The following datasets contain the data available for EPPT MAY2016-07-01. The description and documentation for each file is listed below. SAS7bdat and CSV versions of the actual data will be available to CDAS projects approved to use this study's data.

Analysis Datasets

Raw Datasets

These 38 datasets contain the raw form data received, excluding PII.

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Trial Summary

This phase II trial studied the side effects of taking Erlotinib hydrochloride once a week for 6 months and how well it worked in reducing duodenal polyp burden in patients with familial adenomatous polyposis at risk of developing colon cancer. Erlotinib hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

All patients received Erlotinib 350 mg per week for 6 months.

Target Enrollment: 70

Actual Enrollment: 46

Enrollment Statistics

Actual Registration: 76

• 76 were evaluated for eligibility
  • 30 were excluded for not meeting inclusion/exclusion criteria
  • 46 were registered for 6 months of intervention
    • 42 completed study
    • 4 withdrew due to adverse events

• Age
  • Mean: 44.1
  • Median: 42
  • Range: 18-68
• Sex
  • Female: 22 (47.8%)
  • Male: 24 (52.2%)
• BMI
  • Mean: 29.0
  • Median: 83.4
  • Range: 19.8-59.2

Eligibility Criteria

Inclusion Criteria

• Pre-Registration Inclusion:
  • Diagnosis of familial adenomatous polyposis (FAP) or attenuated familial adenomatous polyposis (AFAP), defined as at least one of the following:
    • Genetic diagnosis with confirmed APC mutation (Clinical Laboratory Improvement Act [CLIA] certified lab or research testing)
    • Obligate carrier
    • Clinical diagnosis of classic FAP with >= 100 colorectal adenomas status post colectomy and a family history of FAP
    • Clinical diagnosis of FAP, based on personal and family history; Note: This criterion requires documented review and agreement from either the study chair or the Cancer Prevention Network (CPN) lead investigator
  • Ability to understand and the willingness to sign a written informed consent document
  • Willing to discontinue taking nonsteroidal anti-inflammatory drugs (NSAIDS) for 30 days prior to initiation of and during intervention; exception: use of =< 81 mg daily or =< 650 mg weekly aspirin is allowed
  • Willing to discontinue smoking for the duration of study intervention
  • Willing to provide mandatory biospecimens as specified in the protocol
• Registration Inclusion:
  • Eastern Cooperative Oncology Group (ECOG) performance status =< 1
  • Leukocytes (white blood cells [WBC]) >= 3,000/uL (>= 2,500/uL for African-American participants)
  • Platelet count >= 100 x 10^9/L
  • Hemoglobin >= 11.5 g/dL
  • Total bilirubin =< 1.5 x institutional upper limit of normal (ULN)
  • Alkaline phosphatase =< 1.5 x institutional upper limit of normal (ULN)
  • Aspartate aminotransferase (AST)/serum glutamic-oxaloacetic transaminase (SGOT) =< 2 x institutional upper limit of normal (ULN)
  • Alanine aminotransferase (ALT)/serum glutamate pyruvate transaminase (SGPT) =< 2 x institutional upper limit of normal (ULN)
  • Creatinine =< institutional upper limits of normal (ULN)
  • Urinary testing results within institutional limits of normal or deemed clinically insignificant
  • Spigelman 2-3
  • Not pregnant or breast feeding; Note: the effects of erlotinib (Tarceva) on the developing human fetus at the recommended therapeutic dose are unknown; for this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her study physician immediately; breastfeeding should be discontinued if the mother is treated with erlotinib
  • Willing to use adequate contraception to avoid pregnancy or impregnation until 2 weeks after discontinuing study agent

