jueves, 4 de agosto de 2016

NCT01349881 Clinical Trial - National Cancer Institute

NCT01349881 Clinical Trial - National Cancer Institute
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National Cancer Institute

Eflornithine and/or Sulindac in Preventing Recurrence of High-Risk Adenomas and Second Primary Disease in Patients with Stage 0-III Colon or Rectal Cancer

Basic Trial Information

PhaseTypeStatusAgeTrial IDs
Phase IIIPreventionActive18 and overS0820
NCI-2012-02067, SWOG-S0820, NCT01349881

Trial Description


This randomized phase III trial studies how well eflornithine works compared to sulindac in preventing the return of the disease (recurrence) of high-risk adenomas and second primary disease in patients with stage 0-III colon or rectal cancer. Drugs used in chemotherapy, such as eflornithine and sulindac, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. It is not yet known whether eflornithine is more effective than sulindac when given alone or in combination in preventing recurrence of cancer.

Further Study Information

I. To assess whether eflornithine (+/- sulindac), sulindac (+/- eflornithine) or the combination are effective in reducing the three-year event rate (high-risk adenomas and second primary colorectal cancers) in patients with previously treated stage 0-III colon or rectal cancer.
I. To assess whether eflornithine, sulindac or the combination has efficacy against colorectal lesions with respect to high-grade dysplasia, adenomas with villous features, adenomas 1 cm or greater, multiple adenomas, any adenomas >= 0.3 cm, total advanced colorectal events, or total colorectal events.
II. To assess quantitative and qualitative toxicities of patients when treated with eflornithine, sulindac, or the combination compared to placebo.
III. To evaluate a minimal set of tagging single nucleotide polymorphisms across multiple genes relevant to eflornithine and sulindac, in order to characterize associations with decreased adenoma/second primary colorectal cancer (CRC) risk and adverse events.
IV. To examine the interaction of intervention arm and baseline statin use with respect to the 3-year event rate.
V. To examine the interaction of the intervention arm and patient-reported meat consumption with respect to the 3-year event rate.
VI. To perform population pharmacokinetic (PK) analysis of eflornithine and sulindac in patients with previously treated stage 0-III colon or rectal cancer.
OUTLINE: Patients are randomized to 1 of 4 treatment arms.
ARM I: Patients receive eflornithine placebo orally (PO) once daily (QD) and sulindac placebo PO QD for 36 months in the absence of disease progression or unacceptable toxicity.
ARM II: Patients receive eflornithine PO QD and sulindac placebo PO QD for 36 months in the absence of disease progression or unacceptable toxicity.
ARM III: Patients receive eflornithine placebo PO QD and sulindac PO QD for 36 months in the absence of disease progression or unacceptable toxicity.
ARM IV: Patients receive eflornithine PO QD and sulindac PO QD for 36 months in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up annually for 5 years.

