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
Study type: Interventional
Phase: Phase 2

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.
    

Detailed description: 
      This will be a single-center, phase-II, six-month-long, placebo-controlled, double blinded,
      randomized trial of the epidermal growth factor receptor (EGFR) inhibitor, erlotinib
      (Tarceva) and the cyclooxygenase (COX-2) inhibitor, sulindac in patients with familial
      adenomatous polyposis (FAP) or attenuated FAP. FAP is an autosomal dominant inherited colon
      cancer predisposition with a 100% risk of colon cancer in the absence of preventive care
      (endoscopy and surgery). Efficacious chemoprevention for duodenal adenomas is an unmet
      clinical need in FAP patients that would reduce the morbidity from duodenectomy and risk of
      duodenal adenocarcinoma. Currently the only Food and Drug Administration (FDA)-approved
      chemopreventive agent is celecoxib which results in a modest reduction of duodenal and
      colorectal polyps and is associated with cardiac toxicity at effective doses. If it can be
      shown that combinatorial inhibition of COX-2 and EGFR activity leads to successful regression
      in duodenal adenomatous polyps in FAP, it could be used as an effective chemopreventive
      regimen in FAP patients with duodenal adenomas or who have undergone surgical resection of
      duodenal adenomas or have many rectal adenomas. FAP and AFAP patients will be screened by
      endoscopy for presence of 5 or more duodenal polyps, then randomized to either A) erlotinib
      at 75 mg/day and sulindac at 150 mg/day or B) placebo for 6 months. The endpoint will be
      endoscopy at 6 months.

      Primary Aim : To determine if the combination of sulindac and erlotinib causes a significant
      regression of duodenal polyp burden at 6 mohths in FAP and attenuated FAP patients.

      Secondary Aim: To measure if combination of sulindac and erlotinib cause a reduction in total
      duodenal polyp count, and change in duodenal polyp burden or count stratified by genotype and
      initial polyp burden.
    

Intervention name(s): Erlotinib; Sulindac; Placebo A; Placebo B
Intervention type(s): Drug; Drug; Drug; Drug
Intervention description(s): 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).
Other intervention name(s): Tarceva (NDA#021743); Sulindac (ANDA#071891); Erlotinib placebo; Sulindac placebo
Intervention MeSH terms: Sulindac; Erlotinib Hydrochloride
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Prevention
Keywords: Familial Adenomatous Polyposis; Attenuated Familial Polyposis