Bladder Carcinoma, Recurrent Bladder Carcinoma
Conditions
Brief summary
This randomized phase II trial studies how well erlotinib hydrochloride works in treating patients with bladder cancer undergoing surgery. Erlotinib hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
Detailed description
PRIMARY OBJECTIVES: I. To determine if there is a difference in EGFR phosphorylation in normal appearing bladder epithelium adjacent to tumor approximately 9-18 hours post-study dose, between patients randomized to erlotinib hydrochloride (erlotinib) weekly as compared to placebo. SECONDARY OBJECTIVES: I. Assess the tolerance of high dose weekly erlotinib compared to placebo. II. Assess the expression of phosphorylated EGF receptor in tumor tissue when available. III. Assess the expression of e-cadherin and Ki67 in normal and abnormal urothelium. IV. Assess the expression of phosphorylated ERK in normal and abnormal urothelium. V. Assess limited pharmacokinetics of weekly erlotinib. VI. Assess the expression of p53 in normal and abnormal urothelium. VII. Assess the expression of let-7 in normal and abnormal urothelium. VIII. Exploratory assessment of urination symptoms in men. OUTLINE: Patients are randomized to 1 of 2 treatment groups. GROUP I: Patients receive erlotinib hydrochloride orally (PO) once daily (QD) on days 1, 8, and 15. Patients then undergo transurethral resection of bladder tumor (TURBT) or cystectomy on day 16. GROUP II: Patients receive placebo PO QD on days 1, 8, and 15. Patients then undergo TURBT or cystectomy on day 16. After completion of study treatment, patients are followed up for 7-14 days.
Interventions
DRUGErlotinib Hydrochloride
Given PO
OTHERLaboratory Biomarker Analysis
Correlative studies
OTHERPharmacological Study
Correlative studies
OTHERPlacebo
Given PO
OTHERQuality-of-Life Assessment
Ancillary studies
PROCEDURETherapeutic Conventional Surgery
Undergo TURBT or cystectomy
Sponsors
National Cancer Institute (NCI)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Participants must have a confirmed or suspected invasive or non-invasive bladder tumor (initial or recurrent) discovered on cystoscopy or radiologic imaging performed within 120 days of randomization * Patients with muscle invasive bladder cancer (MIBC) must have never received and currently be ineligible for cisplatin-based neoadjuvant chemotherapy due to any of the following: * Calculated creatinine clearance of \< 60 ml/min * Karnofsky performance status (KPS) \< 80 * Solitary kidney or * Patient refusal to undergo neoadjuvant chemotherapy * The participant may have prior treatment for bladder tumor (excluding radiation therapy) provided that treatment: * Was completed greater than 30 days prior to the first dose of study agent * Participants must be a candidate for a trans-urethral resection of the bladder tumor (TURBT), cystectomy (partial or radical) or cystoscopy with biopsy at a participating organization * Karnofsky \>= 60% * White blood cells (WBC) \>= 3000/mm\^3 * Platelets \>= 100,000mm\^3 * Hemoglobin \> 10 g/dL * Alkaline phosphatase =\< 1.5 x upper limit of normal * Bilirubin =\< 1.5 x upper limit of normal * Aspartate aminotransferase (AST) =\< 1.5 x upper limit of normal * Alanine aminotransferase (ALT) =\< 1.5 x upper limit of normal * Bilirubin for Gilbert's =\< 3.0 mg/dl * A calculated creatinine clearance (Cockcroft Gault) of \>= 30 ml/min * Sodium \>= 130 mg/dl and =\< upper limit of normal * Potassium \>= 3.0 mg/dl and =\< upper limit of normal * Women of child-bearing potential and men 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; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her study physician immediately * Ability to understand and the willingness to sign a written informed consent document
Exclusion criteria
