Erlotinib Hydrochloride in Treating Patients With Stage I-III Colorectal Cancer or Adenoma

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00754494
First received: September 17, 2008
Last updated: February 7, 2013
Last verified: February 2013

September 17, 2008
February 7, 2013
July 2008
October 2012   (final data collection date for primary outcome measure)
Change in ACF pERK levels [ Time Frame: From baseline to post-treatment (up to 30 days) ] [ Designated as safety issue: No ]
Quantification will be performed by Western blot analysis. Tested using paired t-test with a two-sided significance level of 0.05.
Comparison of decrease in aberrant crypt foci (ACF) pERK levels [ Designated as safety issue: No ]
Complete list of historical versions of study NCT00754494 on ClinicalTrials.gov Archive Site
  • Change in EGF-inducible markers [ Time Frame: From baseline to post-treatment (up to 30 days) ] [ Designated as safety issue: No ]
    These include phosphorylated ERBB2, phosphorylated AKT, total EGFR, Ki-67 and Cyclin D1. Quantification will be performed by Western blot analysis. Tested using a paired t-test with a two-sided significance level of 0.05.
  • ACF: normal mucosa pERK ratio [ Time Frame: Up to day 30 ] [ Designated as safety issue: No ]
    Quantification will be performed by Western blot analysis. Tested using analysis of variance with subsequent pairwise comparisons using the Tukey method to adjust for multiple comparisons.
  • Erlotinib hydrochloride concentration in plasma and colorectal tissue [ Time Frame: Up to day 30 ] [ Designated as safety issue: No ]
    Will be quantified in biopsy samples using appropriate descriptive statistics (means and standard deviations).
  • Side effect profile for low dose erlotinib hydrochloride [ Time Frame: Up to 9 weeks ] [ Designated as safety issue: Yes ]
    Described for each arm using frequencies and percents.
  • Change over time for EGF-inducible markers (i.e., pERBB2, pAKT, total EGFR, Ki-67, and cyclin D1) [ Designated as safety issue: No ]
  • Pre- vs post-treatment ACF/normal mucosa pERK ratio [ Designated as safety issue: No ]
  • Erlotinib hydrochloride concentration in plasma and colorectal tissue [ Designated as safety issue: No ]
  • Treatment-related side effects [ Designated as safety issue: Yes ]
Not Provided
Not Provided
 
Erlotinib Hydrochloride in Treating Patients With Stage I-III Colorectal Cancer or Adenoma
A Phase IIa Randomized, Double-Blind Trial of Erlotinib in Inhibiting EGF Receptor Signaling in Aberrant Crypt Foci of the Colon

This randomized phase II trial is studying how well erlotinib hydrochloride works in treating patients with stage I-III colorectal cancer or adenoma. Erlotinib hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. Erlotinib hydrochloride may also stop tumors from growing or coming back

PRIMARY OBJECTIVES:

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.

SECONDARY OBJECTIVES:

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 erlotinib.

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 QD.

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.

Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Prevention
  • 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
  • Drug: erlotinib hydrochloride
    Given PO
    Other Names:
    • CP-358,774
    • erlotinib
    • OSI-774
  • Other: placebo
    Given PO
    Other Name: PLCB
  • Other: laboratory biomarker analysis
    Correlative studies
  • Experimental: Arm I (high-dose)
    Patients receive 100 mg of erlotinib hydrochloride PO and two 25 mg of placebo PO QD.
    Interventions:
    • Drug: erlotinib hydrochloride
    • Other: placebo
    • Other: laboratory biomarker analysis
  • Experimental: Arm II (medium dose)
    Patients receive 50 mg of erlotinib hydrochloride PO and one 100 mg of placebo PO QD.
    Interventions:
    • Drug: erlotinib hydrochloride
    • Other: placebo
    • Other: laboratory biomarker analysis
  • Experimental: Arm III (low dose)
    Patients receive 25mg of erlotinib hydrochloride PO and one 100 mg of placebo and one 25 mg of placebo PO QD.
    Interventions:
    • Drug: erlotinib hydrochloride
    • Other: placebo
    • Other: laboratory biomarker analysis
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
48
September 2013
October 2012   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Participants with one or more of the following criteria will be eligible to participate:

    • 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 sigmoidoscopy
  • 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, voriconazole
  • 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
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00754494
NCI-2012-02984, UCI06-8-01, N01CN35160, CDR0000614277
Not Provided
National Cancer Institute (NCI)
National Cancer Institute (NCI)
Not Provided
Principal Investigator: Timothy Morgan Chao Family Comprehensive Cancer Center
National Cancer Institute (NCI)
February 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP