s0820professional slidesversion 02 201409. s0820 a double blind placebo-controlled trial of...

S0820 Professional Slides Version 02 201409


S0820A double blind placebo-controlled trial of Eflornithine and Sulindac to prevent recurrence of high risk adenomas and second primary colorectal cancers in patients with Stage 0-III Colon Cancer, Phase III.


Jason A. Zell, D.O., M.P.H. (Medical Oncology)UC Irvine Medical Center

Powel H. Brown, M.D., Ph.D. (Medical Oncology)M.D. Anderson Cancer Center

Study Coordinators


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 cancer.

Primary Objective


U.S. Cancer statistics, 2013

CA: A Cancer Journal for CliniciansVolume 63, Issue 1, pages 11-30, 17 JAN 2013 DOI: 10.3322/caac.21166http://onlinelibrary.wiley.com/doi/10.3322/caac.21166/full#fig1

http://onlinelibrary.wiley.com/doi/10.3322/caac.v63.1/issuetoc

http://onlinelibrary.wiley.com/doi/10.3322/caac.21166/full#fig1


Colorectal Cancer

• Primary Prevention: Screening and early detection result in 5-year survival rates of 90% (colon) and 80% (rectum) for localized disease

• The problem: 50-60% receive proper screening, and 60% present with advanced stage disease

• Result: overall survival is 64%*5-

year

Sur

viva

l (%

)

Survival Estimates

Siegal, R, Ca-A Cancer Journal for Clinicians 2013; 63 (1):11-30.


Second Primary Colorectal Cancersamong Stage I-III CRC cases

• Occur in ~1-4% of treated CRC patients

• Among 69,809 colon cancer cases in California 1990-2005, 40% increased risk of 2nd primary CRC among CRC cases compared to the underlying population at risk*

• Standardized Incidence Ratio = 1.4 (95% CI 1.3-1.5)

* Raj, KP, et al. Risk of second primary colorectal cancer among colorectal cancer cases: A population-based analysis. J Carcinogenesis 2011;10:6


Accrual Targets

Ethnic Category Sex/GenderFemales Males Total

Hispanic or Latino 32 + 44 76

Not Hispanic or Latino 608 + 804 1,412

Ethnic Category: Total of all subjects 640 + 848 = 1,488

Racial Category

American Indian or Alaskan Native 9 + 13 = 22

Asian 19 + 26 = 45

Black or African American 51 + 68 = 119

Native Hawaiian or other Pacific Islander 9 + 13 = 22

White 552 + 728 = 1,280

Racial Category: Total of all subjects 640 + 848 = 1,488


REGISTER

S TRA T I F Y*

RANDOMIZE

eflornithine + sulindac placebo

(n=335)

eflornithine placebo + sulindac (n=335)

eflornithine + sulindac (n=335)

eflornithine placebo + sulindac placebo

(n=335)

3-year study

interventionColonoscopy

Primary endpoint = 3-year rate of

high risk adenomas

or 2nd primary CRCs.

End-of-study audiogram,

blood collection

S0820 Study Design: (n=1488)

Baseline data collection, audiogram, blood, CT-scans, & colonoscopy at Year-1 post resection

*Stratification by stage

FOL LOW-UP

5-year follow-up

Activated: March 1, 2013


Study Drug Information Eflornithine (DFMO) or Placebo, 250 mg, 2 tablets oral daily x 3 years

Sulindac (NSAID) or Placebo, 150 mg, 1 tablet oral daily x 3 years

~1,488 volunteers assigned randomly to one of four trial arms

take 2 take 1

Arm 1 placebo placebo

Arm 2 eflornithine placebo

Arm 3 placebo sulindac

Arm 4 eflornithine sulindac


Cardiovascular Risk AmendedAs of May 1, 2014, the protocol was amended to define specific cardiovascular risk factors and specific blood pressure parameters for eligibility. Patients must NOT have:- uncontrolled high blood pressure- unstable angina- history of documented myocardial infarction- history of document cerebrovascular accident- Class III or IV heart failure as defined by the NY Heart Association- known uncontrolled hyperlipidemia within last 3 years