* Any treatment for the bladder tumor other than intravesical therapy between the pre-study cystoscopy or radiologic imaging which identified the suspected bladder tumor and the scheduled surgical removal or cystoscopy-guided biopsy of that tumor * Any chemotherapy and/or radiation therapy received =\< 3 months of study entry and any immunotherapy received =\< 6 months of study entry (with the exception of Bacillus Calmette-Guerin \[BCG\] treatment) * Any prior external beam radiation to the pelvis * A concurrent skin rash or skin condition requiring treatment with a prescription medication * The following medications may not be taken within 24 hours of the first dose of study agent or at any time while a participant is taking study agent * Coumadin * Strong CYP3A4 inhibitors including ketoconazole, atazanavir, boceprevir, ceritinib, clarithromycin, cobicistat, darunavir, dasabuvir, idelalisib, indinavir, itraconazole, lopinavir, nefazodone, nelfinavir, ombitasvir, paritaprevir, posaconazole, ritonavir, saquinavir, telithromycin, troleandomycin, voriconazole, and grapefruit or grapefruit juice * CYP3A4 inducers including rifampicin, rifabutin, rifapentine, phenytoin, carbamazepine, phenobarbital, primidone, enzalutamide, fosphenytoin, lumacaftor, mitotane, and St. John's wort * Agents which decrease gastric acid are allowed but should be avoided if possible * Participants may resume inhibitors or inducers of CYP3A4 \> 14 days after their last dose of study agent * Participants requiring daily use of non-steroidal anti-inflammatory drugs (NSAIDs), with the exception of =\< 81 mg aspirin per day; during study participation, acetaminophen is preferred for treatment of pain; the use of NSAIDs, as needed for pain, is discouraged * Participants may not be receiving any other investigational agents * History of allergic reactions attributed to compounds of similar chemical or biologic composition to erlotinib or clindamycin (topical agent for potential skin toxicity) * An underlying predisposition to rectal or gastrointestinal bleeding or uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements * Females who are pregnant or lactating may not participate in this study; females of child-bearing potential must have a negative pregnancy test before starting study agent; patients who have had a bilateral oophorectomy, hysterectomy, or are greater than 1 year since their last menses are not considered to be of child-bearing potential
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| EGFR Phosphorylation in Normal Appearing Bladder Epithelium Adjacent to Tumor | Up to 18 hours after last study drug dose (on day 28) | EGFR phosphorylation will be assessed using Immunohistochemistry (IHC), greater mean optical density is associated with greater phosphorylation. The difference between the placebo group and the erlotinib hydrochloride group will be tested as-randomized using a two-sample t-test with normalizing transformation if necessary or Wilcoxon rank-sum test. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetic Parameters: Erlotinib in Blood | Baseline, day 8, and day 16 (day of surgery) | Will be summarized by treatment arm (and, if applicable, by visit) with appropriate descriptive statistics. |
| Pharmacokinetic Parameters: OSI-420 in Blood | Baseline, day 8, and day 16 (day of surgery) | Will be summarized by treatment arm (and, if applicable, by visit) with appropriate descriptive statistics. |
| Frequency of Urination Symptoms in Men Only, Graded According to International Prostate Symptom Score (I-PSS) | Baseline up to 18 hours after last study drug dose (on day 28) | A well documented survey called the International Prostate Symptom Score (I-PSS) of urination symptoms which correlates with prostatic hyperplasia in men will be filled out by men at baseline and end of study. The I-PSS is an 8-item survey; 7 questions scored from 0-5 where 0 is 'none' or 'not at all' and 5 is 'five times' or 'almost always'. The sum of the scores for the first 7 questions has a total range of 0-35 where 0 is asymptomatic, 1-7 is mild symptoms, 8-19 is moderate symptoms, and 20-35 are severe symptoms. A final quality of life question is scored from 0-6 where 0 (delighted) to 6 (terrible). This question serves as a conversation starting point between the patient and physician. |
| Expression of E-cadherin | At time of surgery (approximately day 16) | E-Cadherin expression will be assessed using Immunohistochemistry (IHC), greater membrane optical density was associated with greater expression. A two-sample t-test with normalizing transformation if necessary or Wilcoxon rank-sum test will be used. |
| EGFR Phosphorylation in Neoplastic Bladder Epithelium 9-18 Hours Post-study Dose | Up to 18 hours after last study drug dose (on day 28) | EGFR phosphorylation will be assessed using Immunohistochemistry (IHC), greater mean optical density is associated with greater phosphorylation. |
