A Phase IIa Randomized, Double-Blind Trial of Erlotinib in Inhibiting EGF Receptor Signaling in Aberrant Crypt Foci of the Colon
I. To test the hypothesis that erlotinib (erlotinib hydrochloride) doses as low as 25 mg
will decrease aberrant crypt foci (ACF) phosphorylated extracellular signal-regulated
kinases (pERK) levels from baseline (pre) to post erlotinib treatment.
I. To test the hypothesis that additional epidermal growth factor (EGF) inducible biomarkers
will decrease from baseline (pre) to post treatment with erlotinib 25 mg, 50 mg or 100 mg
orally (PO) once daily (QD) therapy.
II. To determine the mean decrease from baseline of the ACF: normal mucosa pERK ratio pre
and post 8-30 days of erlotinib.
III. To determine erlotinib concentration in plasma and colorectal tissue at 25 mg, 50 mg
and 100 mg doses after 8-30 days of therapy.
IV. To determine the incidence of rash, diarrhea and other side effects of low dose
OUTLINE: Patients are randomized to 1 of 3 treatment arms.
ARM I: Patients receive 100 mg of erlotinib hydrochloride PO and two 25 mg of placebo PO QD.
ARM II: Patients receive 50 mg of erlotinib hydrochloride PO and one 100 mg of placebo PO
ARM III: Patients receive 25 mg of erlotinib hydrochloride PO and one 100 mg of placebo and
one 25 mg of placebo PO QD.
In all arms, treatment continues for 8-30 days in the absence of disease progression or
After completion of study treatment, patients are followed up for 4 to 9 weeks.
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Prevention
Change in ACF pERK levels
Quantification will be performed by Western blot analysis. Tested using paired t-test with a two-sided significance level of 0.05.
From baseline to post-treatment (up to 30 days)
Chao Family Comprehensive Cancer Center
United States: Food and Drug Administration
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