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A Single Arm, Phase II Study of Simvastatin Plus XELOX and Bevacizumab as First-line Chemotherapy in Metastatic Colorectal Cancer Patients

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02026583
Recruitment Status : Completed
First Posted : January 3, 2014
Last Update Posted : January 17, 2018
Information provided by (Responsible Party):
Won Ki Kang, Samsung Medical Center

Tracking Information
First Submitted Date  ICMJE December 31, 2013
First Posted Date  ICMJE January 3, 2014
Last Update Posted Date January 17, 2018
Actual Study Start Date  ICMJE December 2013
Actual Primary Completion Date April 28, 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 1, 2014)
Progression free survival [ Time Frame: During treatment : up to 6weeks, off the treatment : up to 8weeks ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
Descriptive Information
Brief Title  ICMJE A Single Arm, Phase II Study of Simvastatin Plus XELOX and Bevacizumab as First-line Chemotherapy in Metastatic Colorectal Cancer Patients
Official Title  ICMJE A Single Arm, Phase II Study of Simvastatin Plus XELOX and Bevacizumab as First-line Chemotherapy in Metastatic Colorectal Cancer Patients
Brief Summary
  1. Study Objectives 1) Primary Objective: Progression-free survival 2) Secondary Objectives:

    1. overall survival
    2. response rate
    3. incidence, nature and severity of all adverse events
    4. lipid lowering effect of simvastatin
    5. exploratory biomarker analysis : angiopoietin 2, BiP (Binding protein), Hsp (Heat shck protein) 90α
  2. 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.
  3. 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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Colorectal Cancer
Intervention  ICMJE Drug: Simvastatin
Study Arms  ICMJE Experimental: Simvastatin
Intervention: Drug: Simvastatin
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: January 15, 2018)
Original Estimated Enrollment  ICMJE
 (submitted: January 1, 2014)
Actual Study Completion Date  ICMJE April 28, 2017
Actual Primary Completion Date April 28, 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Histologically-confirmed colorectal carcinoma
  2. Stage IV or recurrent colorectal cancer
  3. age ≥ 20 years
  4. ECOG performance status ≤1
  5. At least one measurable tumor mass according to RECIST 1.1
  6. Expected survival for approximately 12 weeks or longer
  7. No prior systemic chemotherapy
  8. At least 4 weeks later after surgery or radiotherapy
  9. At least 12 months after adjuvant chemotherapy

Exclusion Criteria:

  1. Prior statins therapy within 1-year from the date of study entry
  2. Prior chemotherapeutic treatment for metastatic colorectal cancer.
  3. Prior other anti-VEGF (vascular endothelial growth factor) or TKIs (Tyrosine kinase inhibitors) treatment
  4. 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.
  5. 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)
  6. 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)
  7. Uncontrolled systemic illness such as DM (diabetes mellitus), hypertension, hypothyroidism and infection
  8. History of thromboembolic or hemorrhagic events within 6 months prior to treatment
  9. History of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess within 6 months prior to enrollment.
  10. Evidence of bleeding diathesis or coagulopathy
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 20 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Korea, Republic of
Removed Location Countries  
Administrative Information
NCT Number  ICMJE NCT02026583
Other Study ID Numbers  ICMJE IRB no : 2013-07-088
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Current Responsible Party Won Ki Kang, Samsung Medical Center
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Samsung Medical Center
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Samsung Medical Center
Verification Date January 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP