Trial Outcomes & Findings for Erlotinib Before and After Surgery in Treating Patients With Muscle-Invasive Bladder Cancer (NCT NCT00380029)
NCT ID: NCT00380029
Last Updated: 2017-07-19
Results Overview
Determine the effect of neoadjuvant erlotinib hydrochloride on histopathological, molecular, and genetic correlates in patients undergoing radical cystectomy for muscle-invasive bladder cancer. Gene expression of pre-treatment and post-treatment tumor samples were analyzed to define molecular determinants of response or resistance to epidermal growth factor receptor (EGFR) inhibition. Both in vitro and in vivo EGFR-associated signatures were evaluated on pre-treatment bladder tumors. Candidate molecular determinants of sensitivity to EGFR inhibition were characterized and examined for their ability to predict sensitivity to EGFR inhibitors in vitro.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
27 participants
Primary outcome timeframe
4 weeks before treatment and 4 weeks post treatment
Results posted on
2017-07-19
Participant Flow
27 patients were screened, 23 patients were consented to the study; three of these patients were not subsequently enrolled due to ineligibility (1) and patient decision not to enroll in the trial (2).
Participant milestones
| Measure |
Erlotinib
erlotinib given before and after transurethral resection of a bladder tumor, TURBT
Erlotinib: Erlotinib will be given at a dose of 150 mg per day for 4 weeks before undergoing planned radical cystectomy. In addition, patients will continue on erlotinib daily at a dose of 150 mg per day (qd dosing) for up to 2 years after surgery (beginning within 12 weeks of surgery) or until evidence of disease recurrence or progression
Radical Cystectomy: Will occur 4 weeks prior to dosing with erlotinib
|
|---|---|
|
Overall Study
STARTED
|
20
|
|
Overall Study
COMPLETED
|
20
|
|
Overall Study
NOT COMPLETED
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Erlotinib Before and After Surgery in Treating Patients With Muscle-Invasive Bladder Cancer
Baseline characteristics by cohort
| Measure |
Erlotinib
n=20 Participants
erlotinib given before and after transurethral resection of a bladder tumor, TURBT
Erlotinib: Erlotinib will be given at a dose of 150 mg per day for 4 weeks before undergoing planned radical cystectomy. In addition, patients will continue on erlotinib daily at a dose of 150 mg per day (qd dosing) for up to 2 years after surgery (beginning within 12 weeks of surgery) or until evidence of disease recurrence or progression
Radical Cystectomy: Will occur 4 weeks prior to dosing with erlotinib
|
|---|---|
|
Age, Continuous
|
67.1 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
5 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
15 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
20 participants
n=5 Participants
|
|
Smoking Status
Current
|
7 Participants
n=5 Participants
|
|
Smoking Status
Former
|
10 Participants
n=5 Participants
|
|
Smoking Status
Never
|
3 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 4 weeks before treatment and 4 weeks post treatmentPopulation: Only patients with tumor samples with sufficient and high quality RNA were used to generate the in vivo signatures.
Determine the effect of neoadjuvant erlotinib hydrochloride on histopathological, molecular, and genetic correlates in patients undergoing radical cystectomy for muscle-invasive bladder cancer. Gene expression of pre-treatment and post-treatment tumor samples were analyzed to define molecular determinants of response or resistance to epidermal growth factor receptor (EGFR) inhibition. Both in vitro and in vivo EGFR-associated signatures were evaluated on pre-treatment bladder tumors. Candidate molecular determinants of sensitivity to EGFR inhibition were characterized and examined for their ability to predict sensitivity to EGFR inhibitors in vitro.