| Difference Between Normal and Neoplastic Tissue Phosphorylated ERK | At time of surgery (approximately day 16) | Phosphorylated ERK will be assessed using Immunohistochemistry (IHC), greater mean optical density is associated with greater expression. A two-sample t-test with normalizing transformation if necessary or Wilcoxon rank-sum test will be used. |
| Difference Between Normal and Neoplastic Tissue of p53 | At time of surgery (approximately day 16) | p53 expression will be assessed using Immunohistochemistry (IHC), greater nucleus optical density and positivity was associated with greater expression. A two-sample t-test with normalizing transformation if necessary or Wilcoxon rank-sum test will be used. |
| Difference Between Normal and Neoplastic Tissue of Let-7 | At time of surgery (approximately day 16) | A two-sample t-test with normalizing transformation if necessary or Wilcoxon rank-sum test will be used. |
| Percentage of Cells Expressing Ki67 | At time of surgery (approximately day 16) | Ki-67 expression will be assessed using Immunohistochemistry (IHC), greater positivity was associated with greater expression. A two-sample t-test with normalizing transformation if necessary or Wilcoxon rank-sum test will be used. |
Countries
United States
Participant flow
Pre-assignment details
50 were consented, 13 participants ineligible
Participants by arm
| Arm | Count |
|---|---|
| Group I (Erlotinib Hydrochloride) Participants receive erlotinib hydrochloride PO QD on days 1, 8, and 15. Participants then undergo TURBT or cystectomy on day 16. | 24 |
| Group II (Placebo) Participants receive placebo PO QD on days 1, 8, and 15. Participants then undergo TURBT or cystectomy on day 16. | 13 |
| Total | 37 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Physician Decision | 0 | 1 |
Baseline characteristics
| Characteristic | Total | Group I (Erlotinib Hydrochloride) | Group II (Placebo) |
|---|---|---|---|
| Age, Customized Participant Age | 69.93 years | 70.25 years | 69.32 years |
| Body Mass Index | 28.96 kg/m^2 | 29.37 kg/m^2 | 28.25 kg/m^2 |
| Current Smoker No | 28 Participants | 18 Participants | 10 Participants |
| Current Smoker Yes | 9 Participants | 6 Participants | 3 Participants |
| Diastolic Blood Pressure | 77.19 mmHg | 76.62 mmHg | 78.23 mmHg |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants | 1 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 34 Participants | 23 Participants | 11 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Ever Smoked No | 5 Participants | 3 Participants | 2 Participants |
| Ever Smoked Yes | 32 Participants | 21 Participants | 11 Participants |
| Height | 174.64 cm | 174.77 cm | 174.40 cm |
| Karnofsky Performance Status 100 | 29 Participants | 19 Participants | 10 Participants |
| Karnofsky Performance Status 80 | 1 Participants | 1 Participants | 0 Participants |
| Karnofsky Performance Status 90 | 7 Participants | 4 Participants | 3 Participants |
| Medical History / Baseline Presence of Abnormality or Disease Abdomen | 1 participants | 1 participants | 0 participants |
| Medical History / Baseline Presence of Abnormality or Disease Appearance | 1 participants | 0 participants | 1 participants |
| Medical History / Baseline Presence of Abnormality or Disease Breasts | 0 participants | 0 participants | 0 participants |
| Medical History / Baseline Presence of Abnormality or Disease Chest | 0 participants | 0 participants | 0 participants |
| Medical History / Baseline Presence of Abnormality or Disease Genitalia | 3 participants | 1 participants | 2 participants |
| Medical History / Baseline Presence of Abnormality or Disease Head, Eyes, Ears, Nose, Throat | 1 participants | 1 participants | 0 participants |
| Medical History / Baseline Presence of Abnormality or Disease Heart | 1 participants | 1 participants | 0 participants |
| Medical History / Baseline Presence of Abnormality or Disease Lungs | 1 participants | 1 participants | 0 participants |
| Medical History / Baseline Presence of Abnormality or Disease Lymph Nodes | 0 participants | 0 participants | 0 participants |
| Medical History / Baseline Presence of Abnormality or Disease Musculoskeletal | 2 participants | 2 participants | 0 participants |
| Medical History / Baseline Presence of Abnormality or Disease Neurologic | 0 participants | 0 participants | 0 participants |
| Medical History / Baseline Presence of Abnormality or Disease Pelvis | 0 participants | 0 participants | 0 participants |
