Rosuvastatin in the Treatment of Rectal Cancer

Official Title

Phase 2 Trial of Rosuvastatin (Crestor®) Combined With Standard Chemoradiation Therapy in the Treatment of High-Risk Locally Advanced Rectal Cancer

Summary:

This study will evaluate whether the addition of Rosuvastatin to standard chemoradiation therapy for the treatment of locally advanced rectal cancer may improve the pathological response rate and survival compared to standard chemoradiation therapy alone.

Trial Description

Primary Outcome:

• To determine the pathological complete response rate in patients with high-risk locally advanced rectal cancer treated with standard neo-adjuvant chemotherapy and radiation in combination with rosuvastatin.

Secondary Outcome:

• To determine the Ro resection rate
• To determine the pathological near-complete or complete tumour response rate
• To determine the sphincter preservation rate
• To determine the down staging rate
• To determine 3-year disease free survival
• To determine 3-year overall survival
• To determine the neoadjuvant rectal cancer (NAR) score
• Number of participants with treatment-related adverse events as assessed by CTCAE v4.0.
• To identify the genetic biomarkers that may be both prognostic and predictive of response and toxicity to treatment.
• To identify serological biomarkers that may be both prognostic and predictive of response and toxicity to treatment.
• To identify pathological biomarkers that may be both prognostic and predictive of response and toxicity to treatment.
• Tmax will be collected as pharmacokinetic data
• Cmax will be collected as pharmacokinetic data
• T1/2 will be collected as pharmacokinetic data
• Dose normalized Cmax will be collected as pharmacokinetic data
• Area under the curve (AUC) will be collected as pharmacokinetic data
• Dose normalized AUC will be collected as pharmacokinetic data

The standard treatment of locally advanced rectal cancer involves neoadjuvant chemoradiation therapy (CRT) followed by surgery and further adjuvant chemotherapy. The pathologic complete responses associated with neoadjuvant CRT are 10-20%. The prognosis of patients undergoing neoadjuvant CRT is associated to the extent of post-treatment tumour regression, the final primary tumour stage and presence of involved lymph nodes in the surgical specimen. This data suggests that treatments that enhance the pathological response may result in improvements in survival.

Overwhelming preclinical and clinical evidence suggests that statins demonstrate anticancer properties and sensitize cancer tissues and protects normal tissues to the effects of radiation. Hence, the investigators hypothesize that the addition of rosuvastatin to standard CRT for the treatment of locally advanced rectal cancer may improve the pathological response rate. This protocol describes an open-label single-arm phase 2 study designed to test this hypothesis. Moreover, this study will also identify genetic, serological, and pathological biomarkers that may be both prognostic and predictive of response and toxicity to treatment.

View this trial on ClinicalTrials.gov