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

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ClinicalTrials.gov Identifier: NCT01011478
Recruitment Status : Terminated
First Posted : November 11, 2009
Last Update Posted : April 11, 2016
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
NSABP Foundation Inc

Tracking Information
First Submitted Date  ICMJE November 10, 2009
First Posted Date  ICMJE November 11, 2009
Last Update Posted Date April 11, 2016
Study Start Date  ICMJE March 2010
Actual Primary Completion Date December 2014   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 7, 2014)
Occurrence of ≥ 1 adenomatous polyp of the colon or rectum, metachronous colorectal carcinoma, or colon cancer recurrence (APMC+R) [ Time Frame: From start of study through 5 years ]
Original Primary Outcome Measures  ICMJE
 (submitted: November 10, 2009)
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
Change History Complete list of historical versions of study NCT01011478 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: May 7, 2014)
  • Size, number, and features of colorectal adenomas, including advanced adenomas [ Time Frame: From start of study through 7 years ]
  • Disease -free survival [ Time Frame: Time from randomization to colon cancer recurrence,second primary cancer, or death from any cause through 7 years ]
  • Overall Survival: Time from randomization to death from any cause [ Time Frame: Time from randomization to death from any cause through 7 years ]
  • Recurrence-free interval: Time from randomization to first recurrence of colon cancer [ Time Frame: Time from randomization to first recurrence of colon cancer through 7 years ]
  • Second non-colorectal primary cancer-free interval [ Time Frame: Time from randomization to first occurrence of non-colorectal primary cancer through 7 years ]
  • Behavioral and Health Outcomes as measured by SF-12 component scores, global quality-of-life scale, and symptom checklist [ Time Frame: Assessed at 6, 12, 36, 60, and 84 months ]
  • Occurrence and grade of reported toxicities [ Time Frame: From start of study through 7 years ]
  • Measurements of relevant tumor and blood markers [ Time Frame: Samples collected at start of study ]
Original Secondary Outcome Measures  ICMJE
 (submitted: November 10, 2009)
  • Size, number, and features of colorectal adenomas
  • Time from randomization to first occurrence of APMC+R
  • Time from randomization to colon cancer recurrence, second primary cancer, or death from any cause
  • Time from randomization to death from any cause
  • Time from randomization to first recurrence of colon cancer
  • Time from randomization to first occurrence of non-colorectal primary cancer
  • SF-12 component scores, global quality-of-life scale, and symptom checklist
  • Occurrence and grade of reported toxicities
  • Measurements of relevant tumor and blood markers
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Rosuvastatin in Treating Patients With Stage I or Stage II Colon Cancer That Was Removed By Surgery
Official Title  ICMJE Statin Polyp Prevention Trial in Patients With Resected Colon Cancer
Brief 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.

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.

  • 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  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE
  • Colorectal Cancer
  • Precancerous Condition
Intervention  ICMJE
  • Drug: rosuvastatin
    Other Name: Crestor
  • Other: placebo
Study Arms  ICMJE
  • Placebo Comparator: Group 1: placebo
    Patients receive oral placebo once daily for 5 years.
    Intervention: Other: placebo
  • Experimental: Group 2: rosuvastatin
    Patients receive oral rosuvastatin once daily for 5 years.
    Intervention: Drug: rosuvastatin
Publications * Boman BM, Bandos H, Wickerham DL, et al.: Statin polyp prevention trial in patients with resected colon cancer: NSABP protocol P-5. [Abstract] J Clin Oncol 30 (Suppl 15): A-TPS1615, 2012.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: July 17, 2014)
406
Original Estimated Enrollment  ICMJE
 (submitted: November 10, 2009)
1740
Actual Study Completion Date  ICMJE February 2015
Actual Primary Completion Date December 2014   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria

  • Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
  • Patients must have the ability to swallow oral medication.
  • Patients must have resected adenocarcinoma of the colon staged as American Joint Committee on Cancer (AJCC) Stage 0, I, II, or III.
  • Patients must have had surgical resection of the colon adenocarcinoma with curative intent within 1 year prior to randomization. (Laparoscopically-assisted colectomy is permitted.)
  • Patients must have completed any adjuvant therapy prior to randomization.
  • Patients who are taking cardioprotective low-dose aspirin at study entry must not have clinically significant toxicity, as determined by the investigator, that precludes continuation of aspirin, and the patient must be willing to continue aspirin therapy (81 mg or 325 mg) throughout study therapy.
  • Colonoscopy requirements within 180 days prior to randomization:
  • The patient must have either undergone a preoperative or postoperative documented colonoscopy to the cecum (or small bowel anastomosis) with adequate bowel preparation.
  • All observed polyps must have been removed. (Polyps can be removed during colonoscopy or surgery performed prior to randomization.)
  • Postoperative serum creatinine performed within 90 days prior to randomization must be less than or equal to 1.5 x upper limit of normal (ULN) for the lab.
  • The following criteria for evidence of adequate hepatic function based on postoperative testing performed within 90 days prior to randomization must be met: aspartate aminotransferase (AST) or alanine aminotransferase (ALT) less than or equal to 3.0 x ULN for the lab, and Total bilirubin less than or equal to 1.5 x ULN for the lab

Exclusion Criteria

  • Tumor with the distal border located less than 12 cm from the anal verge.
  • Total colectomy or total proctocolectomy.
  • Classic Familial Adenomatous Polyposis, Attenuated Familial Adenomatous Polyposis (i.e., 20 or more adenomas, either synchronous or metachronous), or Hereditary Nonpolyposis Colorectal Cancer (Lynch Syndrome).
  • Malabsorption syndrome, ulcerative colitis, inflammatory bowel disease, resection of the stomach or small bowel, or other disease significantly affecting gastrointestinal function.
  • History of documented upper GI bleeding or upper GI ulcerative disease.
  • Statin use within 30 days prior to randomization.
  • Hyperlipidemia with clinical indication for statin therapy or other prescribed medication. Determination of acceptable fasting lipid values, within 90 days prior to randomization, should be in accordance with current dyslipidemia management guidelines.
  • Unwillingness to discontinue chronic use of nonsteroidal antiinflammatory drugs (NSAIDs) (other than cardioprotective low-dose aspirin 81 mg or 325 mg) prior to randomization.
  • Anticipated need for chronic use of NSAIDs (other than cardioprotective low-dose aspirin 81 mg or 325 mg).
  • Inadequately treated hypothyroidism, as determined by the investigator.
  • History of myopathy or rhabdomyolysis.
  • Hypersensitivity or intolerance to statins.
  • Chronic drug therapy with cyclosporine, coumarin anticoagulants, gemfibrozil, some other lipid-lowering therapies (fibrates or niacin), lopinavir/ritonavir, or drugs (such as ketoconazole, spironolactone, or cimetidine) that lower levels or activity of steroid hormones.
  • Pregnancy or lactation at the time of study entry. (Pregnancy testing must be performed within 14 days prior to randomization according to institutional standards for women of childbearing potential.)
  • Previous malignancies unless the patient has been disease-free for 5 or more years prior to randomization and is deemed by the physician to be at low risk for recurrence. Patients with the following cancers are eligible if diagnosed and treated within the past 5 years: all in situ cancers and basal cell and squamous cell carcinoma of the skin.
  • Other non-malignant systemic disease that would preclude a patient from receiving rosuvastatin or would prevent prolonged follow-up.
  • Administration of any investigational agent within 30 days before randomization.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Canada,   United States
Removed Location Countries Puerto Rico
 
Administrative Information
NCT Number  ICMJE NCT01011478
Other Study ID Numbers  ICMJE NSABP-P-5
NSABP P-5
NCI-2011-09183 ( Registry Identifier: CTRP (Clinical Trials Reporting Program) )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party NSABP Foundation Inc
Study Sponsor  ICMJE NSABP Foundation Inc
Collaborators  ICMJE National Cancer Institute (NCI)
Investigators  ICMJE
Principal Investigator: Norman Wolmark, MD NSABP Foundation Inc
PRS Account NSABP Foundation Inc
Verification Date April 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP