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

• Sponsor: National Cancer Institute (NCI) (NIH)
• Overall Status: Completed
• CT.gov ID: NCT00754494
• Collaborator: (none)
• Enrollment: 45
• Locations: 3
• Arms: 3
• Duration (Months): 62
• Patients Per Site: 15
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
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; Other: placebo; Other: laboratory biomarker analysis	Phase 2

Detailed Description

PRIMARY OBJECTIVES:

1. 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:

1. 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.

2. To determine the mean decrease from baseline of the ACF: normal mucosa pERK ratio pre and post 8-30 days of erlotinib.

3. To determine erlotinib concentration in plasma and colorectal tissue at 25 mg, 50 mg and 100 mg doses after 8-30 days of therapy.

4. 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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 45 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Prevention
• Official Title: A Phase IIa Randomized, Double-Blind Trial of Erlotinib in Inhibiting EGF Receptor Signaling in Aberrant Crypt Foci of the Colon
• Study Start Date: Jul 1, 2008
• Actual Primary Completion Date: Oct 1, 2012
• Actual Study Completion Date: Sep 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Erlotinib Hydrochloride (25 mg) Patients receive 25mg of erlotinib hydrochloride PO and one 100 mg of placebo and one 25 mg of placebo PO QD.	Drug: erlotinib hydrochloride; Given PO; Other Names: CP-358,774 erlotinib OSI-774 ; Other: placebo; Given PO; Other Names: PLCB ; Other: laboratory biomarker analysis; Correlative studies
Experimental: Erlotinib Hydrochloride (50 mg) Patients receive 50 mg of erlotinib hydrochloride PO and one 100 mg of placebo PO QD.	Drug: erlotinib hydrochloride; Given PO; Other Names: CP-358,774 erlotinib OSI-774 ; Other: placebo; Given PO; Other Names: PLCB ; Other: laboratory biomarker analysis; Correlative studies
Experimental: Erlotinib Hydrochloride (100 mg) Patients receive 100 mg of erlotinib hydrochloride PO and two 25 mg of placebo PO QD.	Drug: erlotinib hydrochloride; Given PO; Other Names: CP-358,774 erlotinib OSI-774 ; Other: placebo; Given PO; Other Names: PLCB ; Other: laboratory biomarker analysis; Correlative studies

Outcome Measures

Primary Outcome Measures

1. Change in ACF pERK Levels [From baseline to post-treatment (up to 30 days)]

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

Secondary Outcome Measures

1. Change in EGF-inducible Markers - pEGFR in Normal Mucosa [From baseline to post-treatment (up to 30 days)]

   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.

2. Change in EGF-inducible Markers - Total EGFR in Normal Mucosa [From baseline to post-treatment (up to 30 days)]

   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.

3. Change in EGF-inducible Markers - pEGFR in ACF [From baseline to post-treatment (up to 30 days)]

   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.

4. Change in EGF-inducible Markers - Total EGFR in ACF [From baseline to post-treatment (up to 30 days)]

   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.

5. ACF: Normal Mucosa pERK Ratio [Up to day 30]

   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.

6. Plasma Erlotinib Concentration (ng/mL) [Up to day 30]

   Will be quantified in biopsy samples using appropriate descriptive statistics (means and standard deviations).

7. Plasma OSI-420 Concentration (ng/mL) [Up to day 30]

   Will be quantified in biopsy samples using appropriate descriptive statistics (means and standard deviations).

8. Normal Mucosa Erlotinib Concentration (ng/mg) [Up to day 30]

   Will be quantified in biopsy samples using appropriate descriptive statistics (means and standard deviations).

9. Normal Mucosa OSI-420 Concentration (ng/mg) [Up to day 30]

   Will be quantified in biopsy samples using appropriate descriptive statistics (means and standard deviations).

10. Number of Participants Reported at Least 1 Side Effect During the Study [Up to 9 weeks]

    Described for each arm using frequencies. The onset of adverse events is between randomization date and off-study date.

11. Number of Participants Reported at Least 1 Rash Side Effect During the Study [Up to 9 weeks]

    Described for each arm using frequencies.

