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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

Primary Purpose

Colorectal Cancer

Status

Completed

Phase

Phase 2

Locations

Korea, Republic of

Study Type

Interventional

Intervention

Simvastatin

About this trial

This is an interventional treatment trial for Colorectal Cancer

Eligibility Criteria

20 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

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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