Exclusion Criteria

• Pre-Registration Exclusion:
  • Any prior treatment with erlotinib or other agent whose primary mechanism of action is known to inhibit EGFR
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to erlotinib
  • Use of potent CYP3A4 inhibitors, including but not limited to ketoconazole, atazanavir, clarithromycin, indinavir, itraconazole, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, troleandomycin, voriconazole, and grapefruit or grapefruit juice
  • Use of potent CYP3A4 inducers, including but not limited to rifampicin, rifabutin, rifapentine, phenytoin, carbamazepine, phenobarbital, and St. John's wort
  • Use of any other investigational agents =< 12 weeks prior to pre-registration
  • Uncontrolled intercurrent illness or recent surgical procedure that in the opinion of the investigative team would limit compliance with study requirements, including, but not limited to:
    • Ongoing or active infection
    • Symptomatic congestive heart failure
    • Myocardial infarction =< 6 months prior to intervention
    • Severely impaired lung function
    • Nonmalignant medical illnesses that are uncontrolled or whose control may be jeopardized by the treatment with study intervention
    • Diagnosed liver disease, such as cirrhosis, chronic active hepatitis, or chronic persistent hepatitis
    • Unstable angina pectoris
    • Cardiac arrhythmia
    • Psychiatric illness/social situations
  • History of invasive malignancy =< 3 years prior to pre-registration; exception: adequately treated carcinoma of the cervix, carcinoma in situ, or basal or squamous cell carcinomas of the skin
  • Individuals on anticoagulation medications who cannot safely discontinue the medication for at least 48 hours prior to the study endoscopy, as determined by the study investigator and/or participant's primary healthcare provider
  • History of any upper gastrointestinal (GI) surgery that does not permit access to or evaluation of a 10 cm segment of the duodenum that includes the duodenal bulb, i.e. Whipple procedure or similar
• Registration Exclusion:
  • Histologically-confirmed high grade dysplasia (HGD), cancer, or polyp burden that is not quantifiable
  • Regular (>= 2 times per week) use of drugs that alter the pH of the gastrointestinal tract (GI) tract, such as proton pump inhibitors (PPI) and antacids; exceptions: individuals who use prescription PPIs and have approval from their primary health care provider to replace the PPI with an H2 receptor agonist, i.e. ranitidine, for the duration of the trial will be eligible
  • Gastrointestinal bleeding; note that the presence of any symptoms (dyspnea, fatigue, angina, weakness, malaise, melena, hematochezia, hematemesis, anemia, abdominal pain) will require clinical assessment to rule out gastrointestinal bleeding

The Schema is a timeline of the study. It indicates start/end points, visits expected, major testing to be done, and any other information that is crucial to understanding how the study was completed.

Over the course of this study 2,990 biospecimens were collected. Research blood kits were provided by BAP Kit Building (Biospecimen Accessioning and Processing Core Facility) and were used for collecting and shipping all research samples for analysis. Optional blood and urine specimens were collected at baseline, Month 3, and the end of the study (Month 6). The blood specimens were processed into serum, plasma, and buffy coat samples. Tissue endoscopic biopsies were collected at baseline and Month 6.

Utilizing the BAP kit, urine was collected into a dedicated urine container and then aliquoted to tubes. These tubes were then shipped to BAP on dry ice.

Blood samples were collected into a 10 mL no additive red-topped tube and a 10 mL purple topped tube or just 2 10 mL purple topped tubes. The red-top tube was processed into serum while the purple-topped tube was processed into plasma and buffy coat specimens. These specimens were then shipped to BAP on dry ice.

Different number of tissue samples were taken depending on the Spigelman score. At baseline, at least one polyp will be removed and used for eligibility and Spigelman stage determination. If Spigelman 2, 4 biopsies of normal duodenal mucosa and 1 biopsy of duodenal polyp will be taken. If Spigelman 3, 4 biopsies of normal duodenal mucosa and 2 biopsies of duodenal polyps will be taken. If rectal stump or intact rectum then just 4 biopsies of normal rectal mucosa will be taken. One rectal mucosa and if applicable one polyp will be placed int RNA later and refrigerated at 4-6°C or snap frozen. The rest of the samples will be placed in separate cryovials and snap frozen in liquid nitrogen before being shipped to BAP.

1. Participants could either have serum and plasma/buffy coat or could have 2 samples of plasma and buffy coat
2. Depending on Spigelman score, participants could have different numbers of biopsies. All participants had 4 duodenal mucosa biopsies. If they had a Spigelman 2 score then they had a duodenal polyp biopsy. If they had a Spigelman 3 score then they had 2 duodenal polyp biopsies.

Results/Findings:

Forty-six participants (mean age, 44.1 years (range, 18–68); women, 22 (48%)) were enrolled; 42 participants completed 6 months of intervention and were included in the per-protocol analysis. Duodenal polyp burden was significantly reduced after 6 months of weekly erlotinib intervention, with a mean per cent change of −29.6% (95% CI, −39.6% to −19.7%; p<0.0001). Similar results were observed in subgroup analyses defined by participants with advanced duodenal polyposis (Spigelman 3) at baseline (mean, −27%; 95% CI, −38.7% to −15.2%; p<0.0001). Post-intervention Spigelman stage was downstaged in 12% of the participants. Lower GI polyp number was also decreased after 6 months of intervention (median, −30.8%; IQR, −47.4% to 0.0%; p=0.0256). Grade 2 or 3 AEs were reported in 71.7% of subjects, with only two experiencing grade 3 toxicity at least possibly related to intervention.