Colorectal Neoplasms
Conditions
Brief summary
The objective of this Phase II study is to assess the efficacy and safety of nintedanib alone or in combination with capecitabine for patients with refractory metastatic colorectal cancer (mCRC) after failure of at least 2 lines of standard treatment
Interventions
DRUGNintedanib
DRUGCapecitabine
Sponsors
Boehringer Ingelheim
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 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 RECIST 1.1 * Previously treated with all of the following: fluoropyrimidine, (e.g. 5-fluorouracil (5-FU), capecitabine or TAS-102); 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; Vascular Endothelial Growth Factor (VEGF) directed treatment (e.g. bevacizumab, aflibercept, ramucirumab or regorafenib); cetuximab or panitumumab for patients with K-Ras wt or Ras wt tumors * Minimal time interval of 3 weeks between the last administration of Colorectal Cancer (CRC) treatment (cytotoxics or targeted agents) and starting of trial therapy * Adequate liver and kidney function * Further inclusion criteria apply
Exclusion criteria
* Prior treatment with nintedanib. * Any other investigational agent received within 3 weeks prior to randomization * Known hypersensitivity or intolerability to the trial drugs or their excipients * History of other malignancies in the last 5 years, in particular those that could interfere with interpretation of results. Patients with adequately treated basal or squamous cell skin cancer or cervix carcinoma and other early stage cancer treated curatively are eligible * History of severe or unexpected reactions to fluoropyrimidine therapy or any of its excipients * Known dihydropyrimidine dehydrogenase (DPD) deficiency * Treatment with sorivudine or its chemically related analogues, such as brivudine * 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, such as neurologic, psychiatric, infectious disease or active ulcers (gastro-intestinal tract, skin) or laboratory abnormality that may increase the risk associated with trial participation or trial drug administration, and in the judgment of the investigator would make the patient inappropriate for entry into the trial * Major injuries and/or surgery or bone fracture within 4 weeks of trial inclusion (signing Informed Consent), or planned surgical procedures during the trial period * Significant cardiovascular diseases (i.e. uncontrolled hypertension, unstable angina, history of myocardial infarction within past 6 months of trial inclusion, congestive heart failure \> New York Heart Association (NYHA) II) * History of severe hemorrhagic or thromboembolic event in the past 6 months (excluding central venous catheter thrombosis and peripheral deep vein thrombosis). Known inherited predisposition to bleeding or to thrombosis * Bleeding or thrombotic disorders requiring anticoagulant therapy such as warfarin, or similar agents requiring therapeuticInternational normalized ratio (INR) monitoring (treatment with low molecular weight heparin and/or heparin flush as needed for maintenance of an indwelling intravenous device is allowed) * Inflammatory bowel disease and other serious medical conditions increasing the risk of perforation or bleeding according to investigator's judgment * Gastrointestinal disorders or abnormalities that would interfere with absorption of study drug * Patient with brain metastases that are symptomatic and/or require therapy. Patients with previously treated and stable brain metastases are allowed * Further
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival (PFS) | Data collected up to cut-off date 09 Sep 2016, Up to 02 months | PFS is defined as the time from randomization until objective tumor progression or death. Since only one patient was enrolled prior to termination of the trial, no data summarization or analysis was carried out. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) | Data collected up to cut-off date 09 Sep 2016, Up to 02 months | Overall survival is defined as the time from randomization until death from any cause. Since only one patient was enrolled prior to termination of the trial, no data summarization or analysis was carried out. |
| Objective Response Rate (ORR) | tumor response was to be assessed by imaging according to RECIST (version 1.1) every 6 weeks. | ORR is defined as complete response (CR) or partial response (PR) per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Since only one patient was enrolled prior to termination of the trial, no data summarization or analysis was carried out. |
| Disease Control (DC) | Data collected up to cut-off date 09 Sep 2016, Up to 02 months | Disease control is defined as CR or PR or Stable disease (SD) per RECIST version 1.1. Since only one patient was enrolled prior to termination of the trial, no data summarization or analysis was carried out. |
| Percentage of Patients With Grade 3 or Worse Adverse Events | Data collected up to cut-off date 09 Sep 2016, Up to 02 months | Percentage of patients with grade 3 or worse adverse events. |
Countries
United States
Participant flow
Recruitment details
This was an exploratory, phase II multi-center, non-comparative, open-label, randomized trial to assess the efficacy and safety of nintedanib alone, or in combination with capecitabine in patients with refractory metastatic colorectal cancer.
Pre-assignment details
Patients eligible for this study were to be randomized in a 1:1 fashion to receive either nintedanib alone or combination with capecitabine. One patient with combination therapy entered study, no patient with nintedanib alone entered study.
Participants by arm
| Arm | Count |
|---|---|
| Nintedanib Plus Capecitabine Patients were to be orally administered tablets of Nintedanib and 1000 mg/m2 Capecitabine twice daily.
Nintedanib: 21 day cycles; Capecitabine: first 14 days of each 21 day cycle | 1 |
| Total | 1 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Progressive disease | 1 |
Baseline characteristics
| Characteristic | Nintedanib Plus Capecitabine |
|---|---|
| Age, Continuous | 50 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 1 Participants |
| Sex: Female, Male Female | 1 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 1 |
| other Total, other adverse events | 1 / 1 |
| serious Total, serious adverse events | 0 / 1 |
Outcome results
Primary
Progression Free Survival (PFS)
PFS is defined as the time from randomization until objective tumor progression or death. Since only one patient was enrolled prior to termination of the trial, no data summarization or analysis was carried out.
Time frame: Data collected up to cut-off date 09 Sep 2016, Up to 02 months
Population: Randomized set (RS): Comprising all patients who have a randomization date recorded in the electronic Case record form (eCRF).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Nintedanib Plus Capecitabine | Progression Free Survival (PFS) | NA months |
Secondary
Disease Control (DC)
Disease control is defined as CR or PR or Stable disease (SD) per RECIST version 1.1. Since only one patient was enrolled prior to termination of the trial, no data summarization or analysis was carried out.
Time frame: Data collected up to cut-off date 09 Sep 2016, Up to 02 months
Population: RS
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Nintedanib Plus Capecitabine | Disease Control (DC) | NA Percentage of participants |
Secondary
Objective Response Rate (ORR)
ORR is defined as complete response (CR) or partial response (PR) per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Since only one patient was enrolled prior to termination of the trial, no data summarization or analysis was carried out.
Time frame: tumor response was to be assessed by imaging according to RECIST (version 1.1) every 6 weeks.
Population: RS
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Nintedanib Plus Capecitabine | Objective Response Rate (ORR) | NA Percentage of participants |
Secondary
Overall Survival (OS)
Overall survival is defined as the time from randomization until death from any cause. Since only one patient was enrolled prior to termination of the trial, no data summarization or analysis was carried out.
Time frame: Data collected up to cut-off date 09 Sep 2016, Up to 02 months
Population: RS
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Nintedanib Plus Capecitabine | Overall Survival (OS) | NA months |
Secondary
Percentage of Patients With Grade 3 or Worse Adverse Events
Percentage of patients with grade 3 or worse adverse events.
Time frame: Data collected up to cut-off date 09 Sep 2016, Up to 02 months
Population: RS
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Nintedanib Plus Capecitabine | Percentage of Patients With Grade 3 or Worse Adverse Events | 0 Percentage of participants |