NCT02169284

Erlotinib Hydrochloride in Treating Patients With Bladder Cancer Undergoing Surgery

Terminated Phase 2 Results posted Last updated 7 July 2020

What this trial tests

Phase 2 trial testing Erlotinib Hydrochloride in Bladder Carcinoma in 50 participants. Terminated before completion.

Timeline

1 October 2014

Primary endpoint
30 March 2018

30 March 2018

Quick facts

Lead sponsor	National Cancer Institute (NCI)
Phase	Phase 2
Status	Terminated
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	double
Primary purpose	treatment
Enrollment	50
Start date	1 October 2014
Primary completion	30 March 2018
Estimated completion	30 March 2018
Sites	6 locations across United States

Drugs / interventions tested

• Erlotinib Hydrochloride — full drug profile →
• Laboratory Biomarker Analysis — full drug profile →
• Pharmacological Study — full drug profile →
• Placebo
• Quality-of-Life Assessment
• Therapeutic Conventional Surgery

Conditions studied

• Bladder Carcinoma — all drugs for Bladder Carcinoma →
• Recurrent Bladder Carcinoma — all drugs for Recurrent Bladder Carcinoma →

Sponsor

National Cancer Institute (NCI)

Who can join

18 and older, any sex, with Bladder Carcinoma or Recurrent Bladder Carcinoma. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

EGFR Phosphorylation in Normal Appearing Bladder Epithelium Adjacent to Tumor Primary · 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.

Nucleus P-EGFR in Benign Tissue

Group	Value	95% CI
Group I (Erlotinib Hydrochloride)	0.216	± 0.063
Group II (Placebo)	0.181	± 0.073

Cytoplasm P-EGFR in Benign Tissue

Group	Value	95% CI
Group I (Erlotinib Hydrochloride)	0.159	± 0.046
Group II (Placebo)	0.133	± 0.062

Membrane P-EGFR in Benign Tissue

Group	Value	95% CI
Group I (Erlotinib Hydrochloride)	0.179	± 0.053
Group II (Placebo)	0.148	± 0.074

Entire Cell P-EGFR in Benign Tissue

Group	Value	95% CI
Group I (Erlotinib Hydrochloride)	0.190	± 0.054
Group II (Placebo)	0.159	± 0.069

EGFR Phosphorylation in Neoplastic Bladder Epithelium 9-18 Hours Post-study Dose Secondary · 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.

Nucleus P-EGFR Tumor Tissue

Group	Value	95% CI
Group I (Erlotinib Hydrochloride)	0.175	± 0.060
Group II (Placebo)	0.155	± 0.059

Cytoplasm P-EGFR Tumor Tissue

Group	Value	95% CI
Group I (Erlotinib Hydrochloride)	0.161	± 0.053
Group II (Placebo)	0.146	± 0.070

Membrane P-EGFR Tumor Tissue

Group	Value	95% CI
Group I (Erlotinib Hydrochloride)	0.170	± 0.058
Group II (Placebo)	0.154	± 0.072

Entire Cell P-EGFR Tumor Tissue

Group	Value	95% CI
Group I (Erlotinib Hydrochloride)	0.170	± 0.056
Group II (Placebo)	0.151	± 0.061

Pharmacokinetic Parameters: Erlotinib in Blood Secondary · Baseline, day 8, and day 16 (day of surgery)

Will be summarized by treatment arm (and, if applicable, by visit) with appropriate descriptive statistics.

Baseline

Group	Value	95% CI
Group I (Erlotinib Hydrochloride)	0.0	± 0.0
Group II (Placebo)	0.0	± 0.0

Day 8

Group	Value	95% CI
Group I (Erlotinib Hydrochloride)	169.7	± 581.3
Group II (Placebo)	0.0	± 0.0

Day 16 (Surgery)

Group	Value	95% CI
Group I (Erlotinib Hydrochloride)	2218.4	± 1096.1
Group II (Placebo)	0.3	± 1.2

Pharmacokinetic Parameters: OSI-420 in Blood Secondary · Baseline, day 8, and day 16 (day of surgery)

Will be summarized by treatment arm (and, if applicable, by visit) with appropriate descriptive statistics.