12. Number of Participants Reported at Least 1 Diarrhea Side Effect During the Study [Up to 9 weeks]

    Described for each arm using frequencies.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	VA Long Beach Healthcare System	Long Beach	California	United States	90822
2	Chao Family Comprehensive Cancer Center	Orange	California	United States	92868
3	University of Illinois at Chicago	Chicago	Illinois	United States	60612

Sponsors and Collaborators

• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Timothy Morgan, Chao Family Comprehensive Cancer Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: National Cancer Institute (NCI)
• ClinicalTrials.gov Identifier: NCT00754494
• Other Study ID Numbers: NCI-2012-02984; UCI06-8-01; N01CN35160; CDR0000614277
• First Posted: Sep 18, 2008
• Last Update Posted: Jan 6, 2015
• Last Verified: Mar 1, 2014

• Additional relevant MeSH terms: Rectal Neoplasms; Colonic Neoplasms; Adenomatous Polyps; Recurrence; Erlotinib Hydrochloride

Study Results

Participant Flow

Arm/Group Title	Arm I (25 mg)	Arm II (50 mg)	Arm III (100 mg)
Arm/Group Description	Patients receive 25mg of erlotinib hydrochloride PO and one 100 mg of placebo and one 25 mg of placebo PO QD. erlotinib hydrochloride: Given PO placebo: Given PO laboratory biomarker analysis: Correlative studies	Patients receive 50 mg of erlotinib hydrochloride PO and one 100 mg of placebo PO QD. erlotinib hydrochloride: Given PO placebo: Given PO laboratory biomarker analysis: Correlative studies	Patients receive 100 mg of erlotinib hydrochloride PO and two 25 mg of placebo PO QD. erlotinib hydrochloride: Given PO placebo: Given PO laboratory biomarker analysis: Correlative studies
Period Title: Overall Study
STARTED	15	15	15
COMPLETED	13	15	14
NOT COMPLETED	2	0	1

Baseline Characteristics

Arm/Group Title	Arm I (25 mg)	Arm II (50 mg)	Arm III (100 mg)	Total
Arm/Group Description	Patients receive 25mg of erlotinib hydrochloride PO and one 100 mg of placebo and one 25 mg of placebo PO QD. erlotinib hydrochloride: Given PO placebo: Given PO laboratory biomarker analysis: Correlative studies	Patients receive 50 mg of erlotinib hydrochloride PO and one 100 mg of placebo PO QD. erlotinib hydrochloride: Given PO placebo: Given PO laboratory biomarker analysis: Correlative studies	Patients receive 100 mg of erlotinib hydrochloride PO and two 25 mg of placebo PO QD. erlotinib hydrochloride: Given PO placebo: Given PO laboratory biomarker analysis: Correlative studies	Total of all reporting groups
Overall Participants	15	15	15	45
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	63.67 (4.43)	62.47 (6.03)	60.67 (7.42)	62.27 (6.08)
Sex: Female, Male (Count of Participants)
Female	2 13.3%	1 6.7%	5 33.3%	8 17.8%
Male	13 86.7%	14 93.3%	10 66.7%	37 82.2%

Outcome Measures

1. Primary Outcome

Title	Change in ACF pERK Levels
Description	Quantification will be performed by Western blot analysis. Tested using paired t-test with a two-sided significance level of 0.05.
Time Frame	From baseline to post-treatment (up to 30 days)

Outcome Measure Data

Analysis Population Description

Change in ACF pERK levels not reported as the assay did not demonstrate signaling

Arm/Group Title	Arm I (25 mg)	Arm II (50 mg)	Arm III (100 mg)
Arm/Group Description	Patients receive 25mg of erlotinib hydrochloride PO and one 100 mg of placebo and one 25 mg of placebo PO QD. erlotinib hydrochloride: Given PO placebo: Given PO laboratory biomarker analysis: Correlative studies The range of days on treatment is 10 to 29 days	Patients receive 50 mg of erlotinib hydrochloride PO and one 100 mg of placebo PO QD. erlotinib hydrochloride: Given PO placebo: Given PO laboratory biomarker analysis: Correlative studies The range of days on treatment is 8 to 28 days	Patients receive 100 mg of erlotinib hydrochloride PO and two 25 mg of placebo PO QD. erlotinib hydrochloride: Given PO placebo: Given PO laboratory biomarker analysis: Correlative studies The range of days on treatment is 7 to 23 days
Measure Participants	0	0	0

2. Secondary Outcome

Title	Change in EGF-inducible Markers - pEGFR in Normal Mucosa
Description	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.
Time Frame	From baseline to post-treatment (up to 30 days)

Outcome Measure Data

Analysis Population Description

Outcome measure data is reported based on the evaluable samples collected and available results.

Arm/Group Title	Arm I (25 mg)	Arm II (50 mg)	Arm III (100 mg)
Arm/Group Description	Patients receive 25mg of erlotinib hydrochloride PO and one 100 mg of placebo and one 25 mg of placebo PO QD. erlotinib hydrochloride: Given PO placebo: Given PO laboratory biomarker analysis: Correlative studies The range of days on treatment is 10 to 29 days	Patients receive 50 mg of erlotinib hydrochloride PO and one 100 mg of placebo PO QD. erlotinib hydrochloride: Given PO placebo: Given PO laboratory biomarker analysis: Correlative studies The range of days on treatment is 8 to 28 days	Patients receive 100 mg of erlotinib hydrochloride PO and two 25 mg of placebo PO QD. erlotinib hydrochloride: Given PO placebo: Given PO laboratory biomarker analysis: Correlative studies The range of days on treatment is 7 to 23 days
Measure Participants	14	14	13
Geometric Mean (95% Confidence Interval) [expression level]	0.84	1.65	0.97

