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
Enrollment
2
Locations
2
Arms
72.3
Actual Duration (Months)
21
Patients Per Site
0.3
Patients Per Site Per Month

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

ArmIntervention/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

    SiteCityStateCountryPostal Code
    1City of Hope Comprehensive Cancer CenterDuarteCaliforniaUnited States91010
    2Roswell Park Cancer InstituteBuffaloNew YorkUnited States14263

    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 TitleDose Level 1: Capecitabine at 2000 mg/2, Nintedanib at 150 mgDose Level 2: Capecitabine at 2000 mg/m2, Nintedanib at 200 mg
    Arm/Group DescriptionDose 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
    STARTED339
    COMPLETED332
    NOT COMPLETED07

    Baseline Characteristics

    Arm/Group TitleDose Level 1: Capecitabine at 2000 mg/m2, Nintedanib at 150 mgDose Level 2: Capecitabine at 2000 mg/m2,Nintedanib at 200 mgTotal
    Arm/Group DescriptionDose 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 Participants33942
    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
    TitleTo Examine the DLT
    DescriptionThe 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 FrameAt least 21 days.

    Outcome Measure Data

    Analysis Population Description
    Patients who were evaluable for DLTs
    Arm/Group TitleTreatment (Capecitabine, Nintedanib)
    Arm/Group DescriptionPatients 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 Participants9
    Number [mg]
    200
    2. Primary Outcome
    TitleProgression Free Survival (PFS) Rate, Defined as the Proportion of Patients Who Survive Without Disease Progression Via the RECIST Version 1.1 (Phase II)
    DescriptionProgressive 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 FrameAt 18 weeks

    Outcome Measure Data

    Analysis Population Description
    All treated and eligible patients at dose level 2
    Arm/Group TitleTreatment (Capecitabine, Nintedanib)
    Arm/Group DescriptionPatients 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 Participants36
    Number (90% Confidence Interval) [percentage of participants]
    41.7
    1390%
    3. Secondary Outcome
    TitleMedian PFS (Phase II)
    DescriptionProgressive 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 FrameUp to 2 years

    Outcome Measure Data

    Analysis Population Description
    All treated and eligible patients at dose level 2
    Arm/Group TitleTreatment (Capecitabine, Nintedanib)
    Arm/Group DescriptionPatients 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 Participants36
    Median (90% Confidence Interval) [months]
    3.4
    4. Secondary Outcome
    TitleMedian OS (Phase II)
    DescriptionOverall 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 FrameFrom 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 TitleTreatment (Capecitabine, Nintedanib)
    Arm/Group DescriptionPatients 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 Participants36
    Median (90% Confidence Interval) [months]
    8.9
    5. Secondary Outcome
    TitleObjective Response Rate
    DescriptionOverall 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 FrameAfter every 3 cycles (9 weeks) of therapy.

    Outcome Measure Data

    Analysis Population Description
    All treated and eligible patients at dose level 2
    Arm/Group TitleTreatment (Capecitabine, Nintedanib)
    Arm/Group DescriptionPatients 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 Participants36
    Number (90% Confidence Interval) [percentage of participants]
    58.3
    1943.3%
    6. Secondary Outcome
    TitleAggregate Rates of Adverse Events Measured by CTCAE Version 4.0 (Phase II)
    DescriptionNumber of Participants with Adverse Events, Graded According to the CTEP NCI Common Terminology Criteria for Adverse Events (CTCAE Version 4.0).
    Time FrameUp 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 TitleTreatment (Capecitabine, Nintedanib)
    Arm/Group DescriptionPatients 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 Participants36
    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 FrameDay 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 TitleDose Level 1: Capecitabine at 2000 mg/m2, Nintedanib at 150 mgDose Level 2: Capecitabine at 2000 mg/m2,Nintedanib at 200 mg
    Arm/Group DescriptionDose 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 mgDose Level 2: Capecitabine at 2000 mg/m2,Nintedanib at 200 mg
    Affected / at Risk (%)# EventsAffected / at Risk (%)# Events
    Total3/3 (100%) 32/39 (82.1%)
    Serious Adverse Events
    Dose Level 1: Capecitabine at 2000 mg/m2, Nintedanib at 150 mgDose Level 2: Capecitabine at 2000 mg/m2,Nintedanib at 200 mg
    Affected / at Risk (%)# EventsAffected / at Risk (%)# Events
    Total0/3 (0%) 10/39 (25.6%)
    Gastrointestinal disorders
    Abdominal pain0/3 (0%) 01/39 (2.6%) 1
    Constipation0/3 (0%) 01/39 (2.6%) 1
    Intestinal perforation0/3 (0%) 01/39 (2.6%) 1
    Small intestinal obstruction0/3 (0%) 01/39 (2.6%) 1
    Hepatobiliary disorders
    Hepatic failure0/3 (0%) 01/39 (2.6%) 1
    Infections and infestations
    Gastroenteritis0/3 (0%) 01/39 (2.6%) 1
    Sepsis0/3 (0%) 01/39 (2.6%) 1
    Investigations
    Alanine aminotransferase increased0/3 (0%) 01/39 (2.6%) 1
    Metabolism and nutrition disorders
    Dehydration0/3 (0%) 01/39 (2.6%) 1
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Metastases to central nervous system0/3 (0%) 01/39 (2.6%) 1
    Neoplasm malignant0/3 (0%) 01/39 (2.6%) 1
    Psychiatric disorders
    Mental status changes0/3 (0%) 01/39 (2.6%) 1
    Renal and urinary disorders
    Urinary retention0/3 (0%) 01/39 (2.6%) 1
    Respiratory, thoracic and mediastinal disorders
    Pleural effusion0/3 (0%) 01/39 (2.6%) 2
    Respiratory failure0/3 (0%) 01/39 (2.6%) 2
    Other (Not Including Serious) Adverse Events
    Dose Level 1: Capecitabine at 2000 mg/m2, Nintedanib at 150 mgDose Level 2: Capecitabine at 2000 mg/m2,Nintedanib at 200 mg
    Affected / at Risk (%)# EventsAffected / at Risk (%)# Events
    Total3/3 (100%) 39/39 (100%)
    Blood and lymphatic system disorders
    Anaemia1/3 (33.3%) 114/39 (35.9%) 25
    Lymphadenopathy0/3 (0%) 01/39 (2.6%) 1
    Lymphopenia0/3 (0%) 05/39 (12.8%) 8
    Thrombocytopenia0/3 (0%) 01/39 (2.6%) 1
    Cardiac disorders
    Cardiac disorder0/3 (0%) 02/39 (5.1%) 2
    Pericardial effusion0/3 (0%) 01/39 (2.6%) 1
    Tachycardia0/3 (0%) 01/39 (2.6%) 1
    Eye disorders
    Dry eye0/3 (0%) 01/39 (2.6%) 1
    Eye irritation0/3 (0%) 01/39 (2.6%) 1
    Lacrimation increased0/3 (0%) 02/39 (5.1%) 2
    Ocular hyperaemia0/3 (0%) 01/39 (2.6%) 1
    Vision blurred0/3 (0%) 03/39 (7.7%) 3