Baseline

Group	Value	95% CI
Group I (Erlotinib Hydrochloride)	0.0	± 0.0
Group II (Placebo)	0.0	± 0.0

Day 8

Group	Value	95% CI
Group I (Erlotinib Hydrochloride)	2.5	± 7.3
Group II (Placebo)	0.0	± 0.0

Day 16 (Surgery)

Group	Value	95% CI
Group I (Erlotinib Hydrochloride)	44.4	± 34.6
Group II (Placebo)	0.0	± 0.0

Frequency of Urination Symptoms in Men Only, Graded According to International Prostate Symptom Score (I-PSS) Secondary · 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

Baseline

Group	Value	95% CI
Group I (Erlotinib Hydrochloride)	7
Group II (Placebo)	3
Group I (Erlotinib Hydrochloride)	7
Group II (Placebo)	3
Group I (Erlotinib Hydrochloride)	1
Group II (Placebo)	0

Surgery Visit

Group	Value	95% CI
Group I (Erlotinib Hydrochloride)	7
Group II (Placebo)	5
Group I (Erlotinib Hydrochloride)	7
Group II (Placebo)	2
Group I (Erlotinib Hydrochloride)	1
Group II (Placebo)	0

Expression of E-cadherin Secondary · 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.

Benign Tissue

Group	Value	95% CI
Group I (Erlotinib Hydrochloride)	0.615	± 0.126
Group II (Placebo)	0.572	± 0.198

Tumor Tissue

Group	Value	95% CI
Group I (Erlotinib Hydrochloride)	0.616	± 0.070
Group II (Placebo)	0.563	± 0.079

Percentage of Cells Expressing Ki67 Secondary · 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.

Benign Tissue

Group	Value	95% CI
Group I (Erlotinib Hydrochloride)	0.093	± 0.142
Group II (Placebo)	0.080	± 0.111

Tumor Tissue

Group	Value	95% CI
Group I (Erlotinib Hydrochloride)	0.148	± 0.142
Group II (Placebo)	0.170	± 0.137

Difference Between Normal and Neoplastic Tissue Phosphorylated ERK Secondary · 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.

Nucleus P-ERK Normal-Tumor

Group	Value	95% CI
Group I (Erlotinib Hydrochloride)	-0.071	± 0.167
Group II (Placebo)	-0.077	± 0.183

Cytoplasm P-ERK Normal-Tumor

Group	Value	95% CI
Group I (Erlotinib Hydrochloride)	-0.104	± 0.187
Group II (Placebo)	-0.098	± 0.170

Entire Cell P-ERK Normal-Tumor

Group	Value	95% CI
Group I (Erlotinib Hydrochloride)	-0.084	± 0.171
Group II (Placebo)	-0.085	± 0.173

Difference Between Normal and Neoplastic Tissue of p53 Secondary · 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.

Group	Value	95% CI
Group I (Erlotinib Hydrochloride)	-0.052	± 0.185
Group II (Placebo)	-0.115	± 0.305

Adverse events — posted to ClinicalTrials.gov

Time frame: up to 9 weeks. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Group I (Erlotinib Hydrochloride)

Serious: 1/24 (4%)

Deaths: 0/24

Group II (Placebo)

Serious: 2/13 (15%)

Deaths: 0/13

Serious adverse events (2 terms)

Reaction	System	Group I (Erlotinib Hydroch…	Group II (Placebo)
Surgical and Medical Procedures, Other	Surgical and medical procedures	—	—
Lower Gastrointestinal Hemorrhage	Gastrointestinal disorders	—	—

Other adverse events (65 terms — click to expand)