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm I (25 mg)
	Comments	A log-transformation of pEGFR was utilized in primary analyses because of the highly skewed distribution observed in this outcome. 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.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.762
	Comments
	Method	General Linear Model
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Arm II (50 mg)
	Comments	A log-transformation of pEGFR was utilized in primary analyses because of the highly skewed distribution observed in this outcome. 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.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.125
	Comments
	Method	General Linear Model
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Arm III (100 mg)
	Comments	A log-transformation of pEGFR was utilized in primary analyses because of the highly skewed distribution observed in this outcome. 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.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.855
	Comments
	Method	General Linear Model
	Comments

3. Secondary Outcome

Title	Change in EGF-inducible Markers - Total EGFR in Normal Mucosa
Description	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.
Time Frame	From baseline to post-treatment (up to 30 days)

Outcome Measure Data

Analysis Population Description

Outcome measure data is reported based on the evaluable samples collected and available results.

Arm/Group Title	Arm I (25 mg)	Arm II (50 mg)	Arm III (100 mg)
Arm/Group Description	Patients receive 25mg of erlotinib hydrochloride PO and one 100 mg of placebo and one 25 mg of placebo PO QD. erlotinib hydrochloride: Given PO placebo: Given PO laboratory biomarker analysis: Correlative studies The range of days on treatment is 10 to 29 days	Patients receive 50 mg of erlotinib hydrochloride PO and one 100 mg of placebo PO QD. erlotinib hydrochloride: Given PO placebo: Given PO laboratory biomarker analysis: Correlative studies The range of days on treatment is 8 to 28 days	Patients receive 100 mg of erlotinib hydrochloride PO and two 25 mg of placebo PO QD. erlotinib hydrochloride: Given PO placebo: Given PO laboratory biomarker analysis: Correlative studies The range of days on treatment is 7 to 23 days
Measure Participants	14	14	13
Geometric Mean (95% Confidence Interval) [expression level]	2.02	1.91	1.23

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm I (25 mg)
	Comments	A log-transformation of total EGFR was utilized in primary analyses because of the highly skewed distribution observed in this outcome. 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.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.369
	Comments
	Method	General Linear Model
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Arm II (50 mg)
	Comments	A log-transformation of total EGFR was utilized in primary analyses because of the highly skewed distribution observed in this outcome. 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.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.085
	Comments
	Method	General Linear Model
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Arm III (100 mg)
	Comments	A log-transformation of total EGFR was utilized in primary analyses because of the highly skewed distribution observed in this outcome. 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.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.233
	Comments
	Method	General Linear Model
	Comments

4. Secondary Outcome

Title	Change in EGF-inducible Markers - pEGFR in ACF
Description	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.
Time Frame	From baseline to post-treatment (up to 30 days)

Outcome Measure Data

Analysis Population Description

Outcome measure data is reported based on the evaluable samples collected and available results.

Arm/Group Title	Arm I (25 mg)	Arm II (50 mg)	Arm III (100 mg)
Arm/Group Description	Patients receive 25mg of erlotinib hydrochloride PO and one 100 mg of placebo and one 25 mg of placebo PO QD. erlotinib hydrochloride: Given PO placebo: Given PO laboratory biomarker analysis: Correlative studies The range of days on treatment is 10 to 29 days	Patients receive 50 mg of erlotinib hydrochloride PO and one 100 mg of placebo PO QD. erlotinib hydrochloride: Given PO placebo: Given PO laboratory biomarker analysis: Correlative studies The range of days on treatment is 8 to 28 days	Patients receive 100 mg of erlotinib hydrochloride PO and two 25 mg of placebo PO QD. erlotinib hydrochloride: Given PO placebo: Given PO laboratory biomarker analysis: Correlative studies The range of days on treatment is 7 to 23 days
Measure Participants	14	14	14
Geometric Mean (95% Confidence Interval) [expression level]	1.19	1.93	1.40

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm I (25 mg)
	Comments	A log-transformation of pEGFR was utilized in primary analyses because of the highly skewed distribution observed in this outcome. 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.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.651
	Comments
	Method	General Linear Model
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Arm II (50 mg)
	Comments	A log-transformation of pEGFR was utilized in primary analyses because of the highly skewed distribution observed in this outcome. 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.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.030
	Comments
	Method	General Linear Model
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Arm III (100 mg)
	Comments	A log-transformation of pEGFR was utilized in primary analyses because of the highly skewed distribution observed in this outcome. 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.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.261
	Comments
	Method	General Linear Model
	Comments

5. Secondary Outcome

Title	Change in EGF-inducible Markers - Total EGFR in ACF
Description	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.
Time Frame	From baseline to post-treatment (up to 30 days)

Outcome Measure Data

Analysis Population Description

Outcome measure data is reported based on the evaluable samples collected and available results.