• Stage 0, I, II or III colon adenocarcinoma treated per standard care with resection alone or in combination with adjuvant chemotherapy

• Adjuvant chemotherapy must have been completed at least 30 days prior to registration

• Patients with rectosigmoid cancers are eligible only if their treatment did NOT involve radiation therapy (i.e. neo-adjuvant or adjuvant radiation) (mid-low rectal cancers are not eligible)

• Patients must be registered between 274 days and 465 days (inclusive) of primary resection

Eligibility


• CT scan performed at least 180 days after colon resection• Must be at least 18 years of age & no history of familial

adenomatous polyposis, hereditary nonpolyposis colorectal cancer, or inflammatory bowel disease

• Must have a pure tone audiometry evaluation to document air conduction• Not be expecting to receive radiation or additional

chemotherapy• Not be receiving or plan to receive concomitant

corticosteroids NSAIDs, nor anticoagulants on a regular or predictable intermittent basis

• Patients must have adequate blood counts

Eligibility (continued)


• Year 1: H & P, CBC & chemistries every 3 months• Year 2 & 3: H & P, CBC & chemistries every 6 months• PE & chemistries, colonoscopy & pure tone audiogram 3 years

after randomization• Patients followed annually for 5 years (after completion of 3

years of intervention):• H & P• Weight and Performance Status• Follow-up colonoscopy at 8 years post-registration per NCCN

guidelines

Follow-up


• Study drug adherence measured by returned tablet count• Unused medication returned to the clinic at each visit• Patients document study drug intake on an Intake Calendar• Individualized adherence strategies used if adherence is ↓75%:

• Communicate with patient to define barriers• Review patient’s routine for taking study drugs• Seek family assistance• Consider more frequent contact with patient using phone check-in

Adherence


• 3-year event rate after registration among Stage 0-III colon cancer patients• Event = high risk adenoma or 2nd primary colorectal

cancer• High risk adenoma = either advanced adenoma (villous or tubulovillous histology, size ≥ 1 cm, or high grade dysplasia) or multiple adenomas (3 or more each > 0.3 cm)

Primary Endpoint


• Total advanced colorectal event rate• Recurrence• High-grade dysplasia• Adenomas with villous features• Adenomas ≥ 1 cm• Multiple adenomas• Adenoma• Total colorectal event rate• Time to first clinically apparent high-risk adenoma or 2nd

primary colorectal cancer

Secondary Endpoints


• Submission of blood specimen for nutritional assays and banking:• including genotyping and biochemical assays• fasting whole blood sample required after registration and prior

to beginning treatment

• Diet and Lifestyle Substudy:• completion of Diet & Lifestyle Questionnaires after registration

Optional for patients…….


Pharmacokinetic StudyALL SITES have the option to participate in the population pharmacokinetic sampling:• Sampling occurs twice at 3 & 12 months during morning visits• Collected only on patients receiving intervention at 3 & 12

months• Kits are ordered from Cancer Prevention Pharmaceuticals, Inc. Interested sites should contact:

Patricia O’Kane [email protected] Operations Office

San Antonio, TX

mailto:[email protected]


Please help identify potential patientsHistory of stage 0, I, II or III colon adenocarcinomaTreated with resection alone or in combination with adjuvant

chemotherapyNED at one year post-operative assessment

Timing: Patients must be registered between 274 and 465 days (inclusive) of primary

resection Colonoscopy and CT scans of chest, abdomen and pelvis NED performed at least 274

days after resection date and prior to registration Polyps detected at colonoscopy must be completely removed

Adjuvant chemo completed ≥ 30 days prior to registration CT Scan is for high risk patients per NCCN guidelines & at discretion of treating

physician


Materials for the Investigators and Staff include:• Webinar• FAQs• Pocket Protocol

Recruitment Materials available:• Printable Brochure• Promotional Flyers• Strategies

• Professional Slide Set• Promotional Letter to Physicians• Study Logo and Printing Instructions

• Thank You letter to Referring Physicians• Adherence Strategies

Materials for the patient include:• Thank You Letter from the PI for Enrolling• List of Resources

S0820 Web Page


S0820

Thank You

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