Basic Trial Information
Trial Description
     Summary
     Further Trial Information
     Eligibility Criteria
Trial Contact Information

Basic Trial Information

Trial Description

Summary

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.

Further Study Information

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.

• Arm I: Patients receive oral rosuvastatin once daily for 5 years.

• Arm II: Patients receive oral placebo 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.

Eligibility Criteria

DISEASE CHARACTERISTICS:

• Has undergone complete resection of stage I or II adenocarcinoma of the colon with curative intent within the past year

• Laparoscopically-assisted colectomy is allowed

• Completed adjuvant therapy (if indicated)

• Has undergone either a preoperative or postoperative colonoscopy to the cecum (or small bowel anastomosis) with adequate bowel preparation within the past 180 days

• All observed polyps must have been removed

• Polyps can be removed during colonoscopy or surgery performed prior to randomization

• Distal border of the tumor located ≥ 12 cm from the anal verge

• No classic familial adenomatous polyposis, attenuated familial adenomatous polyposis (i.e., ≥ 20 adenomas, either synchronous or metachronous), or hereditary nonpolyposis colorectal cancer (Lynch syndrome)

PATIENT CHARACTERISTICS:

• ECOG performance status 0-1

• Postoperative serum creatinine ≤ 1.5 times upper limit of normal (ULN)

• AST and/or ALT ≤ 3.0 times ULN

• Total bilirubin ≤ 1.5 times ULN

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception during and for ≥ 3 months after completion of study treatment

• Able to swallow oral medication

• No malabsorption syndrome, ulcerative colitis, inflammatory bowel disease, resection of the stomach or small bowel, or other disease significantly affecting gastrointestinal (GI) function

• No history of documented upper GI bleeding or upper GI ulcerative disease

• No hyperlipidemia with clinical indication for statin therapy or other prescribed medication (determination of acceptable fasting lipid values should be in accordance with current dyslipidemia management guidelines)

• No inadequately treated hypothyroidism, as determined by the investigator

• No history of myopathy or rhabdomyolysis

• No other malignancy within the past 5 years except for in situ cancers or basal cell or squamous cell carcinoma of the skin

• Deemed by the physician to be at low risk for recurrence

• No hypersensitivity or intolerance to statins

• No other non-malignant systemic disease that would preclude rosuvastatin administration or prolonged follow-up

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics

• More than 30 days since prior statins

• More than 30 days since prior investigational agents

• No prior total colectomy or total proctocolectomy

• No concurrent chronic use of NSAIDs

• Concurrent cardioprotective low-dose aspirin allowed provided there is no clinically significant toxicity, as determined by the investigator, that would preclude continuation of aspirin AND patient is willing to continue the same dose (81 mg or 325 mg) throughout study therapy

• No concurrent chronic drug therapy with cyclosporine, coumarin anticoagulants, gemfibrozil, other lipid-lowering therapies (e.g., fibrates or niacin), lopinavir/ritonavir, or drugs (e.g., ketoconazole, spironolactone, or cimetidine) that lower levels or activity of steroid hormones

Trial Contact Information

Trial Lead Organizations/Sponsors

National Surgical Adjuvant Breast and Bowel Project

Bruce M. Boman

Study Chair

U.S.A.
Pennsylvania
	Pittsburgh
	National Surgical Adjuvant Breast and Bowel Project
		Bruce M. Boman
			Email: bruce.boman@nsabp.org

Link to the current ClinicalTrials.gov record.
NLM Identifer NCT01011478
Information obtained from ClinicalTrials.gov on November 20, 2012