Erlotinib Hydrochloride in Reducing Duodenal Polyp Burden in Patients With Familial Adenomatous Polyposis at Risk of Developing Colon Cancer
Condition: Attenuated Familial Adenomatous Polyposis; Familial Adenomatous Polyposis
MeSH terms: Colorectal Neoplasms; Nasopharyngeal Neoplasms; Adenomatous Polyposis Coli
Intervention: Erlotinib; Erlotinib Hydrochloride
Intervention description: Given PO; Given PO
Intervention MeSH terms: Erlotinib Hydrochloride
Phase: Phase 2
Study type: Interventional
Primary purpose: Prevention
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 46.0
Sex: All
Minimum age: 18 Years
Maximum age: 69 Years
Healthy volunteers: No

Summary:

      This phase II trial studies the side effects of erlotinib hydrochloride and how well it works
      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.
    

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