| Medical History / Baseline Presence of Abnormality or Disease Prostate | 3 participants | 2 participants | 1 participants |
| Medical History / Baseline Presence of Abnormality or Disease Rectal | 0 participants | 0 participants | 0 participants |
| Medical History / Baseline Presence of Abnormality or Disease Skin | 2 participants | 2 participants | 0 participants |
| Medical History / Baseline Presence of Abnormality or Disease Thyroid | 0 participants | 0 participants | 0 participants |
| Medical History / Baseline Presence of Abnormality or Disease Vascular | 1 participants | 1 participants | 0 participants |
| Pulse | 73.03 beats per minute | 74.75 beats per minute | 69.85 beats per minute |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 2 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 35 Participants | 22 Participants | 13 Participants |
| Region of Enrollment United States | 37 participants | 24 participants | 13 participants |
| Sex: Female, Male Female | 6 Participants | 3 Participants | 3 Participants |
| Sex: Female, Male Male | 31 Participants | 21 Participants | 10 Participants |
| Systolic Blood Pressure | 135.35 mmHg | 134.62 mmHg | 136.69 mmHg |
| Temperature | 97.61 degrees Fahrenheit | 97.67 degrees Fahrenheit | 97.48 degrees Fahrenheit |
| Weight | 88.67 kg | 89.67 kg | 86.83 kg |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 24 | 0 / 13 |
| other Total, other adverse events | 22 / 24 | 8 / 13 |
| serious Total, serious adverse events | 1 / 24 | 2 / 13 |
Outcome results
Primary
EGFR Phosphorylation in Normal Appearing Bladder Epithelium Adjacent to Tumor
EGFR phosphorylation will be assessed using Immunohistochemistry (IHC), greater mean optical density is associated with greater phosphorylation. The difference between the placebo group and the erlotinib hydrochloride group will be tested as-randomized using a two-sample t-test with normalizing transformation if necessary or Wilcoxon rank-sum test.
Time frame: Up to 18 hours after last study drug dose (on day 28)
Population: Number analyzed differs from number of participants in each arm for two reasons: sample size insufficient for analysis and sample not obtained.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group I (Erlotinib Hydrochloride) | EGFR Phosphorylation in Normal Appearing Bladder Epithelium Adjacent to Tumor | Nucleus P-EGFR in Benign Tissue | 0.216 optical density | Standard Deviation 0.063 |
| Group I (Erlotinib Hydrochloride) | EGFR Phosphorylation in Normal Appearing Bladder Epithelium Adjacent to Tumor | Cytoplasm P-EGFR in Benign Tissue | 0.159 optical density | Standard Deviation 0.046 |
| Group I (Erlotinib Hydrochloride) | EGFR Phosphorylation in Normal Appearing Bladder Epithelium Adjacent to Tumor | Membrane P-EGFR in Benign Tissue | 0.179 optical density | Standard Deviation 0.053 |
| Group I (Erlotinib Hydrochloride) | EGFR Phosphorylation in Normal Appearing Bladder Epithelium Adjacent to Tumor | Entire Cell P-EGFR in Benign Tissue | 0.190 optical density | Standard Deviation 0.054 |
| Group II (Placebo) | EGFR Phosphorylation in Normal Appearing Bladder Epithelium Adjacent to Tumor | Entire Cell P-EGFR in Benign Tissue | 0.159 optical density | Standard Deviation 0.069 |
| Group II (Placebo) | EGFR Phosphorylation in Normal Appearing Bladder Epithelium Adjacent to Tumor | Nucleus P-EGFR in Benign Tissue | 0.181 optical density | Standard Deviation 0.073 |
| Group II (Placebo) | EGFR Phosphorylation in Normal Appearing Bladder Epithelium Adjacent to Tumor | Membrane P-EGFR in Benign Tissue | 0.148 optical density | Standard Deviation 0.074 |
| Group II (Placebo) | EGFR Phosphorylation in Normal Appearing Bladder Epithelium Adjacent to Tumor | Cytoplasm P-EGFR in Benign Tissue | 0.133 optical density | Standard Deviation 0.062 |
Comparison: Nucleus P-EGFR in benign tissue between erlotinib and placebop-value: 0.208Wilcoxon rank-sum test
Comparison: Cytoplasm P-EGFR in benign tissue between erlotinib and placebop-value: 0.208Wilcoxon rank-sum test
Comparison: Membrane P-EGFR in benign tissue between erlotinib and placebop-value: 0.272Wilcoxon rank-sum test
Comparison: Entire Cell P-EGFR in benign tissue between erlotinib and placebop-value: 0.22Wilcoxon rank-sum test
Secondary
Difference Between Normal and Neoplastic Tissue of Let-7
A two-sample t-test with normalizing transformation if necessary or Wilcoxon rank-sum test will be used.