Eligibility Criteria

Inclusion Criteria:
Patients with a primary colon or rectal cancer resection who are potentially eligible for S0820 may be pre-registered at Step 0; patients registered to Step 0 will appear on an institutional patient tracking report; patients registered to Step 0 are not registered to the S0820 protocol; to participate in S0820, patients must be registered to Step 1 after patient is consented and evaluation of eligibility; patients registered to S0820 at Step 0 continuing to Step 1 registration must use the same Southwest Oncology Group (SWOG) patient identification (ID) for registration to S0820 Step 1
Patients must have a history of stage 0, I, II or III colon or rectal adenocarcinoma that has been treated per standard care with resection alone or in combination with radiation or chemotherapy; adjuvant chemotherapy and radiation therapy (RT) treatment must have been completed at least 30 days prior to registration
Only patients with history of segmental resections are eligible (i.e. right colectomy, extended right colectomy, transverse colectomy, left colectomy, extended left colectomy, sigmoid colectomy, low anterior resection, abdominoperineal resection); the definition of resection does not include endomucosal resection (EMR); patients that have received total proctocolectomy are ineligible; for Tis (stage 0) or pT1 patients only, resection may consist entirely of polypectomy (without completion of partial colectomy) if ALL of the following criteria are met:
Single specimen, completely removed
Clear margins
None of the following must be present:
  • Moderate or poor differentiation
  • Lymphovascular invasion
  • Perineural invasion
Patients must be registered between 180 days and 465 days (inclusive) of primary resection; patients must show no evidence of disease (NED) based on post-operative colonoscopy (performed at least 180 days after the colon resection date or at least 120 days after the rectal resection date and prior to registration) and computed tomography (CT) scans* of chest, abdomen and pelvis (performed at least 180 days after the colon resection date or at least 120 days after the rectal resection date and prior to registration); patients with adenomas detected at the one-year postoperative colonoscopy are eligible if all adenomas have been completely removed
CT scan is for high risk patients, as per National Comprehensive Cancer Network (NCCN) guidelines and at the discretion of the treating physician
NOTE: magnetic resonance imaging (MRI) evaluation is an acceptable alternative to CT scans for eligibility purposes
Patients must not have cardiovascular risk factors including unstable angina, history of documented myocardial infarction or cerebrovascular accident, coronary artery bypass surgery, or New York Heart Association class III or IV heart failure; patients must not have known uncontrolled hyperlipidemia (defined as low-density lipoprotein cholesterol [LDL-C] >= 190 mg/dL or triglycerides >= 500 mg/dL) within the last 3 years prior to registration or uncontrolled high blood pressure (systolic blood pressure > 150 mm Hg) within 28 days prior to registration
Patients must not have a known history of familial adenomatous polyposis, hereditary nonpolyposis colorectal cancer, or inflammatory bowel disease
Patients must have a pure tone audiometry evaluation to document air conduction within 30 days prior to registration; patients with hearing loss > 40 dB in any of the five tested frequencies (250 Hertz [Hz], 500 Hz, 1,000 Hz, 2,000 Hz, 4,000 Hz) are not eligible; patients with active ear infections should be tested only after the acute phase of infection has resolved; for optimal results, it is recommended that testing be conducted by an audiologist, in a hearing test room, with insert earphones; Note: sites should not order audiometry evaluation until the potential participant has met all other eligibility criteria required for this study
Patients must not have known hypersensitivity to eflornithine or sulindac or the excipients byproducts; patients must not have experienced asthma, urticaria, or allergic-type reactions after taking aspirin or other non-steroidal antiinflammatory drugs (NSAIDs)
Patients must not have documented history of gastric/duodenal ulcer within the last 12 months; participant must not currently be on treatment for gastric/duodenal ulcer or be experiencing symptoms at study entry; patients with gastroesophageal reflux disease (GERD) are eligible, however, and these patients may receive over-the-counter histamine-2 (H2) antagonists; proton-pump inhibitors, or other prescription-based treatment for GERD
Patients must have a Zubrod performance status of 0-1
Patients must not be expecting to receive radiation or additional chemotherapy
Patients must not be receiving or plan to receive concomitant corticosteroids, nonsteroidal anti-inflammatory drugs (NSAIDs), nor anticoagulants on a regular or predictable intermittent basis; (NSAID use may not exceed 10 days per month); patients may receive daily aspirin for cardiovascular prophylaxis as long as acetylsalicylic acid (ASA) is =< 100 mg per day or =< two 325 mg tablets per week
Patients must have the ability to swallow oral medication
Patients must have no significant medical or psychiatric condition that would preclude study completion; tests and exams for this determination should be completed within 28 days prior to registration
Total white blood cells (WBC) >= 4.0 x 10^3/mcL
Platelets >= 100,000/mcL
Hemoglobin > 11.0 g/dL
Serum bilirubin =< 2.0 mg/dL
Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) or alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2 x IULN (institutional upper limit of normal)
Serum creatinine =< 1.5 x IULN obtained within 28 days prior to registration
No other prior malignancy is allowed except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or other cancer for which the patient has been disease-free for > 5 years
Patients must not be pregnant or nursing; women/men of reproductive potential must have agreed to use an effective contraceptive method; a woman is considered to be of "reproductive potential" if she has had menses at any time in the preceding 12 consecutive months; in addition to routine contraceptive methods, "effective contraception" also includes heterosexual celibacy and surgery intended to prevent pregnancy (or with a side-effect of pregnancy prevention) defined as a hysterectomy, bilateral oophorectomy or bilateral tubal ligation; however, if at any point a previously celibate patient chooses to become heterosexually active during the time period for use of contraceptive measures outlined in the protocol, he/she is responsible for beginning contraceptive measures
Patients must be offered the option to participate in submission of specimens for banking for future translational medicine studies
Patients participating through PK sites, must be offered the option to submit blood specimens for population pharmacokinetic analysis
Patients must be offered the option to participate in the Diet and Lifestyle Substudy
Individuals must not currently be participating in any other clinical trial for the treatment or prevention of cancer unless they are no longer receiving the intervention and are in the follow-up phase only; patients must also agree not to join such a trial while participating in this study
All patients must be informed of the investigational nature of this study and must sign and give written informed consent in accordance with institutional and federal guidelines
As part of the Oncology Patient Enrollment Network (OPEN) registration process the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system

Trial Contact Information

Trial Lead Organizations / Sponsors / Collaborators


  • National Cancer Institute
Charles David Blanke, Principal Investigator

Trial Sites

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