    Gastrointestinal disorders
    Abdominal discomfort0/3 (0%) 01/39 (2.6%) 1
    Abdominal distension0/3 (0%) 05/39 (12.8%) 6
    Abdominal pain1/3 (33.3%) 110/39 (25.6%) 10
    Abdominal pain upper0/3 (0%) 03/39 (7.7%) 3
    Ascites1/3 (33.3%) 12/39 (5.1%) 2
    Cheilitis0/3 (0%) 01/39 (2.6%) 1
    Colitis0/3 (0%) 01/39 (2.6%) 1
    Constipation1/3 (33.3%) 111/39 (28.2%) 14
    Diarrhoea2/3 (66.7%) 422/39 (56.4%) 49
    Dry mouth0/3 (0%) 03/39 (7.7%) 3
    Flatulence1/3 (33.3%) 13/39 (7.7%) 3
    Gastrooesophageal reflux disease0/3 (0%) 01/39 (2.6%) 1
    Gingival bleeding0/3 (0%) 01/39 (2.6%) 1
    Haematochezia0/3 (0%) 02/39 (5.1%) 2
    Haemorrhoids0/3 (0%) 01/39 (2.6%) 1
    Large intestinal obstruction0/3 (0%) 01/39 (2.6%) 1
    Nausea3/3 (100%) 627/39 (69.2%) 45
    Oral pain0/3 (0%) 02/39 (5.1%) 2
    Rectal haemorrhage0/3 (0%) 01/39 (2.6%) 1
    Salivary hypersecretion0/3 (0%) 01/39 (2.6%) 1
    Small intestinal obstruction0/3 (0%) 01/39 (2.6%) 1
    Stomatitis2/3 (66.7%) 75/39 (12.8%) 5
    Vomiting3/3 (100%) 326/39 (66.7%) 45
    General disorders
    Asthenia0/3 (0%) 02/39 (5.1%) 2
    Chills0/3 (0%) 03/39 (7.7%) 3
    Fatigue3/3 (100%) 423/39 (59%) 48
    Influenza like illness0/3 (0%) 01/39 (2.6%) 1
    Medical device pain0/3 (0%) 01/39 (2.6%) 1
    Mucosal inflammation0/3 (0%) 02/39 (5.1%) 4
    Non-cardiac chest pain1/3 (33.3%) 11/39 (2.6%) 2
    Oedema0/3 (0%) 01/39 (2.6%) 1
    Oedema peripheral0/3 (0%) 02/39 (5.1%) 2
    Pain0/3 (0%) 01/39 (2.6%) 1
    Pyrexia1/3 (33.3%) 26/39 (15.4%) 6
    Swelling0/3 (0%) 01/39 (2.6%) 1
    Hepatobiliary disorders
    Biliary colic0/3 (0%) 01/39 (2.6%) 1
    Hyperbilirubinaemia1/3 (33.3%) 13/39 (7.7%) 6
    Infections and infestations
    Bronchitis0/3 (0%) 01/39 (2.6%) 1
    Influenza0/3 (0%) 01/39 (2.6%) 1
    Legionella infection0/3 (0%) 01/39 (2.6%) 1
    Nasopharyngitis1/3 (33.3%) 11/39 (2.6%) 1
    Pneumonia0/3 (0%) 02/39 (5.1%) 3
    Urinary tract infection1/3 (33.3%) 21/39 (2.6%) 1
    Urinary tract infection enterococcal0/3 (0%) 01/39 (2.6%) 1
    Viral infection0/3 (0%) 01/39 (2.6%) 1
    Injury, poisoning and procedural complications
    Contusion0/3 (0%) 01/39 (2.6%) 1
    Fall1/3 (33.3%) 11/39 (2.6%) 1
    Spinal fracture1/3 (33.3%) 10/39 (0%) 0
    Traumatic haematoma0/3 (0%) 01/39 (2.6%) 1
    Investigations
    Alanine aminotransferase0/3 (0%) 01/39 (2.6%) 1
    Alanine aminotransferase increased0/3 (0%) 016/39 (41%) 23
    Aspartate aminotransferase0/3 (0%) 02/39 (5.1%) 2
    Aspartate aminotransferase increased3/3 (100%) 419/39 (48.7%) 31
    Blood albumin decreased0/3 (0%) 01/39 (2.6%) 1
    Blood alkaline phosphatase0/3 (0%) 01/39 (2.6%) 1
    Blood alkaline phosphatase increased0/3 (0%) 016/39 (41%) 25
    Blood bilirubin increased0/3 (0%) 010/39 (25.6%) 16
    Blood creatinine increased0/3 (0%) 01/39 (2.6%) 5
    Blood sodium decreased0/3 (0%) 01/39 (2.6%) 1
    Neutrophil count decreased0/3 (0%) 01/39 (2.6%) 1
    Platelet count0/3 (0%) 01/39 (2.6%) 1
    Platelet count decreased0/3 (0%) 02/39 (5.1%) 3
    Serum ferritin decreased0/3 (0%) 01/39 (2.6%) 1
    Transferrin saturation decreased0/3 (0%) 01/39 (2.6%) 1
    Urine protein, quantitative0/3 (0%) 01/39 (2.6%) 1
    Weight decreased1/3 (33.3%) 17/39 (17.9%) 10
    White blood cell count decreased0/3 (0%) 05/39 (12.8%) 7
    Metabolism and nutrition disorders
    Decreased appetite1/3 (33.3%) 216/39 (41%) 27
    Dehydration0/3 (0%) 04/39 (10.3%) 4
    Electrolyte imbalance0/3 (0%) 01/39 (2.6%) 1
