Clinical Trials List
Protocol Number1199.52
NCT Number(ClinicalTrials.gov Identfier)NCT02149108
2014-09-15 - 2016-12-31
Phase III
Terminated5
ICD-10C18.9
Malignant neoplasm of colon, unspecified
A Double-blind, Randomised, Placebo Controlled Phase III Study of Nintedanib Plus Best Supportive Care (BSC) Versus Placebo Plus BSC in Patients With Metastatic Colorectal Cancer Refractory to Standard Therapies.
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Trial Applicant
Boehringer Ingelheim
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Sponsor
Boehringer Ingelheim
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Trial scale
Multi-Regional Multi-Center
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Update
2025/08/20
Investigators and Locations
Co-Principal Investigator
- Wen-Chi Chou Division of Hematology & Oncology
- Jen-Shi Chen Division of Hematology & Oncology
- Hung-Chih Hsu Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
- 姜正愷 Division of Colorectal Surgery
- Tzeon-jye Chiou Division of Hematology & Oncology
- 張世慶 Division of Colorectal Surgery
- 藍苑慈 Division of Colorectal Surgery
- Chueh-Chuan Yen Division of Hematology & Oncology
- Wei-Shone Chen Division of Colorectal Surgery
- Hao-Wei Teng Division of Hematology & Oncology
- Jin-Hwang Liu Division of Hematology & Oncology
- 林資琛 Division of Colorectal Surgery
- Ming-Huang Chen Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
- FAN -FENG CHIANG Division of Colorectal Surgery
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
- Chih-Hung Hsu Division of Hematology & Oncology
- SHIH-HUNG YANG 未分科
- SHIH-HUNG YANG Division of Hematology & Oncology
- Ann-Lii Cheng Division of Hematology & Oncology
- TA-CHEN HUANG Division of Hematology & Oncology
- Chiun Hsu Division of Hematology & Oncology
- 林育麟 Division of Hematology & Oncology
- YU-YUN SHAO Division of Hematology & Oncology
- 張端瑩 Division of Hematology & Oncology
- 呂理駿 Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Terminated
Condition/Disease
Colorectal cancer
Objectives
The objective of this Phase III study is to evaluate the efficacy of nintedanib in patients with metastatic colorectal cancer (mCRC) after failure of previous treatment with standard chemotherapy and biological agents.
Test Drug
Nintedanib (BIBF 1120)
Active Ingredient
Nintedanib
Dosage Form
soft capsule
Dosage
100 / 150
Endpoints
Primary Outcome Measures :
Progression-Free Survival (PFS) by Central Review Assessment [ Time Frame: From randomisation until cut-off date 14JUN2016. ]
PFS by central review assessment was defined as the time from the date of randomisation to the date of disease progression according to Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1 or death from any cause, whichever occurred first.
Median, 95% Confidence Interval were calculated from an unadjusted Kaplan-Meier curve for each treatment arm.
Overall Survival (OS) [ Time Frame: From randomisation until cut-off date 14JUN2016. ]
OS was defined as the time from randomisation to the time of death from any cause.
Median, 95% Confidence Interval were calculated from an unadjusted Kaplan-Meier curve for each treatment arm.
Secondary Outcome Measures :
Objective Tumour Response (Complete Response (CR)) + Partial Response (PR) by Central Review Assessment [ Time Frame: From randomisation until cut-off date 14JUN2016. ]
Objective tumour response was defined as best overall response of CR or PR determined by central review assessment.
Disease Control (Complete Response + Partial Response + Stable Disease) by Central Review Assessment [ Time Frame: From randomisation until cut-off date 14JUN2016. ]
Disease control was defined as best overall response of CR, PR, or Stable Disease (SD).
Progression-Free Survival (PFS) by Central Review Assessment [ Time Frame: From randomisation until cut-off date 14JUN2016. ]
PFS by central review assessment was defined as the time from the date of randomisation to the date of disease progression according to Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1 or death from any cause, whichever occurred first.
Median, 95% Confidence Interval were calculated from an unadjusted Kaplan-Meier curve for each treatment arm.
Overall Survival (OS) [ Time Frame: From randomisation until cut-off date 14JUN2016. ]
OS was defined as the time from randomisation to the time of death from any cause.
Median, 95% Confidence Interval were calculated from an unadjusted Kaplan-Meier curve for each treatment arm.
Secondary Outcome Measures :
Objective Tumour Response (Complete Response (CR)) + Partial Response (PR) by Central Review Assessment [ Time Frame: From randomisation until cut-off date 14JUN2016. ]
Objective tumour response was defined as best overall response of CR or PR determined by central review assessment.
Disease Control (Complete Response + Partial Response + Stable Disease) by Central Review Assessment [ Time Frame: From randomisation until cut-off date 14JUN2016. ]
Disease control was defined as best overall response of CR, PR, or Stable Disease (SD).