Outcome measures
| Measure |
Downstaged Tumors
n=6 Participants
transurethral resection of a bladder tumor, (TURBT) tumors resected from participants treated with neo-adjuvant erlotinib which were considered to be downstaged ( pathologic tumor stage at cystectomy \<pT2 and N0)
|
Not-downstaged
n=15 Participants
transurethral resection of a bladder tumor, (TURBT) tumors resected from participants treated with neo-adjuvant erlotinib which were considered to be not-downstaged ( pathologic stage at cystectomy \>=pT2 or node positive (N1 or N2))
|
|---|---|---|
|
EGFR Activation Signal (AKT2) Expression to Predict Sensitivity to Erlotinib
|
-0.29 fold change
Interval -0.78 to 0.04
|
0.128 fold change
Interval -0.61 to 0.75
|
SECONDARY outcome
Timeframe: 4 weeksDetermine the pathological complete response rate (P0 rate) after undergoing radical cystectomy (RC). Evaluated using Response Evaluation Criteria In Solid Tumors (RECIST). Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
Outcome measures
| Measure |
Downstaged Tumors
n=20 Participants
transurethral resection of a bladder tumor, (TURBT) tumors resected from participants treated with neo-adjuvant erlotinib which were considered to be downstaged ( pathologic tumor stage at cystectomy \<pT2 and N0)
|
Not-downstaged
transurethral resection of a bladder tumor, (TURBT) tumors resected from participants treated with neo-adjuvant erlotinib which were considered to be not-downstaged ( pathologic stage at cystectomy \>=pT2 or node positive (N1 or N2))
|
|---|---|---|
|
Pathological Complete Response Rate
|
5 Participants
|
—
|
SECONDARY outcome
Timeframe: 2 yearsTo determine disease recurrence/progression rates after cystectomy in patients treated with erlotinib
Outcome measures
| Measure |
Downstaged Tumors
n=20 Participants
transurethral resection of a bladder tumor, (TURBT) tumors resected from participants treated with neo-adjuvant erlotinib which were considered to be downstaged ( pathologic tumor stage at cystectomy \<pT2 and N0)
|
Not-downstaged
transurethral resection of a bladder tumor, (TURBT) tumors resected from participants treated with neo-adjuvant erlotinib which were considered to be not-downstaged ( pathologic stage at cystectomy \>=pT2 or node positive (N1 or N2))
|
|---|---|---|
|
Disease Recurrence and Progression Rates After Cystectomy
|
4 Participants
|
—
|
SECONDARY outcome
Timeframe: 25 monthsThe number of patients who remained alive and with no evidence of disease at the mean (range) follow-up of 24.8 months (3.0-36.6).
Outcome measures
| Measure |
Downstaged Tumors
n=20 Participants
transurethral resection of a bladder tumor, (TURBT) tumors resected from participants treated with neo-adjuvant erlotinib which were considered to be downstaged ( pathologic tumor stage at cystectomy \<pT2 and N0)
|
Not-downstaged
transurethral resection of a bladder tumor, (TURBT) tumors resected from participants treated with neo-adjuvant erlotinib which were considered to be not-downstaged ( pathologic stage at cystectomy \>=pT2 or node positive (N1 or N2))
|
|---|---|---|
|
Overall Survival Rate
|
10 Participants
|
—
|
SECONDARY outcome
Timeframe: 4 weeks - 2 years following surgeryPopulation: All patients enrolled received the full 4-week neoadjuvant course of erlotinib. 12 patients continued on erlotinib in the adjuvant phase for a mean (range) duration of 29 (5-84) weeks.
The incidence of all toxicities observed during neoadjuvant and adjuvant treatment phase.Toxicity will be graded per the Common Terminology Criteria for Adverse Events (CTCAE) 2.0.
