A Clinical Trial of COX and EGFR Inhibition in Familial Polyposis Patients
Condition: Adenomatous Polyposis Coli
MeSH terms: Colorectal Neoplasms; Nasopharyngeal Neoplasms; Adenomatous Polyposis Coli
Intervention: Erlotinib; Sulindac; Placebo A; Placebo B
Intervention description: Tarceva oral tablets are conventional, immediate-release tablets containing erlotinib as the hydrochloride salt. Erlotinib(75mg)will be taken once daily for six months in combination with sulindac.; Sulindac is a non-steroidal, anti-inflammatory indene derivative designed for the treatment of arthritic conditions. For this study, sulindac (150mg) will be taken twice daily in combination with erlotinib; Erlotinib (Tarceva) will provide a 25 mg identical placebo. This will be provided by the Division of Cancer Prevention at the NIH who will receive the drug and placebo from the manufacturer, OSI/Genentech. Dosage for Placebo A will be 75 mg a day for 6 months.; Sulindac will be encapsulated in 150 mg doses along with an identical encapsulated Placebo B. One 150 mg capsules of Placebo B will be taken twice per day with meals (breakfast and supper).
Intervention MeSH terms: Sulindac; Erlotinib Hydrochloride
Phase: Phase 2
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 92.0
Sex: All
Minimum age: 18 Years
Maximum age: 69 Years
Healthy volunteers: No
Keywords: Familial Adenomatous Polyposis; Attenuated Familial Polyposis

Summary:

      The purpose of this study is to determine in a randomized, placebo-controlled, phase II trial
      if the combination of sulindac and erlotinib causes a significant regression of duodenal and
      colorectal adenomas in familial adenomatous polyposis (FAP) and attenuated FAP (AFAP)
      patients.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients who are 18 years or older with a clinical or genetic diagnosis of FAP or
             attenuated FAP.

          -  Presence of duodenal polyps with a sum of diameters ≥ 5mm.

          -  Minimum of two weeks since any major surgery

          -  WHO performance status ≤1

          -  Adequate bone marrow function as show by: normal leukocyte count, platelet count ≥ 120
             x 109/L, Hgb > 12 g/dL

          -  Adequate liver function as shown by: normal serum bilirubin(≤ 1.5 Upper Limit Normal
             {ULN}) and serum transaminases (≤ 2.0 ULN)

          -  Patient must discontinue taking any Nonsteroidal anti-inflammatory drugs (NSAIDS)
             within one month of treatment initiation.

          -  Patients must be able to provide written informed consent.

        Exclusion Criteria:

          -  Prior treatment with any investigational drug within the preceding 4 weeks.

          -  Malignancies within the past 3 years except for adequately treated carcinoma of the
             cervix or basal or squamous cell carcinomas of the skins.

          -  Patients who have any severe and/or uncontrolled medical conditions or other
             conditions that could affect their participation in the study as determined by the
             Principal Investigator such as:

               1. Unstable angina pectoris, symptomatic congestive heart failure, myocardial
                  infarction ≤ 6 months prior to first study treatment, serious uncontrolled
                  cardiac arrhythmia

               2. Severely impaired lung function

               3. Any active (acute or chronic) or uncontrolled infection/ disorders.

               4. Nonmalignant medical illnesses that are uncontrolled or whose control may be
                  jeopardized by the treatment with the study therapy

               5. Liver disease such as cirrhosis, chronic active hepatitis or chronic persistent
                  hepatitis

          -  Screening clinical laboratory values that indicate any of the following:

               1. anemia

               2. thrombocytopenia

               3. leucopenia

               4. elevations of transaminases greater than 2X ULN

               5. elevation of bilirubin > 1.5 X ULN

               6. alkaline phosphatase elevation > 1.5 X ULN

               7. increased creatinine, urinary protein, or urinary casts outside the clinically
                  normal range.

          -  Gastrointestinal bleeding (symptoms including dyspnea, fatigue, angina, weakness,
             malaise, melena, hematochezia, hematemesis, anemia or abdominal pain will require
             clinical assessment to rule out gastrointestinal bleeding).

          -  Patient who is currently taking any anti-coagulation medication.

          -  Women who are pregnant or breast feeding.

          -  Patients with a known hypersensitivity to sulindac or erlotinib or to their excipients