Arm/Group Title	Arm I (25 mg)	Arm II (50 mg)	Arm III (100 mg)
Arm/Group Description	Patients receive 25mg of erlotinib hydrochloride PO and one 100 mg of placebo and one 25 mg of placebo PO QD. erlotinib hydrochloride: Given PO placebo: Given PO laboratory biomarker analysis: Correlative studies The range of days on treatment is 10 to 29 days	Patients receive 50 mg of erlotinib hydrochloride PO and one 100 mg of placebo PO QD. erlotinib hydrochloride: Given PO placebo: Given PO laboratory biomarker analysis: Correlative studies The range of days on treatment is 8 to 28 days	Patients receive 100 mg of erlotinib hydrochloride PO and two 25 mg of placebo PO QD. erlotinib hydrochloride: Given PO placebo: Given PO laboratory biomarker analysis: Correlative studies The range of days on treatment is 7 to 23 days
Measure Participants	14	14	14
Geometric Mean (95% Confidence Interval) [expression level]	1.33	2.22	1.94

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm I (25 mg)
	Comments	A log-transformation of total EGFR was utilized in primary analyses because of the highly skewed distribution observed in this outcome. 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.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.654
	Comments
	Method	General Linear Model
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Arm II (50 mg)
	Comments	A log-transformation of total EGFR was utilized in primary analyses because of the highly skewed distribution observed in this outcome. 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.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.030
	Comments
	Method	General Linear Model
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Arm III (100 mg)
	Comments	A log-transformation of total EGFR was utilized in primary analyses because of the highly skewed distribution observed in this outcome. 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.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.083
	Comments
	Method	General Linear Model
	Comments

6. Secondary Outcome

Title	ACF: Normal Mucosa pERK Ratio
Description	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.
Time Frame	Up to day 30

Outcome Measure Data

Analysis Population Description

ACF: pERK ratio not reported as the assay did not demonstrate signaling in ACF pERK levels

Arm/Group Title	Arm I (25 mg)	Arm II (50 mg)	Arm III (100 mg)
Arm/Group Description	Patients receive 25mg of erlotinib hydrochloride PO and one 100 mg of placebo and one 25 mg of placebo PO QD. erlotinib hydrochloride: Given PO placebo: Given PO laboratory biomarker analysis: Correlative studies The range of days on treatment is 10 to 29 days	Patients receive 50 mg of erlotinib hydrochloride PO and one 100 mg of placebo PO QD. erlotinib hydrochloride: Given PO placebo: Given PO laboratory biomarker analysis: Correlative studies The range of days on treatment is 8 to 28 days	Patients receive 100 mg of erlotinib hydrochloride PO and two 25 mg of placebo PO QD. erlotinib hydrochloride: Given PO placebo: Given PO laboratory biomarker analysis: Correlative studies The range of days on treatment is 7 to 23 days
Measure Participants	0	0	0

7. Secondary Outcome

Title	Plasma Erlotinib Concentration (ng/mL)
Description	Will be quantified in biopsy samples using appropriate descriptive statistics (means and standard deviations).
Time Frame	Up to day 30

Outcome Measure Data

Analysis Population Description

Outcome measure data is reported based on the evaluable samples collected and available results.

Arm/Group Title	Arm I (25 mg)	Arm II (50 mg)	Arm III (100 mg)
Arm/Group Description	Patients receive 25mg of erlotinib hydrochloride PO and one 100 mg of placebo and one 25 mg of placebo PO QD. erlotinib hydrochloride: Given PO placebo: Given PO laboratory biomarker analysis: Correlative studies The range of days on treatment is 10 to 29 days	Patients receive 50 mg of erlotinib hydrochloride PO and one 100 mg of placebo PO QD. erlotinib hydrochloride: Given PO placebo: Given PO laboratory biomarker analysis: Correlative studies The range of days on treatment is 8 to 28 days	Patients receive 100 mg of erlotinib hydrochloride PO and two 25 mg of placebo PO QD. erlotinib hydrochloride: Given PO placebo: Given PO laboratory biomarker analysis: Correlative studies The range of days on treatment is 7 to 23 days
Measure Participants	14	14	13
Mean (Standard Deviation) [ng/mL]	232.29 (160.6)	486.56 (211.8)	1280.84 (788.3)

8. Secondary Outcome

Title	Plasma OSI-420 Concentration (ng/mL)
Description	Will be quantified in biopsy samples using appropriate descriptive statistics (means and standard deviations).
Time Frame	Up to day 30

Outcome Measure Data

Analysis Population Description

Outcome measure data is reported based on the evaluable samples collected and available results.

