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A Phase IIa Randomized, Double-Blind Trial of Erlotinib in Inhibiting EGF Receptor Signaling in Aberrant Crypt Foci of the Colon

Phase 2
18 Years
Open (Enrolling)
Adenomatous Polyp, Recurrent Colon Cancer, Recurrent Rectal Cancer, Stage I Colon Cancer, Stage I Rectal Cancer, Stage IIA Colon Cancer, Stage IIA Rectal Cancer, Stage IIB Colon Cancer, Stage IIB Rectal Cancer, Stage IIC Colon Cancer, Stage IIC Rectal Cancer, Stage IIIA Colon Cancer, Stage IIIA Rectal Cancer, Stage IIIB Colon Cancer, Stage IIIB Rectal Cancer, Stage IIIC Colon Cancer, Stage IIIC Rectal Cancer

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Trial Information

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
unacceptable toxicity.

After completion of study treatment, patients are followed up for 4 to 9 weeks.

Inclusion Criteria:

- Participants with one or more of the following criteria will be eligible to

- History of Stage I-III colorectal cancer, not treated in the past 6 months with
no anticipated treatment in the next 3 months

- Adenoma ≥ 1 cm in size

- 3 or more adenomas (of any size) removed at one colonoscopy within past 6 years

- Sessile serrated adenoma ≥ 5 mm in size

- Adenoma (of any size) with villous features (villous, tubulovillous)

- Adenoma (of any size) with high grade dysplasia

- Participants are eligible for randomization into the treatment phase of the trial if
they are found to have ≥ 4 ACFs at either baseline colonoscopy or baseline flexible

- Blood tests at screening which meet the following criteria:

- WBC > 3000/mm^3

- Platelets > 100,000/mm^3

- Hemoglobin > 10g/dl

- Plasma creatinine of < 1.6mg/dl

- Total bilirubin < 1.5 x the upper limit of normal

- Serum ALT < 1.5 x the upper limit of normal

- Serum AST < 1.5 x the upper limit of normal

- ECOG performance status 0-1

- Women of child-bearing potential and men taking study drug 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

- Ability to understand, as well as sign the written informed consent document

- If a woman is of child-bearing potential, she must have a negative pregnancy test
prior to study entry; should a woman become pregnant or suspect she is pregnant while
participating in this study, she should inform her study physician immediately

Exclusion Criteria:

- History of Inflammatory Bowel Disease (IBD)

- History of interstitial lung disease or chronic lung disease

- Smoking within the past 3 months

- Increased bleeding risk from rectal biopsy (Patients receiving aspirin or plavix can
be enrolled)

- Patients receiving warfarin or coumadin

- Uncontrollable diarrhea of any cause

- Patients, including rectal cancer patients, that have received prior radiation to the
rectum or pelvis

- Participants taking a known significant CYP 3A4 inducer or inhibitor; known
significant inducers/inhibitors include: amprenavir, aprepitant, atazanavir,
carbamazepine, clarithromycin, conivaptan, diltiazem, darunavir/ritonavir,
dronedarone, erythromycin, fluconazole, fosamprenavir, indinavir, itraconazole,
ketoconazole, nefazodone, nelfinavir, phenytoin, posaconazole, rifampin, ritonavir,
St. John's wort, saquinavir, telithromycin, tipranavir/ritonavir, verapamil,

- Women who are pregnant or breast-feeding

- Active keratoconjunctivitis, or corneal surgery in the past three weeks

- Any medical or psychosocial condition that could jeopardize the subject's
participation in and compliance to the study

- Participants who are taking any other investigational pharmaceutical agents

- Previous history of sensitivity to erlotinib, Iressa, or Erbitux, such as a rash that
is uncontrollable by topical steroids and/or antibiotics

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Prevention

Outcome Measure:

Change in ACF pERK levels

Outcome Description:

Quantification will be performed by Western blot analysis. Tested using paired t-test with a two-sided significance level of 0.05.

Outcome Time Frame:

From baseline to post-treatment (up to 30 days)

Safety Issue:


Principal Investigator

Timothy Morgan

Investigator Role:

Principal Investigator

Investigator Affiliation:

Chao Family Comprehensive Cancer Center


United States: Food and Drug Administration

Study ID:




Start Date:

July 2008

Completion Date:

September 2013

Related Keywords:

  • Adenomatous Polyp
  • Recurrent Colon Cancer
  • Recurrent Rectal Cancer
  • Stage I Colon Cancer
  • Stage I Rectal Cancer
  • Stage IIA Colon Cancer
  • Stage IIA Rectal Cancer
  • Stage IIB Colon Cancer
  • Stage IIB Rectal Cancer
  • Stage IIC Colon Cancer
  • Stage IIC Rectal Cancer
  • Stage IIIA Colon Cancer
  • Stage IIIA Rectal Cancer
  • Stage IIIB Colon Cancer
  • Stage IIIB Rectal Cancer
  • Stage IIIC Colon Cancer
  • Stage IIIC Rectal Cancer
  • Colonic Neoplasms
  • Rectal Neoplasms
  • Adenomatous Polyps



Chao Family Comprehensive Cancer Center Orange, California  92868