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

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.

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Key information

Conditions

Colorectal Cancer Colonic Diseases Colorectal Neoplasms Digestive System Diseases Digestive System Neoplasms Gastrointestinal Diseases Gastrointestinal Neoplasms Intestinal Diseases Intestinal Neoplasms Neoplasms Neoplasms by Site Rectal Diseases

Age range

20 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Samsung Medical Center

Seoul, South Korea

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

simvastatin

Drug

Primary outcomes

Progression free survival

Time frame: During treatment : up to 6weeks, off the treatment : up to 8weeks

Sponsors and collaborators

Lead sponsor

Samsung Medical Center

Other

Registry information

Important dates

Study start: 2013
Primary completion: 2017
Study completion: 2017
First posted: Jan 3, 2014
Registry last updated: Jan 17, 2018

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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Completed