RATIONALE: Rosuvastatin may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving rosuvastatin after surgery may kill any tumor cells that remain after surgery. It may also keep polyps from forming or colon cancer from coming back. It is not yet known whether rosuvastatin is more effective than a placebo in treating colon cancer that was removed by surgery. PURPOSE: This randomized phase III trial is studying rosuvastatin to see how well it works compared with placebo in treating patients with stage I or stage II colon cancer that was removed by surgery.
OBJECTIVES: Primary * To compare the effect of rosuvastatin vs placebo on the 5-year occurrence of adenomatous polyps of the colon or rectum, metachronous colorectal carcinoma, or colon cancer recurrence (APMC+R) in patients with resected stage I or II colon cancer. Secondary * To determine whether the effect of rosuvastatin vs placebo is of the same magnitude in patients taking aspirin (regardless of dose) compared to patients not taking aspirin. * To determine whether taking aspirin (regardless of dose) vs no aspirin will decrease the occurrence or APMC+R and, if there is an effect, to explore the relationship to dose. * To determine the effect of rosuvastatin in patients with familial colorectal cancer. * To determine the effect of rosuvastatin in patients with microsatellite unstable tumors (i.e., tumors displaying loss of MLH1 or MSH2 expression by IHC). * To determine the relationship between rosuvastatin therapy and features of colorectal adenomas as well as the size and number of colorectal adenomas. * To compare the time to APMC+R in patients treated with rosuvastatin vs placebo. * To compare the disease-free survival of patients treated with rosuvastatin vs placebo. * To compare the overall survival of patients treated with rosuvastatin vs placebo. * To compare the rate of recurrence of colon cancer in patients treated with rosuvastatin vs placebo. * To compare the rate of second non-colorectal primary cancers in patients treated with rosuvastatin vs placebo. * To determine the effect of rosuvastatin on health-related quality of life, global quality of life, and self-reported symptoms. * To compare the incidence and severity of adverse events associated with rosuvastatin vs placebo. * To assess relevant tumor and blood markers that may affect the metabolism, activity, or effect of the study drugs, such as HMG-CoA reductase, UGT1A6, P450-2C9, PTGS2 (COX-2), and other possible markers. OUTLINE: This is a multicenter study. Patients are stratified according to family history of a first-degree relative with colorectal cancer (yes vs no), intended aspirin dose (none vs 81 mg vs 325 mg), and adjuvant therapy for colon cancer (yes vs no). Patients are randomized to 1 of 2 treatment arms. * Group 1: Patients receive oral placebo once daily for 5 years. * Group 2: Patients receive oral rosuvastatin once daily for 5 years. Patients may complete a quality-of-life questionnaire at baseline and at 6, 12, 36, 60, and 84 months. Tumor tissue, serum, and blood samples may be collected periodically for biomarker and other analyses. After completion of study treatment, patients are followed up periodically for up to 2 years.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
406
Regional Medical Center
Anniston, Alabama, United States
Providence Cancer Center at Providence Hospital
Mobile, Alabama, United States
Hembree Mercy Cancer Center at St. Edward Mercy Medical Center
Fort Smith, Arkansas, United States
Arkansas Cancer Research Center at University of Arkansas for Medical Sciences
Little Rock, Arkansas, United States
Unnamed facility
Little Rock, Arkansas, United States
Occurrence of ≥ 1 Adenomatous Polyp of the Colon or Rectum, Metachronous Colorectal Carcinoma, or Colon Cancer Recurrence (APMC+R)
Percentage of patients with occurrence of APMC+R event. APMC+R events include at least one adenomatous polyp of the colon or rectum, metachronous colorectal carcinoma, or colon cancer recurrence
Time frame: Up to 4.8 years
Size of Colorectal Adenomas, Including Advanced Adenomas
The histologic size (diameter of adenoma into the wall of the colon; as per AJCC staging) of the largest adenoma among patients who have at least one adenoma detected. If histologic size was not available, the endoscopic size was provided.
Time frame: Up to 4.8 years
Disease-free Survival
Number of patients with DFS event (colon cancer recurrence, second primary cancer, or death from any cause)
Time frame: Up to 4.8 years
Overall Survival (OS)
Number of patients with the OS event (death from any cause)
Time frame: Up to 4.8 years
Recurrence-free Interval (RFI)
Number of patients with the RFI event (First recurrence of colon cancer)
Time frame: Up to 4.8 years
Second Non-colorectal Primary Cancer-free Interval
Number of patients with the first occurrence of non-colorectal primary cancer
Time frame: Up to 4.8 years
Behavioral and Health Outcomes as Measured by SF-12 Component Scores, Global Quality-of-life Scale, and Symptom Checklist
Global Quality-of-life Scale score, ranges from 0 (worst imaginable health status) to 10 (best imaginable health status.
Time frame: 12-month time point
Toxicity Assessed by Adverse Events
Percentage of patients with at least one grade 2 or higher adverse event reported.
Time frame: Up to 4.8 years
Measurements of Relevant Tumor and Blood Markers
This study terminated early. Data on samples was not collected, the relevant analyses were not performed.
Time frame: At randomization
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