Inclution Criteria
Inclusion criteria:
Age >= 18 years
Signed informed consent
Histologically or cytologically confirmed colorectal adenocarcinoma
Metastatic or locally advanced disease not amenable to curative surgery and/or radiotherapy
Eastern Cooperative Oncology Group (ECOG) performance status = 1
At least one measurable lesion according to Response Evaluation Criteria In Solid Tumours (RECIST) version 1.1
Progression on standard therapies or withdrawn from standard treatment due to unacceptable toxicity. Previous standard treatment must include all of the following:
- fluoropyrimidine
- oxaliplatin: Patients treated with oxaliplatin in adjuvant setting should have progressed within 6 months of completion of adjuvant therapy or they must have been treated with oxaliplatin for metastatic disease
- irinotecan
- bevacizumab or aflibercept
- cetuximab or panitumumab for patients with K-Ras wt or Ras wt tumours
- The remaining standard available therapy as recommended by investigator is best supportive care (note: previous treatment with regorafenib and TAS 102 are allowed and these agents should be administered before study if available to patient according to local standards)
- Life expectancy of at least 12 weeks
- Hepatic function: aspartate aminotransferase (AST)/ Alanine Amino Transferase (ALT) = 1.5 X Upper Limit of Normal (ULN) and bilirubin = ULN for patients without liver metastases. AST/ALT = 2.5 X ULN and bilirubin = ULN for patients with liver metastases. Patients with Gilbert syndrome and bilirubin < 2 X ULN and normal AST/ALT are eligible
Coagulation parameters: International normalised ratio (INR) < 2 and partial prothrombin Time (PTT) = 2xULN
Age >= 18 years
Signed informed consent
Histologically or cytologically confirmed colorectal adenocarcinoma
Metastatic or locally advanced disease not amenable to curative surgery and/or radiotherapy
Eastern Cooperative Oncology Group (ECOG) performance status = 1
At least one measurable lesion according to Response Evaluation Criteria In Solid Tumours (RECIST) version 1.1
Progression on standard therapies or withdrawn from standard treatment due to unacceptable toxicity. Previous standard treatment must include all of the following:
- fluoropyrimidine
- oxaliplatin: Patients treated with oxaliplatin in adjuvant setting should have progressed within 6 months of completion of adjuvant therapy or they must have been treated with oxaliplatin for metastatic disease
- irinotecan
- bevacizumab or aflibercept
- cetuximab or panitumumab for patients with K-Ras wt or Ras wt tumours
- The remaining standard available therapy as recommended by investigator is best supportive care (note: previous treatment with regorafenib and TAS 102 are allowed and these agents should be administered before study if available to patient according to local standards)
- Life expectancy of at least 12 weeks
- Hepatic function: aspartate aminotransferase (AST)/ Alanine Amino Transferase (ALT) = 1.5 X Upper Limit of Normal (ULN) and bilirubin = ULN for patients without liver metastases. AST/ALT = 2.5 X ULN and bilirubin = ULN for patients with liver metastases. Patients with Gilbert syndrome and bilirubin < 2 X ULN and normal AST/ALT are eligible
Coagulation parameters: International normalised ratio (INR) < 2 and partial prothrombin Time (PTT) = 2xULN
Exclusion Criteria
Exclusion criteria:
Previous treatment with nintedanib
toxicity attributed to previous anticancer therapy that did not resolve to Common Terminology Criteria for Adverse Events (CTCAE) grade =1
History of other malignancies in the last 5 years, in particular those that could interfere with interpretation of results.
Serious concomitant disease or medical condition affecting compliance with trial requirements or which are considered relevant for the evaluation of the efficacy or safety of the trial drug,
Significant cardiovascular diseases
History of severe haemorrhagic or thromboembolic event in the past 12 months
Bleeding or thrombotic disorders requiring anticoagulant therapy such as warfarin, or similar agents requiring therapeutic INR monitoring
Gastrointestinal disorders or abnormalities that would interfere with absorption of study drug
Patient with brain metastases that are symptomatic and/or require therapy.
Patients of childbearing potential who are sexually active and unwilling to use a highly effective method of contraception
Pregnancy or breast-feeding.
Previous treatment with nintedanib
toxicity attributed to previous anticancer therapy that did not resolve to Common Terminology Criteria for Adverse Events (CTCAE) grade =1
History of other malignancies in the last 5 years, in particular those that could interfere with interpretation of results.
Serious concomitant disease or medical condition affecting compliance with trial requirements or which are considered relevant for the evaluation of the efficacy or safety of the trial drug,
Significant cardiovascular diseases
History of severe haemorrhagic or thromboembolic event in the past 12 months
Bleeding or thrombotic disorders requiring anticoagulant therapy such as warfarin, or similar agents requiring therapeutic INR monitoring
Gastrointestinal disorders or abnormalities that would interfere with absorption of study drug
Patient with brain metastases that are symptomatic and/or require therapy.
Patients of childbearing potential who are sexually active and unwilling to use a highly effective method of contraception
Pregnancy or breast-feeding.
The Estimated Number of Participants
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Taiwan
42 participants
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Global
800 participants
