Recurrent Rectal Cancer Clinical Trial
Official title:
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
Status | Completed |
Enrollment | 45 |
Est. completion date | September 2013 |
Est. primary completion date | October 2012 |
Accepts healthy volunteers | No |
Gender | Both |
Age group | 18 Years and older |
Eligibility |
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 |
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Prevention
Country | Name | City | State |
---|---|---|---|
United States | University of Illinois at Chicago | Chicago | Illinois |
United States | VA Long Beach Healthcare System | Long Beach | California |
United States | Chao Family Comprehensive Cancer Center | Orange | California |
Lead Sponsor | Collaborator |
---|---|
National Cancer Institute (NCI) |
United States,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | 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) | No |
Secondary | Change in EGF-inducible Markers - pEGFR in Normal Mucosa | pEGFR expression levels were quantified by immunoblotting and calculated as the ratio of the pEGFR signals to reference signals. A log-transformation of pEGFR was utilized in primary analyses. The general linear model was used to estimate and compare the relative change in median pEGFR with adjustment for actin as a normalizing factor. The estimated relative change (post:pre) in the median, corresponding 95% confidence interval, and p-value for testing the null hypothesis of equal medians comparing pre- and post-measurements were reported. | From baseline to post-treatment (up to 30 days) | No |
Secondary | Change in EGF-inducible Markers - Total EGFR in Normal Mucosa | Total EGFR expression levels were quantified by immunoblotting and calculated as the ratio of the total EGFR signals to reference signals. A log-transformation of total EGFR was utilized in primary analyses. The general linear model was used to estimate and compare the relative change in median total EGFR with adjustment for actin as a normalizing factor. The estimated relative change (post:pre) in the median, corresponding 95% confidence interval, and p-value for testing the null hypothesis of equal medians comparing pre- and post-measurements were reported. | From baseline to post-treatment (up to 30 days) | No |
Secondary | Change in EGF-inducible Markers - pEGFR in ACF | pEGFR expression levels were quantified by immunoblotting and calculated as the ratio of the pEGFR signals to reference signals. A log-transformation of pEGFR was utilized in primary analyses. The general linear model was used to estimate and compare the relative change in median total EGFR with adjustment for actin as a normalizing factor. The estimated relative change (post:pre) in the median, corresponding 95% confidence interval, and p-value for testing the null hypothesis of equal medians comparing pre- and post-measurements were reported. | From baseline to post-treatment (up to 30 days) | No |
Secondary | Change in EGF-inducible Markers - Total EGFR in ACF | Total EGFR expression levels were quantified by immunoblotting and calculated as the ratio of the total EGFR signals to reference signals. A log-transformation of total EGFR was utilized in primary analyses. The general linear model was used to estimate and compare the relative change in median total EGFR with adjustment for actin as a normalizing factor. The estimated relative change (post:pre) in the median, corresponding 95% confidence interval, and p-value for testing the null hypothesis of equal medians comparing pre- and post-measurements were reported. | From baseline to post-treatment (up to 30 days) | No |
Secondary | ACF: Normal Mucosa pERK Ratio | 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. | Up to day 30 | No |
Secondary | Plasma Erlotinib Concentration (ng/mL) | Will be quantified in biopsy samples using appropriate descriptive statistics (means and standard deviations). | Up to day 30 | No |
Secondary | Plasma OSI-420 Concentration (ng/mL) | Will be quantified in biopsy samples using appropriate descriptive statistics (means and standard deviations). | Up to day 30 | No |
Secondary | Normal Mucosa Erlotinib Concentration (ng/mg) | Will be quantified in biopsy samples using appropriate descriptive statistics (means and standard deviations). | Up to day 30 | No |
Secondary | Normal Mucosa OSI-420 Concentration (ng/mg) | Will be quantified in biopsy samples using appropriate descriptive statistics (means and standard deviations). | Up to day 30 | No |
Secondary | Number of Participants Reported at Least 1 Side Effect During the Study | Described for each arm using frequencies. The onset of adverse events is between randomization date and off-study date. | Up to 9 weeks | Yes |
Secondary | Number of Participants Reported at Least 1 Rash Side Effect During the Study | Described for each arm using frequencies. | Up to 9 weeks | Yes |
Secondary | Number of Participants Reported at Least 1 Diarrhea Side Effect During the Study | Described for each arm using frequencies. | Up to 9 weeks | Yes |
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