Time frame: At time of surgery (approximately day 16)
Population: This analysis was not completed after discussions with DCP. Participant samples were rationed for multiple analyses, Let-7 analysis was determined to be low on the priority list and it was decided to forego this analysis.
Secondary
Difference Between Normal and Neoplastic Tissue of p53
p53 expression will be assessed using Immunohistochemistry (IHC), greater nucleus optical density and positivity was associated with greater expression. A two-sample t-test with normalizing transformation if necessary or Wilcoxon rank-sum test will be used.
Time frame: At time of surgery (approximately day 16)
Population: Number analyzed differs from number of participants in each arm for two reasons: sample size insufficient for analysis and sample not obtained. As well as there was not enough tissue to complete this analysis for all participants.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Group I (Erlotinib Hydrochloride) | Difference Between Normal and Neoplastic Tissue of p53 | -0.052 Optical Density (OD) | Standard Deviation 0.185 |
| Group II (Placebo) | Difference Between Normal and Neoplastic Tissue of p53 | -0.115 Optical Density (OD) | Standard Deviation 0.305 |
p-value: 0.772Wilcoxon rank-sum test
Secondary
Difference Between Normal and Neoplastic Tissue Phosphorylated ERK
Phosphorylated ERK will be assessed using Immunohistochemistry (IHC), greater mean optical density is associated with greater expression. A two-sample t-test with normalizing transformation if necessary or Wilcoxon rank-sum test will be used.
Time frame: At time of surgery (approximately day 16)
Population: Number analyzed differs from number of participants in each arm for two reasons: sample size insufficient for analysis and sample not obtained.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group I (Erlotinib Hydrochloride) | Difference Between Normal and Neoplastic Tissue Phosphorylated ERK | Nucleus P-ERK Normal-Tumor | -0.071 Optical Density (OD) | Standard Deviation 0.167 |
| Group I (Erlotinib Hydrochloride) | Difference Between Normal and Neoplastic Tissue Phosphorylated ERK | Cytoplasm P-ERK Normal-Tumor | -0.104 Optical Density (OD) | Standard Deviation 0.187 |
| Group I (Erlotinib Hydrochloride) | Difference Between Normal and Neoplastic Tissue Phosphorylated ERK | Entire Cell P-ERK Normal-Tumor | -0.084 Optical Density (OD) | Standard Deviation 0.171 |
| Group II (Placebo) | Difference Between Normal and Neoplastic Tissue Phosphorylated ERK | Nucleus P-ERK Normal-Tumor | -0.077 Optical Density (OD) | Standard Deviation 0.183 |
| Group II (Placebo) | Difference Between Normal and Neoplastic Tissue Phosphorylated ERK | Cytoplasm P-ERK Normal-Tumor | -0.098 Optical Density (OD) | Standard Deviation 0.17 |
| Group II (Placebo) | Difference Between Normal and Neoplastic Tissue Phosphorylated ERK | Entire Cell P-ERK Normal-Tumor | -0.085 Optical Density (OD) | Standard Deviation 0.173 |
Comparison: Difference in p-ERK between Normal and Tumor Tissue, P-Value between armsp-value: 1Wilcoxon rank-sum test
Comparison: Difference in Cytoplasm p-ERK between Normal and Tumor Tissue, P-Value between armsp-value: 0.792Wilcoxon rank-sum test
Comparison: Difference in Entire Cell p-ERK between Normal and Tumor Tissue, p-value between armsp-value: 1Wilcoxon rank-sum test
Secondary
EGFR Phosphorylation in Neoplastic Bladder Epithelium 9-18 Hours Post-study Dose
EGFR phosphorylation will be assessed using Immunohistochemistry (IHC), greater mean optical density is associated with greater phosphorylation.
