A Single Arm, Phase II Study of Simvastatin Plus XELOX and Bevacizumab as First-line Chemotherapy in Metastatic Colorectal Cancer Patients
Primary Purpose
Colorectal Cancer
Status
Completed
Phase
Phase 2
Locations
Korea, Republic of
Study Type
Interventional
Intervention
Simvastatin
Sponsored by
About this trial
This is an interventional treatment trial for Colorectal Cancer
Eligibility Criteria
Inclusion Criteria:
- Histologically-confirmed colorectal carcinoma
- Stage IV or recurrent colorectal cancer
- age ≥ 20 years
- ECOG performance status ≤1
- At least one measurable tumor mass according to RECIST 1.1
- Expected survival for approximately 12 weeks or longer
- No prior systemic chemotherapy
- At least 4 weeks later after surgery or radiotherapy
- At least 12 months after adjuvant chemotherapy
Exclusion Criteria:
- Prior statins therapy within 1-year from the date of study entry
- Prior chemotherapeutic treatment for metastatic colorectal cancer.
- Prior other anti-VEGF (vascular endothelial growth factor) or TKIs (Tyrosine kinase inhibitors) treatment
- Current, Known CNS(central nervous system) malignancy (history of completely resected or irradiated brain metastases by WBRT (whole-brain radiation therapy) or stereotactic radiosurgery allowed.
- Severe or unstable cardiac disease, including (for example) coronary artery disease requiring increased doses of anti-anginal medication and/or coronary angioplasty (including stent placement) within the preceding 24 months(congestive heart failure NYHA (New York Heart Association) III or IV, unstable angina pectoris, history of myocardial infarction within the last twelve months, significant arrhythmias)
- Past or current history (within the last 5 years prior to treatment start) of other malignancies except metastatic colorectal cancer (Patients with curatively treated basal and squamous cell carcinoma of the skin or in situ carcinoma of the cervix are eligible)
- Uncontrolled systemic illness such as DM (diabetes mellitus), hypertension, hypothyroidism and infection
- History of thromboembolic or hemorrhagic events within 6 months prior to treatment
- History of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess within 6 months prior to enrollment.
- Evidence of bleeding diathesis or coagulopathy
Sites / Locations
- Samsung Medical Center
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Simvastatin
Arm Description
Outcomes
Primary Outcome Measures
Progression free survival
Secondary Outcome Measures
Full Information
NCT ID
NCT02026583
First Posted
December 31, 2013
Last Updated
January 15, 2018
Sponsor
Samsung Medical Center
1. Study Identification
Unique Protocol Identification Number
NCT02026583
Brief Title
A Single Arm, Phase II Study of Simvastatin Plus XELOX and Bevacizumab as First-line Chemotherapy in Metastatic Colorectal Cancer Patients
Official Title
A Single Arm, Phase II Study of Simvastatin Plus XELOX and Bevacizumab as First-line Chemotherapy in Metastatic Colorectal Cancer Patients
Study Type
Interventional
2. Study Status
Record Verification Date
January 2018
Overall Recruitment Status
Completed
Study Start Date
December 2013 (Actual)
Primary Completion Date
April 28, 2017 (Actual)
Study Completion Date
April 28, 2017 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Samsung Medical Center
4. Oversight
5. Study Description
Brief Summary
Study Objectives 1) Primary Objective: Progression-free survival 2) Secondary Objectives:
overall survival
response rate
incidence, nature and severity of all adverse events
lipid lowering effect of simvastatin
exploratory biomarker analysis : angiopoietin 2, BiP (Binding protein), Hsp (Heat shck protein) 90α
Study hypothesis In our recent in vitro study, addition of simvastatin to bevacizumab reduced proliferation, migration, invasion and tumor formation of endothelial cell. Moreover, colorectal cancer cell media which was treated with simvastatin combined with bevacizumab inhibited endothelial cell invasion and it was associated with decreased mediator of angiogenesis, such as angiopoietin 2, BiP and HSP 90α.. Treatment with bevacizumab and simvastatin more reduced the growth of xenograft tumors compared with bevacizumab alone.
Assessments 1) Safety : physical examination, vital signs, body weight, ECOG (Eastern Cooperative Oncology Group) performance status, clinical laboratory evaluation (chemistry, blood cell count) and any AE (adverse effect) graded by using CTCAE (Common Toxicity Criteria for Adverse Effects ) v 4.0 2) Efficacy : progression-free survival and overall survival will be collected. Response rate according to RECIST (Response Evaluation Criteria in Solid Tumors) 1,1 guideline will also be evaluated 3) PFS (Progression free survival): time from randomization to tumor progression or death 4) OS (Overall survival) : time from randomization to death or last follow-up 5) Biomarker analysis; The correlation between blood level, protein expression of angiopoietin 2, BiP, Hsp90α and clinical response will be explored.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Colorectal Cancer
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
43 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Simvastatin
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Simvastatin
Primary Outcome Measure Information:
Title
Progression free survival
Time Frame
During treatment : up to 6weeks, off the treatment : up to 8weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
20 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Histologically-confirmed colorectal carcinoma
Stage IV or recurrent colorectal cancer
age ≥ 20 years
ECOG performance status ≤1
At least one measurable tumor mass according to RECIST 1.1
Expected survival for approximately 12 weeks or longer
No prior systemic chemotherapy
At least 4 weeks later after surgery or radiotherapy
At least 12 months after adjuvant chemotherapy
Exclusion Criteria:
Prior statins therapy within 1-year from the date of study entry
Prior chemotherapeutic treatment for metastatic colorectal cancer.
Prior other anti-VEGF (vascular endothelial growth factor) or TKIs (Tyrosine kinase inhibitors) treatment
Current, Known CNS(central nervous system) malignancy (history of completely resected or irradiated brain metastases by WBRT (whole-brain radiation therapy) or stereotactic radiosurgery allowed.
Severe or unstable cardiac disease, including (for example) coronary artery disease requiring increased doses of anti-anginal medication and/or coronary angioplasty (including stent placement) within the preceding 24 months(congestive heart failure NYHA (New York Heart Association) III or IV, unstable angina pectoris, history of myocardial infarction within the last twelve months, significant arrhythmias)
Past or current history (within the last 5 years prior to treatment start) of other malignancies except metastatic colorectal cancer (Patients with curatively treated basal and squamous cell carcinoma of the skin or in situ carcinoma of the cervix are eligible)
Uncontrolled systemic illness such as DM (diabetes mellitus), hypertension, hypothyroidism and infection
History of thromboembolic or hemorrhagic events within 6 months prior to treatment
History of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess within 6 months prior to enrollment.
Evidence of bleeding diathesis or coagulopathy
Facility Information:
Facility Name
Samsung Medical Center
City
Seoul
Country
Korea, Republic of
12. IPD Sharing Statement
Learn more about this trial
A Single Arm, Phase II Study of Simvastatin Plus XELOX and Bevacizumab as First-line Chemotherapy in Metastatic Colorectal Cancer Patients
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