Arm/Group Title	Arm I (25 mg)	Arm II (50 mg)	Arm III (100 mg)
Arm/Group Description	Patients receive 25mg of erlotinib hydrochloride PO and one 100 mg of placebo and one 25 mg of placebo PO QD. erlotinib hydrochloride: Given PO placebo: Given PO laboratory biomarker analysis: Correlative studies The range of days on treatment is 10 to 29 days	Patients receive 50 mg of erlotinib hydrochloride PO and one 100 mg of placebo PO QD. erlotinib hydrochloride: Given PO placebo: Given PO laboratory biomarker analysis: Correlative studies The range of days on treatment is 8 to 28 days	Patients receive 100 mg of erlotinib hydrochloride PO and two 25 mg of placebo PO QD. erlotinib hydrochloride: Given PO placebo: Given PO laboratory biomarker analysis: Correlative studies The range of days on treatment is 7 to 23 days
Measure Participants	13	14	13
Mean (Standard Deviation) [ng/mL]	17.77 (12.3)	33.87 (14.1)	117.98 (84.5)

9. Secondary Outcome

Title	Normal Mucosa Erlotinib Concentration (ng/mg)
Description	Will be quantified in biopsy samples using appropriate descriptive statistics (means and standard deviations).
Time Frame	Up to day 30

Outcome Measure Data

Analysis Population Description

Outcome measure data is reported based on the evaluable samples collected and available results.

Arm/Group Title	Arm I (25 mg)	Arm II (50 mg)	Arm III (100 mg)
Arm/Group Description	Patients receive 25mg of erlotinib hydrochloride PO and one 100 mg of placebo and one 25 mg of placebo PO QD. erlotinib hydrochloride: Given PO placebo: Given PO laboratory biomarker analysis: Correlative studies The range of days on treatment is 10 to 29 days	Patients receive 50 mg of erlotinib hydrochloride PO and one 100 mg of placebo PO QD. erlotinib hydrochloride: Given PO placebo: Given PO laboratory biomarker analysis: Correlative studies The range of days on treatment is 8 to 28 days	Patients receive 100 mg of erlotinib hydrochloride PO and two 25 mg of placebo PO QD. erlotinib hydrochloride: Given PO placebo: Given PO laboratory biomarker analysis: Correlative studies The range of days on treatment is 7 to 23 days
Measure Participants	12	12	12
Mean (Standard Deviation) [ng/mg]	0.36 (0.18)	1.38 (1.23)	3.25 (4.62)

10. Secondary Outcome

Title	Normal Mucosa OSI-420 Concentration (ng/mg)
Description	Will be quantified in biopsy samples using appropriate descriptive statistics (means and standard deviations).
Time Frame	Up to day 30

Outcome Measure Data

Analysis Population Description

Outcome measure data is reported based on the evaluable samples collected and available results.

Arm/Group Title	Arm I (25 mg)	Arm II (50 mg)	Arm III (100 mg)
Arm/Group Description	Patients receive 25mg of erlotinib hydrochloride PO and one 100 mg of placebo and one 25 mg of placebo PO QD. erlotinib hydrochloride: Given PO placebo: Given PO laboratory biomarker analysis: Correlative studies The range of days on treatment is 10 to 29 days	Patients receive 50 mg of erlotinib hydrochloride PO and one 100 mg of placebo PO QD. erlotinib hydrochloride: Given PO placebo: Given PO laboratory biomarker analysis: Correlative studies The range of days on treatment is 8 to 28 days	Patients receive 100 mg of erlotinib hydrochloride PO and two 25 mg of placebo PO QD. erlotinib hydrochloride: Given PO placebo: Given PO laboratory biomarker analysis: Correlative studies The range of days on treatment is 7 to 23 days
Measure Participants	4	10	11
Mean (Standard Deviation) [ng/mg]	0.04 (0.01)	0.17 (0.15)	0.29 (0.24)

11. Secondary Outcome

Title	Number of Participants Reported at Least 1 Side Effect During the Study
Description	Described for each arm using frequencies. The onset of adverse events is between randomization date and off-study date.
Time Frame	Up to 9 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm I (25 mg)	Arm II (50 mg)	Arm III (100 mg)
Arm/Group Description	Patients receive 25mg of erlotinib hydrochloride PO and one 100 mg of placebo and one 25 mg of placebo PO QD. erlotinib hydrochloride: Given PO placebo: Given PO laboratory biomarker analysis: Correlative studies The range of days on treatment is 10 to 29 days	Patients receive 50 mg of erlotinib hydrochloride PO and one 100 mg of placebo PO QD. erlotinib hydrochloride: Given PO placebo: Given PO laboratory biomarker analysis: Correlative studies The range of days on treatment is 8 to 28 days	Patients receive 100 mg of erlotinib hydrochloride PO and two 25 mg of placebo PO QD. erlotinib hydrochloride: Given PO placebo: Given PO laboratory biomarker analysis: Correlative studies The range of days on treatment is 7 to 23 days
Measure Participants	15	15	15
At least 1 adverse event reported	12 80%	13 86.7%	13 86.7%
No adverse event reported	3 20%	2 13.3%	2 13.3%