Reaction	System	Group I (Erlotinib Hydroch…	Group II (Placebo)
Diarrhea	Gastrointestinal disorders	—	—
Hypertension	Vascular disorders	—	—
Rash Acneiform	Skin and subcutaneous tissue disorders	—	—
Pruritus	Skin and subcutaneous tissue disorders	—	—
Rash Maculo-Papular	Skin and subcutaneous tissue disorders	—	—
Urinary Tract Infection	Infections and infestations	—	—
Urinary Retention	Renal and urinary disorders	—	—
Skin and Subcuteaneous Tissue Disorders, Other	Skin and subcutaneous tissue disorders	—	—
Abdominal Pain	Gastrointestinal disorders	—	—
Fatigue	General disorders	—	—
Blood Bilirubin Increased	Investigations	—	—
Cognitive Disturbance	Nervous system disorders	—	—
Dizziness	Nervous system disorders	—	—
Headache	Nervous system disorders	—	—
Bladder Spasm	Renal and urinary disorders	—	—
Urinary Tract Pain	Renal and urinary disorders	—	—
Allergic Rhinitis	Respiratory, thoracic and mediastinal disorders	—	—
Sore Throat	Respiratory, thoracic and mediastinal disorders	—	—
Dry Skin	Skin and subcutaneous tissue disorders	—	—
Urticaria	Skin and subcutaneous tissue disorders	—	—
Surgical and Medical Procedures, Other	Surgical and medical procedures	—	—
Blood and Lymphatic System Disorders, Other	Blood and lymphatic system disorders	—	—
Leukocytosis	Blood and lymphatic system disorders	—	—
Lymph Node Pain	Blood and lymphatic system disorders	—	—
Tinnitus	Ear and labyrinth disorders	—	—
Endocrine Orders, Other	Endocrine disorders	—	—
Dry Eye	Eye disorders	—	—
Bloating	Gastrointestinal disorders	—	—
Dry Mouth	Gastrointestinal disorders	—	—
Dyspepsia	Gastrointestinal disorders	—	—
Gastroesophageal Reflux Disease	Gastrointestinal disorders	—	—
Gastrointestinal Disorders, Other	Gastrointestinal disorders	—	—
Gastrointestinal Pain	Gastrointestinal disorders	—	—
Lower Gastrointestinal Hemorrhage	Gastrointestinal disorders	—	—
Mucositis Oral	Gastrointestinal disorders	—	—
Nausea	Gastrointestinal disorders	—	—
Oral Pain	Gastrointestinal disorders	—	—
Vomiting	Gastrointestinal disorders	—	—
Infections and Infestations, Other	Infections and infestations	—	—
Bruising	Injury, poisoning and procedural complications	—	—

Most-reported serious reactions: Surgical and Medical Procedures, Other, Lower Gastrointestinal Hemorrhage.

Data from ClinicalTrials.gov NCT02169284 adverse events section.

Sponsor's own description

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.

Publications & conference data

3 peer-reviewed publications reference this trial (live from Europe PMC):

1. Sulforaphane for the chemoprevention of bladder cancer: molecular mechanism targeted approach.
   Leone A, Diorio G, Sexton W, Schell M, et al · · 2017 · cited 40× · PMID 28423681 · DOI 10.18632/oncotarget.16015
2. Identifying and Creating the Next Generation of Community-Based Cancer Prevention Studies: Summary of a National Cancer Institute Think Tank.
   McCaskill-Stevens W, Pearson DC, Kramer BS, Ford LG, et al · · 2017 · cited 9× · PMID 27965286 · DOI 10.1158/1940-6207.capr-16-0230
3. Phase II Clinical Chemoprevention Trial of Weekly Erlotinib before Bladder Cancer Surgery.
   Downs TM, Bailey HH, Lozar T, Schmitz NS, et al · · 2025 · cited 2× · PMID 39187984 · DOI 10.1158/1940-6207.capr-24-0194