/39 (7.7%) 3
    Hot flush 0/3 (0%) 0 2/39 (5.1%) 2
    Hypertension 2/3 (66.7%) 7 9/39 (23.1%) 32

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    All Principal Investigators ARE employed by the organization sponsoring the study.

    There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

    Results Point of Contact

    Name/Title Senior Administrator, Compliance - Clinical Research Services
    Organization Roswell Park Cancer Institute
    Phone 716-845-2300
    Email Adrienne.Groman@RoswellPark.org
    Responsible Party:
    Roswell Park Cancer Institute
    ClinicalTrials.gov Identifier:
    NCT02393755
    Other Study ID Numbers:
    • I 265514
    • NCI-2015-00223
    • I 265514
    • P30CA016056
    First Posted:
    Mar 19, 2015
    Last Update Posted:
    Jul 8, 2021
    Last Verified:
    Jul 1, 2021