12. Secondary Outcome

Title	Number of Participants Reported at Least 1 Rash Side Effect During the Study
Description	Described for each arm using frequencies.
Time Frame	Up to 9 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm I (25 mg)	Arm II (50 mg)	Arm III (100 mg)
Arm/Group Description	Patients receive 25mg of erlotinib hydrochloride PO and one 100 mg of placebo and one 25 mg of placebo PO QD. erlotinib hydrochloride: Given PO placebo: Given PO laboratory biomarker analysis: Correlative studies The range of days on treatment is 10 to 29 days	Patients receive 50 mg of erlotinib hydrochloride PO and one 100 mg of placebo PO QD. erlotinib hydrochloride: Given PO placebo: Given PO laboratory biomarker analysis: Correlative studies The range of days on treatment is 8 to 28 days	Patients receive 100 mg of erlotinib hydrochloride PO and two 25 mg of placebo PO QD. erlotinib hydrochloride: Given PO placebo: Given PO laboratory biomarker analysis: Correlative studies The range of days on treatment is 7 to 23 days
Measure Participants	15	15	15
At least 1 rash AE reported	5 33.3%	6 40%	12 80%
No rash AE reported	10 66.7%	9 60%	3 20%

13. Secondary Outcome

Title	Number of Participants Reported at Least 1 Diarrhea Side Effect During the Study
Description	Described for each arm using frequencies.
Time Frame	Up to 9 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm I (25 mg)	Arm II (50 mg)	Arm III (100 mg)
Arm/Group Description	Patients receive 25mg of erlotinib hydrochloride PO and one 100 mg of placebo and one 25 mg of placebo PO QD. erlotinib hydrochloride: Given PO placebo: Given PO laboratory biomarker analysis: Correlative studies The range of days on treatment is 10 to 29 days	Patients receive 50 mg of erlotinib hydrochloride PO and one 100 mg of placebo PO QD. erlotinib hydrochloride: Given PO placebo: Given PO laboratory biomarker analysis: Correlative studies The range of days on treatment is 8 to 28 days	Patients receive 100 mg of erlotinib hydrochloride PO and two 25 mg of placebo PO QD. erlotinib hydrochloride: Given PO placebo: Given PO laboratory biomarker analysis: Correlative studies The range of days on treatment is 7 to 23 days
Measure Participants	15	15	15
At least 1 diarrhea AE reported	4 26.7%	4 26.7%	5 33.3%
No diarrhea AE reported	11 73.3%	11 73.3%	10 66.7%

