3/10/2017 Protocol Updates Added - PowerPoint Presentation

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3/10/2017

Protocol Updates Added

Updated March 2017

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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 or rectal cancer, Phase III.

3/10/2017Protocol Updates Added

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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 CenterStudy Coordinators

3/10/2017Protocol Updates Added

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Assess whether the combination of eflornithine and sulindac is 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.

Primary Objective

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Protocol Updates Added

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U.S. Cancer statistics,

2017

CA: A Cancer Journal for Clinicians

Volume 67, Issue 1,

pages 7-30, 5 JAN 2017 DOI: 10.3322/caac.21387

http://onlinelibrary.wiley.com/doi/10.3322/caac.21387/full#caac21387-fig-0001

3/10/2017

Protocol Updates Added

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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 Survival (%)

Survival Estimates

Siegal, R,

Ca-A Cancer Journal for Clinicians

2013; 63 (1):11-30.

3/10/2017

Protocol Updates Added

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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 2

nd 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

3/10/2017

Protocol Updates Added

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3/10/2017Protocol Updates Added

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REGISTER

S TRA T I F Y

*

RANDOMIZE

eflornithine + sulindac placebo (

n=189)

eflornithine placebo + sulindac

(n=25) Closed to further accrual, effective w/A#2

eflornithine +

sulindac

(

n=25) Closed to further accrual, effective w/A#2

eflornithine placebo + sulindac placebo (

n=189)

3-year study intervention

Colonoscopy

Primary endpoint = 3-year rate of high risk adenomas or 2

nd

primary CRCs.

End-of-study audiogram, blood collection

S0820 Study Design: (

n=428)

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

Protocol updates added 3/7/2017

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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

 

Under the new study design, ~480

volunteers will be assigned randomly to one of

two

trial arms

 

take 2

take 1

 

Arm 1

placebo

placebo

(Closed) Arm 2

eflornithine

placebo

(Closed)

Arm

3

placebo

sulindac

Arm 4

eflornithine

sulindac

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Protocol Updates Added

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Patients must not have:Unstable anginaHistory of documented myocardial infarction, CVA. Or coronary artery bypass surgery or New York Heart Association Class III or IV heart failure

Known uncontrolled hyperlipidemia within last 3 years prior to registrationUncontrolled high blood pressure within 28 days prior to registration

Cardiovascular Risk

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Protocol Updates Added

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Stage 0, I, II or III colon or rectal cancer 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)Had a primary resection one year previously and had a one-year post-op

colonoscopy and CT scans of chest, abdomen and pelvis showing no evidence of disease.

Eligibility

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Must be at least 18 years of ageNo 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 chemotherapyNot be receiving or plan to receive concomitant corticosteroids NSAIDs, nor anticoagulants on a regular or predictable intermittent basisPatients must have adequate blood counts

Eligibility (continued)

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Protocol Updates Added

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Patients will be randomized using a two arm binomial design3/10/2017

Protocol Updates Added

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Year 1: H & P, CBC & chemistries every 3 monthsYear 2 & 3: H & P, CBC & chemistries every 6 monthsColonoscopy & audiogram 3 years after randomizationPatients followed annually for 5 years (after completion of 3 years of intervention):H & P

Weight and Performance StatusFollow-up colonoscopy at 8 years post-registration per NCCN guidelines

Follow-up3/10/2017

Protocol Updates Added

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Protocol Updates Added

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Study drug adherence measured by returned tablet countUnused medication returned to the clinic at each visitPatients document study drug intake on an Intake CalendarIndividualized adherence strategies used if adherence is ↓75%:

Communicate with patient to define barriersReview patient’s routine for taking study drugsSeek family assistanceConsider more frequent contact with patient using phone check-in

Adherence3/10/2017

Protocol Updates Added

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3-year event rate after registration among Stage 0-III colorectal cancer

patientsEvent = high risk adenoma or 2nd primary colorectal cancerHigh 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

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Protocol Updates Added

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Total advanced colorectal event rateRecurrenceHigh-grade dysplasiaAdenomas with villous featuresAdenomas ≥ 1 cmMultiple adenomas

AdenomaTotal colorectal event rateTime to first clinically apparent high-risk adenoma or 2nd primary colorectal cancerSecondary Endpoints

3/10/2017Protocol Updates Added

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Submission of blood specimen for nutritional assays and banking:including genotyping and biochemical assaysfasting whole blood sample

required after registration and prior to beginning treatmentDiet and Lifestyle Substudy:completion of Diet & Lifestyle Questionnaires after registration

Optional for patients…….

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Protocol Updates Added

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Please help identify potential patients

History of stage 0, I, II or III colon or rectal adenocarcinoma

Treated with resection alone or in combination with adjuvant chemotherapyNED at one year post-operative assessment

Timing:

Patients must be registered

between 180 days and 456 days (inclusive) of primary colon resection or at least 120 days after rectal 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

and RT treatment

completed

≥ 30 days prior to registration

CT Scan is for high risk patients per NCCN guidelines & at discretion of treating physician

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Protocol Updates Added

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Materials for the Investigators and Staff include:FAQs Protocol Card

Recruitment Materials available:

Patient BrochurePromotional Flyer

Professional Slide Set

Promotional Letter to

Physicians

Notification of Registration

letter

Adherence Strategies

Materials for the patient include:

Thank You Letter from the

PI

List of

Resources & Advocates Contacts

Printable birthday cards

S0820 Web Page

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Protocol Updates Added

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S0820Thank You

3/10/2017Protocol Updates Added