Time frame: Up to 18 hours after last study drug dose (on day 28)
Population: Number analyzed differs from number of participants in each arm for two reasons: sample size insufficient for analysis and sample not obtained.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group I (Erlotinib Hydrochloride) | EGFR Phosphorylation in Neoplastic Bladder Epithelium 9-18 Hours Post-study Dose | Nucleus P-EGFR Tumor Tissue | 0.175 Optical Density (OD) | Standard Deviation 0.06 |
| Group I (Erlotinib Hydrochloride) | EGFR Phosphorylation in Neoplastic Bladder Epithelium 9-18 Hours Post-study Dose | Cytoplasm P-EGFR Tumor Tissue | 0.161 Optical Density (OD) | Standard Deviation 0.053 |
| Group I (Erlotinib Hydrochloride) | EGFR Phosphorylation in Neoplastic Bladder Epithelium 9-18 Hours Post-study Dose | Membrane P-EGFR Tumor Tissue | 0.170 Optical Density (OD) | Standard Deviation 0.058 |
| Group I (Erlotinib Hydrochloride) | EGFR Phosphorylation in Neoplastic Bladder Epithelium 9-18 Hours Post-study Dose | Entire Cell P-EGFR Tumor Tissue | 0.170 Optical Density (OD) | Standard Deviation 0.056 |
| Group II (Placebo) | EGFR Phosphorylation in Neoplastic Bladder Epithelium 9-18 Hours Post-study Dose | Entire Cell P-EGFR Tumor Tissue | 0.151 Optical Density (OD) | Standard Deviation 0.061 |
| Group II (Placebo) | EGFR Phosphorylation in Neoplastic Bladder Epithelium 9-18 Hours Post-study Dose | Nucleus P-EGFR Tumor Tissue | 0.155 Optical Density (OD) | Standard Deviation 0.059 |
| Group II (Placebo) | EGFR Phosphorylation in Neoplastic Bladder Epithelium 9-18 Hours Post-study Dose | Membrane P-EGFR Tumor Tissue | 0.154 Optical Density (OD) | Standard Deviation 0.072 |
| Group II (Placebo) | EGFR Phosphorylation in Neoplastic Bladder Epithelium 9-18 Hours Post-study Dose | Cytoplasm P-EGFR Tumor Tissue | 0.146 Optical Density (OD) | Standard Deviation 0.07 |
Comparison: Nucleus P-EGFR in Tumor Tissue, p-value between placebo and Erlotinibp-value: 0.361Wilcoxon rank-sum test
Comparison: Cytoplasm P-EGFR in Tumor Tissue, p-value between placebo and Erlotinibp-value: 0.383Wilcoxon rank-sum test
Comparison: Membrane P-EGFR in Tumor Tissue, p-value between placebo and Erlotinibp-value: 0.427Wilcoxon rank-sum test
Comparison: Entire Cell P-EGFR in Tumor Tissue, p-value between placebo and Erlotinibp-value: 0.416Wilcoxon rank-sum test
Secondary
Expression of E-cadherin
E-Cadherin expression will be assessed using Immunohistochemistry (IHC), greater membrane optical density was associated with greater expression. A two-sample t-test with normalizing transformation if necessary or Wilcoxon rank-sum test will be used.
Time frame: At time of surgery (approximately day 16)
Population: Number analyzed differs from number of participants in each arm for two reasons: sample size insufficient for analysis and sample not obtained.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group I (Erlotinib Hydrochloride) | Expression of E-cadherin | Benign Tissue | 0.615 Optical Density (OD) | Standard Deviation 0.126 |
| Group I (Erlotinib Hydrochloride) | Expression of E-cadherin | Tumor Tissue | 0.616 Optical Density (OD) | Standard Deviation 0.07 |
| Group II (Placebo) | Expression of E-cadherin | Benign Tissue | 0.572 Optical Density (OD) | Standard Deviation 0.198 |
| Group II (Placebo) | Expression of E-cadherin | Tumor Tissue | 0.563 Optical Density (OD) | Standard Deviation 0.079 |
Comparison: Expression of e-cadherin in Benign Tissue, P-Value between armsp-value: 0.721Wilcoxon rank-sum test
Comparison: Expression of e-cadherin in Tumor Tissue, P-Value between armsp-value: 0.108Wilcoxon rank-sum test
Secondary
Frequency of Urination Symptoms in Men Only, Graded According to International Prostate Symptom Score (I-PSS)
A well documented survey called the International Prostate Symptom Score (I-PSS) of urination symptoms which correlates with prostatic hyperplasia in men will be filled out by men at baseline and end of study. The I-PSS is an 8-item survey; 7 questions scored from 0-5 where 0 is 'none' or 'not at all' and 5 is 'five times' or 'almost always'. The sum of the scores for the first 7 questions has a total range of 0-35 where 0 is asymptomatic, 1-7 is mild symptoms, 8-19 is moderate symptoms, and 20-35 are severe symptoms. A final quality of life question is scored from 0-6 where 0 (delighted) to 6 (terrible). This question serves as a conversation starting point between the patient and physician.