Outcome measures
| Measure |
Downstaged Tumors
n=20 Participants
transurethral resection of a bladder tumor, (TURBT) tumors resected from participants treated with neo-adjuvant erlotinib which were considered to be downstaged ( pathologic tumor stage at cystectomy \<pT2 and N0)
|
Not-downstaged
n=12 Participants
transurethral resection of a bladder tumor, (TURBT) tumors resected from participants treated with neo-adjuvant erlotinib which were considered to be not-downstaged ( pathologic stage at cystectomy \>=pT2 or node positive (N1 or N2))
|
|---|---|---|
|
Number of Subjects Experiencing Adverse Events
Rash
|
15 Participants
|
6 Participants
|
|
Number of Subjects Experiencing Adverse Events
Anorexia
|
6 Participants
|
0 Participants
|
|
Number of Subjects Experiencing Adverse Events
Diarrea
|
6 Participants
|
1 Participants
|
|
Number of Subjects Experiencing Adverse Events
Fatigue
|
6 Participants
|
2 Participants
|
|
Number of Subjects Experiencing Adverse Events
Lower urinary tract symptoms
|
4 Participants
|
0 Participants
|
|
Number of Subjects Experiencing Adverse Events
Nausea
|
3 Participants
|
0 Participants
|
|
Number of Subjects Experiencing Adverse Events
Cough
|
3 Participants
|
2 Participants
|
|
Number of Subjects Experiencing Adverse Events
Dry skin
|
2 Participants
|
1 Participants
|
|
Number of Subjects Experiencing Adverse Events
Haematuria
|
2 Participants
|
0 Participants
|
|
Number of Subjects Experiencing Adverse Events
Vagal episode
|
1 Participants
|
1 Participants
|
|
Number of Subjects Experiencing Adverse Events
Stomatitus
|
1 Participants
|
2 Participants
|
|
Number of Subjects Experiencing Adverse Events
Pneumonitis
|
0 Participants
|
1 Participants
|
|
Number of Subjects Experiencing Adverse Events
Deep vein thrombosis
|
0 Participants
|
1 Participants
|
Adverse Events
Erlotinib
Serious events: 8 serious events
Other events: 23 other events
Deaths: 11 deaths
Serious adverse events
| Measure |
Erlotinib
n=23 participants at risk
erlotinib given before and after transurethral resection of a bladder tumor, TURBT
Erlotinib: Erlotinib will be given at a dose of 150 mg per day for 4 weeks before undergoing planned radical cystectomy. In addition, patients will continue on erlotinib daily at a dose of 150 mg per day (qd dosing) for up to 2 years after surgery (beginning within 12 weeks of surgery) or until evidence of disease recurrence or progression
Radical Cystectomy: Will occur 4 weeks prior to dosing with erlotinib
|
|---|---|
|
Cardiac disorders
Cardiac ischemia/infarction
|
8.7%
2/23 • 5 years
|
|
Cardiac disorders
Cardiovascular/Arrhythmia-Other (Abnormal EKG)
|
4.3%
1/23 • 5 years
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
4.3%
1/23 • 5 years
|
|
General disorders
Death NOS- Unknown cause
|
4.3%
1/23 • 5 years
|
|
Gastrointestinal disorders
Gastrointestinal-Other (Mallory-Weiss tear w/nausea, vomiting)
|
4.3%
1/23 • 5 years
|
|
Gastrointestinal disorders
Ileus (or neuroconstipation)
|
8.7%
2/23 • 5 years
|
|
Infections and infestations
Infection without neutropenia
|
4.3%
1/23 • 5 years
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal- Other (Parastomal hernia)
|
4.3%
1/23 • 5 years
|
|
Injury, poisoning and procedural complications
Thrombosis/embolism
|
8.7%
2/23 • 5 years
|
|
Nervous system disorders
Syncope
|
4.3%
1/23 • 5 years
|
Other adverse events
| Measure |
Erlotinib
n=23 participants at risk
erlotinib given before and after transurethral resection of a bladder tumor, TURBT