    Hypercalcaemia0/3 (0%) 01/39 (2.6%) 1
    Hyperglycaemia1/3 (33.3%) 12/39 (5.1%) 2
    Hyperkalaemia0/3 (0%) 01/39 (2.6%) 1
    Hypernatraemia0/3 (0%) 02/39 (5.1%) 2
    Hyperuricaemia0/3 (0%) 01/39 (2.6%) 1
    Hypoalbuminaemia0/3 (0%) 011/39 (28.2%) 25
    Hypocalcaemia0/3 (0%) 02/39 (5.1%) 2
    Hypokalaemia0/3 (0%) 05/39 (12.8%) 9
    Hyponatraemia1/3 (33.3%) 110/39 (25.6%) 13
    Hypophosphataemia0/3 (0%) 01/39 (2.6%) 1
    Musculoskeletal and connective tissue disorders
    Arthralgia0/3 (0%) 04/39 (10.3%) 4
    Back pain0/3 (0%) 05/39 (12.8%) 7
    Bone pain0/3 (0%) 01/39 (2.6%) 1
    Flank pain0/3 (0%) 01/39 (2.6%) 1
    Muscular weakness1/3 (33.3%) 23/39 (7.7%) 4
    Musculoskeletal discomfort0/3 (0%) 01/39 (2.6%) 1
    Musculoskeletal pain0/3 (0%) 01/39 (2.6%) 2
    Myalgia0/3 (0%) 02/39 (5.1%) 2
    Neck pain0/3 (0%) 01/39 (2.6%) 1
    Pain in extremity0/3 (0%) 03/39 (7.7%) 3
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Bone marrow leukaemic cell infiltration0/3 (0%) 01/39 (2.6%) 1
    Nervous system disorders
    Dizziness0/3 (0%) 08/39 (20.5%) 8
    Dysarthria1/3 (33.3%) 11/39 (2.6%) 1
    Dysgeusia1/3 (33.3%) 10/39 (0%) 0
    Headache0/3 (0%) 08/39 (20.5%) 9
    Lethargy0/3 (0%) 01/39 (2.6%) 1
    Neuropathy peripheral1/3 (33.3%) 19/39 (23.1%) 10
    Paraesthesia0/3 (0%) 01/39 (2.6%) 1
    Taste disorder0/3 (0%) 04/39 (10.3%) 4
    Psychiatric disorders
    Anxiety0/3 (0%) 02/39 (5.1%) 2
    Catatonia0/3 (0%) 01/39 (2.6%) 1
    Confusional state0/3 (0%) 01/39 (2.6%) 1
    Mental disorder0/3 (0%) 01/39 (2.6%) 1
    Renal and urinary disorders
    Acute kidney injury0/3 (0%) 01/39 (2.6%) 1
    Haematuria0/3 (0%) 02/39 (5.1%) 7
    Nephrolithiasis0/3 (0%) 01/39 (2.6%) 1
    Proteinuria0/3 (0%) 02/39 (5.1%) 3
    Renal injury0/3 (0%) 01/39 (2.6%) 1
    Respiratory, thoracic and mediastinal disorders
    Chronic obstructive pulmonary disease0/3 (0%) 01/39 (2.6%) 1
    Cough0/3 (0%) 08/39 (20.5%) 12
    Dyspnoea2/3 (66.7%) 38/39 (20.5%) 11
    Epistaxis0/3 (0%) 01/39 (2.6%) 1
    Haemoptysis0/3 (0%) 01/39 (2.6%) 1
    Nasal congestion0/3 (0%) 01/39 (2.6%) 1
    Oropharyngeal pain0/3 (0%) 03/39 (7.7%) 3
    Pleural effusion0/3 (0%) 04/39 (10.3%) 4
    Pneumonitis0/3 (0%) 01/39 (2.6%) 1
    Productive cough0/3 (0%) 02/39 (5.1%) 2
    Pulmonary embolism0/3 (0%) 02/39 (5.1%) 2
    Rhinorrhoea0/3 (0%) 01/39 (2.6%) 1
    Upper-airway cough syndrome0/3 (0%) 01/39 (2.6%) 1
    Skin and subcutaneous tissue disorders
    Alopecia0/3 (0%) 01/39 (2.6%) 1
    Blister0/3 (0%) 01/39 (2.6%) 1
    Dry skin0/3 (0%) 08/39 (20.5%) 9
    Erythema0/3 (0%) 03/39 (7.7%) 3
    Nail disorder0/3 (0%) 02/39 (5.1%) 2
    Night sweats0/3 (0%) 01/39 (2.6%) 1
    Palmar-plantar erythrodysaesthesia syndrome2/3 (66.7%) 1115/39 (38.5%) 36
    Pruritus0/3 (0%) 02/39 (5.1%) 2
    Rash0/3 (0%) 01/39 (2.6%) 1
    Rash papular0/3 (0%) 01/39 (2.6%) 1
    Skin disorder0/3 (0%) 02/39 (5.1%) 2
    Skin exfoliation0/3 (0%) 03/39 (7.7%) 3
    Skin hyperpigmentation0/3 (0%) 01/39 (2.6%) 1
    Skin hypertrophy0/3 (0%) 01/39 (2.6%) 1
    Vascular disorders
    Deep vein thrombosis0/3 (0%) 03/39 (7.7%) 3
    Hot flush0/3 (0%) 02/39 (5.1%) 2
    Hypertension2/3 (66.7%) 79/39 (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/TitleSenior Administrator, Compliance - Clinical Research Services
    OrganizationRoswell Park Cancer Institute
    Phone716-845-2300
    EmailAdrienne.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