Adverse Events

Time Frame	The onset date of adverse event is between the randomization date and the date of off-study, up to 95 days.
Arm/Group Title	Arm I (25 mg)		Arm II (50 mg)		Arm III (100 mg)
Arm/Group Description	Patients receive 25mg of erlotinib hydrochloride PO and one 100 mg of placebo and one 25 mg of placebo PO QD. erlotinib hydrochloride: Given PO placebo: Given PO laboratory biomarker analysis: Correlative studies		Patients receive 50 mg of erlotinib hydrochloride PO and one 100 mg of placebo PO QD. erlotinib hydrochloride: Given PO placebo: Given PO laboratory biomarker analysis: Correlative studies		Patients receive 100 mg of erlotinib hydrochloride PO and two 25 mg of placebo PO QD. erlotinib hydrochloride: Given PO placebo: Given PO laboratory biomarker analysis: Correlative studies
All Cause Mortality
	Arm I (25 mg)		Arm II (50 mg)		Arm III (100 mg)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Arm I (25 mg)		Arm II (50 mg)		Arm III (100 mg)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/15 (6.7%)		0/15 (0%)		0/15 (0%)
Cardiac disorders
CHEST PAIN	1/15 (6.7%)	1	0/15 (0%)	0	0/15 (0%)	0
Other (Not Including Serious) Adverse Events
	Arm I (25 mg)		Arm II (50 mg)		Arm III (100 mg)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	12/15 (80%)		13/15 (86.7%)		13/15 (86.7%)
Ear and labyrinth disorders
EARACHE	0/15 (0%)	0	0/15 (0%)	0	1/15 (6.7%)	1
Eye disorders
BLURRING OF VISION	0/15 (0%)	0	1/15 (6.7%)	1	0/15 (0%)	0
DRY EYE	1/15 (6.7%)	1	0/15 (0%)	0	0/15 (0%)	0
DRY EYES	0/15 (0%)	0	2/15 (13.3%)	2	1/15 (6.7%)	1
DRY ITCHY EYE	2/15 (13.3%)	2	0/15 (0%)	0	0/15 (0%)	0
DRYNESS OF EYES	1/15 (6.7%)	1	0/15 (0%)	0	0/15 (0%)	0
ITCHINESS OF EYES	1/15 (6.7%)	1	0/15 (0%)	0	0/15 (0%)	0
RED PUFFY EYES	0/15 (0%)	0	0/15 (0%)	0	1/15 (6.7%)	1
SEEING BLACK SPOTS AND FLASHING LIGHTS IN LEFT EYE	0/15 (0%)	0	0/15 (0%)	0	1/15 (6.7%)	1
Gastrointestinal disorders
CONSTIPATION	0/15 (0%)	0	1/15 (6.7%)	2	0/15 (0%)	0
DIARRHEA	3/15 (20%)	3	3/15 (20%)	4	4/15 (26.7%)	5
DIARRHEA-FREQUENT BM'S	0/15 (0%)	0	0/15 (0%)	0	1/15 (6.7%)	1
DRY MOUTH	0/15 (0%)	0	0/15 (0%)	0	1/15 (6.7%)	1
FLATULENCE	0/15 (0%)	0	1/15 (6.7%)	2	0/15 (0%)	0
HEARTBURN	1/15 (6.7%)	1	0/15 (0%)	0	0/15 (0%)	0
INCARCERATED HERNIA	1/15 (6.7%)	1	0/15 (0%)	0	0/15 (0%)	0
LOOSE STOOLS	0/15 (0%)	0	1/15 (6.7%)	1	0/15 (0%)	0
LOSS OF APPETITE	1/15 (6.7%)	1	0/15 (0%)	0	1/15 (6.7%)	1
LOTS OF GAS	1/15 (6.7%)	1	0/15 (0%)	0	0/15 (0%)	0
MILD DIARRHEA	1/15 (6.7%)	1	0/15 (0%)	0	0/15 (0%)	0
MILD INDIGESTION	0/15 (0%)	0	1/15 (6.7%)	1	0/15 (0%)	0
NAUSEA	2/15 (13.3%)	2	2/15 (13.3%)	2	0/15 (0%)	0
PAIN ON ABDOMEN	0/15 (0%)	0	0/15 (0%)	0	1/15 (6.7%)	1
VOMIT	0/15 (0%)	0	1/15 (6.7%)	1	0/15 (0%)	0
General disorders
COLD	1/15 (6.7%)	1	0/15 (0%)	0	0/15 (0%)	0
FATIGUE	1/15 (6.7%)	1	0/15 (0%)	0	3/15 (20%)	3
FLU	0/15 (0%)	0	1/15 (6.7%)	1	0/15 (0%)	0
Musculoskeletal and connective tissue disorders
DEEP BRUISED LFT LEG PAIN	0/15 (0%)	0	1/15 (6.7%)	1	0/15 (0%)	0
DULL SORENESS IN LEG	0/15 (0%)	0	1/15 (6.7%)	1	0/15 (0%)	0
PAIN ON FOOT	0/15 (0%)	0	0/15 (0%)	0	1/15 (6.7%)	1
SHOULDER PAIN	1/15 (6.7%)	1	0/15 (0%)	0	0/15 (0%)	0