Time frame: Baseline up to 18 hours after last study drug dose (on day 28)
Population: A participant in the placebo group had no survey response at baseline.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Group I (Erlotinib Hydrochloride) | Frequency of Urination Symptoms in Men Only, Graded According to International Prostate Symptom Score (I-PSS) | Baseline | Severe (score of 20-35) | 1 Participants |
| Group I (Erlotinib Hydrochloride) | Frequency of Urination Symptoms in Men Only, Graded According to International Prostate Symptom Score (I-PSS) | Surgery Visit | Mild (score of 1-7) | 7 Participants |
| Group I (Erlotinib Hydrochloride) | Frequency of Urination Symptoms in Men Only, Graded According to International Prostate Symptom Score (I-PSS) | Surgery Visit | Moderate (score of 8-19) | 7 Participants |
| Group I (Erlotinib Hydrochloride) | Frequency of Urination Symptoms in Men Only, Graded According to International Prostate Symptom Score (I-PSS) | Baseline | Mild (score of 1-7) | 7 Participants |
| Group I (Erlotinib Hydrochloride) | Frequency of Urination Symptoms in Men Only, Graded According to International Prostate Symptom Score (I-PSS) | Surgery Visit | Severe (score of 20-35) | 1 Participants |
| Group I (Erlotinib Hydrochloride) | Frequency of Urination Symptoms in Men Only, Graded According to International Prostate Symptom Score (I-PSS) | Baseline | Moderate (score of 8-19) | 7 Participants |
| Group II (Placebo) | Frequency of Urination Symptoms in Men Only, Graded According to International Prostate Symptom Score (I-PSS) | Surgery Visit | Severe (score of 20-35) | 0 Participants |
| Group II (Placebo) | Frequency of Urination Symptoms in Men Only, Graded According to International Prostate Symptom Score (I-PSS) | Baseline | Mild (score of 1-7) | 3 Participants |
| Group II (Placebo) | Frequency of Urination Symptoms in Men Only, Graded According to International Prostate Symptom Score (I-PSS) | Baseline | Severe (score of 20-35) | 0 Participants |
| Group II (Placebo) | Frequency of Urination Symptoms in Men Only, Graded According to International Prostate Symptom Score (I-PSS) | Surgery Visit | Mild (score of 1-7) | 5 Participants |
| Group II (Placebo) | Frequency of Urination Symptoms in Men Only, Graded According to International Prostate Symptom Score (I-PSS) | Surgery Visit | Moderate (score of 8-19) | 2 Participants |
| Group II (Placebo) | Frequency of Urination Symptoms in Men Only, Graded According to International Prostate Symptom Score (I-PSS) | Baseline | Moderate (score of 8-19) | 3 Participants |
Comparison: P-value between groups at Baselinep-value: 0.792Wilcoxon rank-sum test
Comparison: P-value between groups at surgery visitp-value: 0.261Wilcoxon rank-sum test
Secondary
Percentage of Cells Expressing Ki67
Ki-67 expression will be assessed using Immunohistochemistry (IHC), greater positivity was associated with greater expression. A two-sample t-test with normalizing transformation if necessary or Wilcoxon rank-sum test will be used.
