Rosuvastatin in Treating Patients With Stage I or Stage II Colon Cancer That Was Removed By Surgery

This study is currently recruiting participants.
Verified February 2012 by National Cancer Institute (NCI)
Sponsor:
Collaborator:
Information provided by:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT01011478
First received: November 10, 2009
Last updated: February 9, 2012
Last verified: February 2012
  Purpose

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.


Condition Intervention Phase
Colorectal Cancer
Precancerous Condition
Drug: rosuvastatin
Other: placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Masking: Double-Blind
Primary Purpose: Treatment
Official Title: Statin Polyp Prevention Trial in Patients With Resected Colon Cancer

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Occurrence of ≥ 1 adenomatous polyp of the colon or rectum, metachronous colorectal carcinoma, or colon cancer recurrence (APMC+R) during a 5-year follow-up period [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Size, number, and features of colorectal adenomas, including advanced adenomas [ Designated as safety issue: No ]
  • Time from randomization to first occurrence of APMC+R [ Designated as safety issue: No ]
  • Time from randomization to colon cancer recurrence, second primary cancer, or death from any cause [ Designated as safety issue: No ]
  • Time from randomization to death from any cause [ Designated as safety issue: No ]
  • Time from randomization to first recurrence of colon cancer [ Designated as safety issue: No ]
  • Time from randomization to first occurrence of non-colorectal primary cancer [ Designated as safety issue: No ]
  • SF-12 component scores, global quality-of-life scale, and symptom checklist [ Designated as safety issue: No ]
  • Occurrence and grade of reported toxicities [ Designated as safety issue: Yes ]
  • Measurements of relevant tumor and blood markers [ Designated as safety issue: No ]

Estimated Enrollment: 1740
Study Start Date: March 2010
Estimated Primary Completion Date: January 2020 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I
Patients receive oral rosuvastatin once daily for 5 years.
Drug: rosuvastatin
Given orally
Placebo Comparator: Arm II
Patients receive oral placebo once daily for 5 years.
Other: placebo
Given orally

Detailed Description:

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01011478

  Show 554 Study Locations
Sponsors and Collaborators
National Surgical Adjuvant Breast and Bowel Project (NSABP)
Investigators
Study Chair: Bruce M. Boman, MD, PhD National Surgical Adjuvant Breast and Bowel Project (NSABP)
  More Information

Additional Information:
No publications provided

Responsible Party: Norman Wolmark, National Surgical Adjuvant Breast and Bowel Project
ClinicalTrials.gov Identifier: NCT01011478     History of Changes
Other Study ID Numbers: CDR0000658554, NSABP-P-5
Study First Received: November 10, 2009
Last Updated: February 9, 2012
Health Authority: Unspecified

Keywords provided by National Cancer Institute (NCI):
adenomatous polyp
stage I colon cancer
stage II colon cancer
adenocarcinoma of the colon

Additional relevant MeSH terms:
Colonic Neoplasms
Colonic Diseases
Colorectal Neoplasms
Precancerous Conditions
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Intestinal Diseases
Rectal Diseases
Rosuvastatin
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Anticholesteremic Agents
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Enzyme Inhibitors
Lipid Regulating Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on April 16, 2014