Simvastatin + Cetuximab/Irinotecan in K-ras Mutant Colorectal Cancer (CRC)

NCT01281761 | Completed Phase 2

• 1 other identifier: SMC IRB 2010-08-006
• Study Type: interventional
• Target: 52
• Locations: 1 country
• Sites: 1

Brief Summary

Based on the results from preclinical study, the investigators suggest that the addition of simvastatin at a dose of cardiovascular use (40 \~ 80 mg qd daily) may overcome cetuximab resistance in KRAS mutant colorectal cancer via B-Raf protein degradation and inducing Bim and Bad. Given the result of a phase II FOLFIRI plus cardiovascular dose of simvastatin (80mg qd daily) and this study, phase II study of conventional cetuximab treatment with 40 mg simvastatin is planned in metastatic colorectal cancer patients with KRAS mutation.

Conditions

Metastatic Colorectal Cancer

Outcome Measures

Primary Outcomes (1)

• response rate

  12 months

Study Arms (1)

cetuximab/irinotecan/simvastatin

EXPERIMENTAL

D1 Cetuximab 500mg/m2 IV stepwise shortened infusion duration- \[C1D1 over 120min, C2D1 over 90min,subsequent dose over 60min\] D1 Irinotecan 150-180mg/m2 + Dextrose 5% 500ml IV \[over 90min\] D1-14 Simvastatin 80mg P.O(continuous, daily) * every 2weeks

Drug: cetuximab/irinotecan/simvastatin

Interventions

cetuximab/irinotecan/simvastatin DRUG

D1 Cetuximab 500mg/m2 IV stepwise shortened infusion duration- \[C1D1 over 120min, C2D1 over 90min,subsequent dose over 60min\] D1 Irinotecan 150-180mg/m2 + Dextrose 5% 500ml IV \[over 90min\] D1-14 Simvastatin 80mg P.O(continuous, daily) every 2weeks

cetuximab/irinotecan/simvastatin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically-confirmed, advanced/metastatic colorectal carcinoma Failed both oxaliplatin and irinotecan based regimens for advanced/metastatic disease (last regimen has to be irinotecan-based chemotherapy; To be eligible, patients must also have received one of several qualifying, irinotecan regimens for at least 6 weeks and must have had documented progression of disease during receipt of this regimen or within six months thereafter.
• Ras mutation (+) (checked at the central lab)
• At least one measurable tumor mass according to RECIST 1.1
• Expected survival for approximately 12 weeks or longer
• Karnofsky Performance Score (KPS) ≥ 70
• Age ≥ 18 years
• WBC ≥ 3,500 cells/mm3 and ≤ 50,000 cells/mm3
• ANC ≥ 1,500 cells/mm3
• Hemoglobin ≥ 10 g/dL (transfusion allowed)
• Platelet count ≥ 100,000 plts/mm3
• Total bilirubin ≤ 1.5ULN
• AST, ALT ≤ 2.5 ULN (if liver metastases(+): AST,ALT ≤5.0 x ULN)
• Serum chemistries within normal limits (WNL) or Grade 1 (excluding alkaline phosphatase) - If patients are diabetic or have a screening random glucose \> 160 mg/dL, a fasting glucose must be done and patients must be WNL or Grade 1 in order to be eligible for the study.
• Written informed consent

You may not qualify if:

• Prior simvastatin therapy within 1-year from the date of study entry
• Severe or unstable cardiac disease, including (for example) coronary artery disease requiring increased doses of anti-anginal mediation and/or coronary angioplasty (including stent placement) within the preceding 24 months
• Current, known CNS malignancy (history of completely resected or irradiated brain metastases by WBRT or stereotactic radiosurgery allowed)
• Patients with CPK \> 5 x ULN at baseline
• Patients with alcohol abuse
• Uncontrolled hypothyroidism
• Concomitant use with clarithromycin, erythromycin, itraconazole, ketoconazole, nefazodone, telithromycin
• Concomitant use of gemfibrozil, cyclosporine, danazol, amiodarone, verapamil

Sponsors & Collaborators

• Samsung Medical Center: lead

Study Sites (1)

Samsung Medical Center

Seoul, 135-710, South Korea

Location

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Cetuximab

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Won Ki Kang, MD

  Samsung Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: January 20, 2011
• First Posted: January 24, 2011
• Study Start: November 1, 2010
• Primary Completion: September 1, 2012
• Study Completion: December 1, 2012
• Last Updated: June 14, 2013

Record last verified: 2013-06

Locations

KR (1)