SWOLLEN LEFT KNEE	1/15 (6.7%)	1	0/15 (0%)	0	0/15 (0%)	0
Nervous system disorders
DIZZINESS	0/15 (0%)	0	0/15 (0%)	0	2/15 (13.3%)	2
HEADACHE	1/15 (6.7%)	1	0/15 (0%)	0	0/15 (0%)	0
LIGHT HEADED	0/15 (0%)	0	1/15 (6.7%)	1	0/15 (0%)	0
Psychiatric disorders
DEPRESSION	0/15 (0%)	0	0/15 (0%)	0	1/15 (6.7%)	1
IRRITABLE-MOOD ALTERATION	0/15 (0%)	0	0/15 (0%)	0	1/15 (6.7%)	1
Renal and urinary disorders
BLUE COLORED URINE	0/15 (0%)	0	0/15 (0%)	0	1/15 (6.7%)	1
BLUE/GREEN COLORED URINE	0/15 (0%)	0	0/15 (0%)	0	1/15 (6.7%)	1
Respiratory, thoracic and mediastinal disorders
BLOODY NOSE	0/15 (0%)	0	0/15 (0%)	0	1/15 (6.7%)	1
COUGH	2/15 (13.3%)	2	0/15 (0%)	0	1/15 (6.7%)	1
NOSE BLEED	0/15 (0%)	0	1/15 (6.7%)	1	0/15 (0%)	0
RUNNY NOSE	0/15 (0%)	0	1/15 (6.7%)	1	0/15 (0%)	0
SHORT OF BREATH EASILY	1/15 (6.7%)	1	0/15 (0%)	0	0/15 (0%)	0
SHORT OF BREATH-DYSPNEA	0/15 (0%)	0	0/15 (0%)	0	1/15 (6.7%)	1
SORE THROAT	1/15 (6.7%)	1	0/15 (0%)	0	0/15 (0%)	0
Skin and subcutaneous tissue disorders
80% DIMINISHED SEBORRHEIC KERATOSIS SKIN LESIONS	1/15 (6.7%)	1	0/15 (0%)	0	0/15 (0%)	0
ALLERGIC REACTION: RASH ON THE FACE	0/15 (0%)	0	0/15 (0%)	0	1/15 (6.7%)	1
CANKER SORES	0/15 (0%)	0	0/15 (0%)	0	1/15 (6.7%)	1
CLEARED UP ACNE ON MY FOREHEAD	1/15 (6.7%)	1	0/15 (0%)	0	0/15 (0%)	0
DRY & ITCHY SKIN	1/15 (6.7%)	1	0/15 (0%)	0	0/15 (0%)	0
DRY SKIN	3/15 (20%)	3	2/15 (13.3%)	2	5/15 (33.3%)	5
DRY SKIN AROUND NOSE	0/15 (0%)	0	1/15 (6.7%)	1	0/15 (0%)	0
DRY SKIN ON NOSE	0/15 (0%)	0	1/15 (6.7%)	1	0/15 (0%)	0
DRY SKIN-(LEGS)	0/15 (0%)	0	0/15 (0%)	0	1/15 (6.7%)	1
DRYNESS OF SKIN ON FACE	0/15 (0%)	0	1/15 (6.7%)	1	0/15 (0%)	0
FACE PIMPLES	0/15 (0%)	0	1/15 (6.7%)	1	0/15 (0%)	0
FACE SORE	0/15 (0%)	0	1/15 (6.7%)	1	0/15 (0%)	0
FOLLICULAR RASH ON TORSO	0/15 (0%)	0	1/15 (6.7%)	1	0/15 (0%)	0
MILD RASH IN THE BUTTOCK	1/15 (6.7%)	1	0/15 (0%)	0	0/15 (0%)	0
MOUTH SORES	0/15 (0%)	0	1/15 (6.7%)	1	0/15 (0%)	0
PAINFUL ITCHY & TENDER SCALP	0/15 (0%)	0	0/15 (0%)	0	1/15 (6.7%)	1
RASH	3/15 (20%)	3	0/15 (0%)	0	4/15 (26.7%)	4
RASH ON CHEST	1/15 (6.7%)	1	0/15 (0%)	0	2/15 (13.3%)	2
RASH ON FACE, CHEST AND SHOULDER	0/15 (0%)	0	0/15 (0%)	0	1/15 (6.7%)	1
RASH ON FACE, CHEST, AND BEHIND EARS	0/15 (0%)	0	1/15 (6.7%)	1	0/15 (0%)	0
RASH ON FACE, SCALP AND CHEST	0/15 (0%)	0	1/15 (6.7%)	1	0/15 (0%)	0
RASH ON FACE, SCALP, CHEST	0/15 (0%)	0	1/15 (6.7%)	1	0/15 (0%)	0
RASH ON FACE, SCALP, CHEST, BACK, EXTREMITIES	0/15 (0%)	0	0/15 (0%)	0	1/15 (6.7%)	1
RASH ON FOOT	0/15 (0%)	0	1/15 (6.7%)	1	0/15 (0%)	0
RASH ON FOREHEAD/NOSE/CHEST	0/15 (0%)	0	0/15 (0%)	0	1/15 (6.7%)	1
RAW NOSE	0/15 (0%)	0	1/15 (6.7%)	1	0/15 (0%)	0
RED ITCHY FACE RASH ON CHEEKS & NOSE	0/15 (0%)	0	0/15 (0%)	0	1/15 (6.7%)	1
RED RASH-FACE PEELING & NOW WHITE HEAD PIMPLES	0/15 (0%)	0	0/15 (0%)	0	1/15 (6.7%)	1
RED RASH-FACE,NOSE, & CHEST	0/15 (0%)	0	0/15 (0%)	0	1/15 (6.7%)	1
RED RASH-FACE-NECK-CHEST & SCALP-ITCHY	0/15 (0%)	0	0/15 (0%)	0	1/15 (6.7%)	1
RED,BUMPY FACE & CHEST RASH	1/15 (6.7%)	1	0/15 (0%)	0	0/15 (0%)	0
SWOLLEN FACE	0/15 (0%)	0	0/15 (0%)	0	1/15 (6.7%)	1
ULCER ON MUCOUS MEMBRANE IN MOUTH	0/15 (0%)	0	1/15 (6.7%)	1	0/15 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.