Time frame: At time of surgery (approximately day 16)
Population: Number analyzed differs from number of participants in each arm for two reasons: sample size insufficient for analysis and sample not obtained.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group I (Erlotinib Hydrochloride) | Percentage of Cells Expressing Ki67 | Benign Tissue | 0.093 percentage | Standard Deviation 0.142 |
| Group I (Erlotinib Hydrochloride) | Percentage of Cells Expressing Ki67 | Tumor Tissue | 0.148 percentage | Standard Deviation 0.142 |
| Group II (Placebo) | Percentage of Cells Expressing Ki67 | Benign Tissue | 0.080 percentage | Standard Deviation 0.111 |
| Group II (Placebo) | Percentage of Cells Expressing Ki67 | Tumor Tissue | 0.170 percentage | Standard Deviation 0.137 |
Comparison: Expression of KI-67 in Benign Tissue, P-Value between armsp-value: 0.444Wilcoxon rank-sum test
Comparison: Expression of KI-67 in Tumor Tissue, P-Value between armsp-value: 0.663Wilcoxon rank-sum test
Secondary
Pharmacokinetic Parameters: Erlotinib in Blood
Will be summarized by treatment arm (and, if applicable, by visit) with appropriate descriptive statistics.
Time frame: Baseline, day 8, and day 16 (day of surgery)
Population: Number analyzed differs from number of participants in each arm for two reasons: sample size insufficient for analysis and sample not obtained.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group I (Erlotinib Hydrochloride) | Pharmacokinetic Parameters: Erlotinib in Blood | Baseline | 0.0 ng/mL | Standard Deviation 0 |
| Group I (Erlotinib Hydrochloride) | Pharmacokinetic Parameters: Erlotinib in Blood | Day 8 | 169.7 ng/mL | Standard Deviation 581.3 |
| Group I (Erlotinib Hydrochloride) | Pharmacokinetic Parameters: Erlotinib in Blood | Day 16 (Surgery) | 2218.4 ng/mL | Standard Deviation 1096.1 |
| Group II (Placebo) | Pharmacokinetic Parameters: Erlotinib in Blood | Baseline | 0.0 ng/mL | Standard Deviation 0 |
| Group II (Placebo) | Pharmacokinetic Parameters: Erlotinib in Blood | Day 8 | 0.0 ng/mL | Standard Deviation 0 |
| Group II (Placebo) | Pharmacokinetic Parameters: Erlotinib in Blood | Day 16 (Surgery) | 0.3 ng/mL | Standard Deviation 1.2 |
Comparison: Baseline visit - p-value between erlotinib and placebo armsp-value: 1Wilcoxon rank-sum test
Comparison: Day 8 - p-value between erlotinib and placebo armsp-value: 0.199Wilcoxon rank-sum test
Comparison: Surgery visit - p-value between erlotinib and placebo armsp-value: <0.001Wilcoxon rank-sum test
Secondary
Pharmacokinetic Parameters: OSI-420 in Blood
Will be summarized by treatment arm (and, if applicable, by visit) with appropriate descriptive statistics.
Time frame: Baseline, day 8, and day 16 (day of surgery)
Population: Number analyzed differs from number of participants in each arm for two reasons: sample size insufficient for analysis and sample not obtained.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group I (Erlotinib Hydrochloride) | Pharmacokinetic Parameters: OSI-420 in Blood | Baseline | 0.0 ng/mL | Standard Deviation 0 |
| Group I (Erlotinib Hydrochloride) | Pharmacokinetic Parameters: OSI-420 in Blood | Day 8 | 2.5 ng/mL | Standard Deviation 7.3 |
| Group I (Erlotinib Hydrochloride) | Pharmacokinetic Parameters: OSI-420 in Blood | Day 16 (Surgery) | 44.4 ng/mL | Standard Deviation 34.6 |
| Group II (Placebo) | Pharmacokinetic Parameters: OSI-420 in Blood | Baseline | 0.0 ng/mL | Standard Deviation 0 |
| Group II (Placebo) | Pharmacokinetic Parameters: OSI-420 in Blood | Day 8 | 0.0 ng/mL | Standard Deviation 0 |
| Group II (Placebo) | Pharmacokinetic Parameters: OSI-420 in Blood | Day 16 (Surgery) | 0.0 ng/mL | Standard Deviation 0 |
Comparison: Baseline visit - p-value between erlotinib and placebo armsp-value: 1Wilcoxon rank-sum test
Comparison: Day 8 - p-value between erlotinib and placebo armsp-value: 0.288Wilcoxon rank-sum test
Comparison: Surgery visit - p-value between erlotinib and placebo armsp-value: <0.001Wilcoxon rank-sum test