Erlotinib: Erlotinib will be given at a dose of 150 mg per day for 4 weeks before undergoing planned radical cystectomy. In addition, patients will continue on erlotinib daily at a dose of 150 mg per day (qd dosing) for up to 2 years after surgery (beginning within 12 weeks of surgery) or until evidence of disease recurrence or progression
Radical Cystectomy: Will occur 4 weeks prior to dosing with erlotinib
|
|---|---|
|
Gastrointestinal disorders
Abdominal pain or cramping
|
8.7%
2/23 • 5 years
|
|
Investigations
Alkaline phosphatase
|
17.4%
4/23 • 5 years
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
4.3%
1/23 • 5 years
|
|
Investigations
Amylase
|
4.3%
1/23 • 5 years
|
|
Metabolism and nutrition disorders
Anorexia
|
43.5%
10/23 • 5 years
|
|
Respiratory, thoracic and mediastinal disorders
Apnea
|
4.3%
1/23 • 5 years
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
4.3%
1/23 • 5 years
|
|
Metabolism and nutrition disorders
Bicarbonate
|
17.4%
4/23 • 5 years
|
|
Renal and urinary disorders
Bladder spasms
|
4.3%
1/23 • 5 years
|
|
Vascular disorders
Cardiovascular/Arrhythmia-Afib/tachycardia
|
4.3%
1/23 • 5 years
|
|
Investigations
Coagulation-Elevated international normalized ratio (INR)
|
4.3%
1/23 • 5 years
|
|
Gastrointestinal disorders
Constipation
|
17.4%
4/23 • 5 years
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
17.4%
4/23 • 5 years
|
|
Investigations
CPK (creatine phosphokinase)
|
4.3%
1/23 • 5 years
|
|
Investigations
Creatinine
|
26.1%
6/23 • 5 years
|
|
Skin and subcutaneous tissue disorders
Dermatology/Skin-Other (Reynaud's)
|
4.3%
1/23 • 5 years
|
|
Skin and subcutaneous tissue disorders
Dermatology/Skin-Other (onychomycosis -on fingers -bilaterally)
|
4.3%
1/23 • 5 years
|
|
Skin and subcutaneous tissue disorders
Dermatology/Skin-Other (Paronychia)
|
4.3%
1/23 • 5 years
|
|
Skin and subcutaneous tissue disorders
Dermatology/Skin-Other (Boils on abdomen)
|
4.3%
1/23 • 5 years
|
|
Skin and subcutaneous tissue disorders
Dermatology/Skin-Other (Cracked Lips)
|
4.3%
1/23 • 5 years
|
|
Gastrointestinal disorders
Diarrhea
|
30.4%
7/23 • 5 years
|
|
Nervous system disorders
Dizziness/lightheadedness
|
4.3%
1/23 • 5 years
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
13.0%
3/23 • 5 years
|
|
Renal and urinary disorders
Dysuria
|
8.7%
2/23 • 5 years
|
|
General disorders
Fatigue
|
34.8%
8/23 • 5 years
|
|
Gastrointestinal disorders
Gastrointestinal-Other (Gastroesophageal reflux disease)
|
4.3%
1/23 • 5 years
|
|
Investigations
GGT (Gamma-Glutamyl transpeptidase)
|
8.7%
2/23 • 5 years
|
|
Eye disorders
Glaucoma
|
4.3%
1/23 • 5 years
|
|
Skin and subcutaneous tissue disorders
Hand-foot skin reaction
|
4.3%
1/23 • 5 years
|
|
Renal and urinary disorders
Hematuria (in the absence of vaginal cleeding)
|
21.7%
5/23 • 5 years
|
|
Blood and lymphatic system disorders
Hemoglobin
|
56.5%
13/23 • 5 years
|
|
Vascular disorders
Hemorrhage-Other (Hemorrhoid)
|
4.3%
1/23 • 5 years
|
|
Metabolism and nutrition disorders
Hyperglycemia
|
13.0%
3/23 • 5 years
|
|
Metabolism and nutrition disorders
Hyperkalemia
|
13.0%
3/23 • 5 years
|
|
Metabolism and nutrition disorders
Hypernatremia
|
8.7%
2/23 • 5 years
|
|
Vascular disorders
Hypertension
|
4.3%
1/23 • 5 years
|
|
Metabolism and nutrition disorders
Hypoalbuminemia
|
21.7%
5/23 • 5 years
|
|
Metabolism and nutrition disorders
Hypocalcemia
|
30.4%
7/23 • 5 years
|
|
Metabolism and nutrition disorders
Hypoglycemia
|
4.3%
1/23 • 5 years
|
|
Metabolism and nutrition disorders
Hypokalemia
|
17.4%
4/23 • 5 years
|
|
Metabolism and nutrition disorders
Hypomagnesemia
|
34.8%
8/23 • 5 years
|
|
Metabolism and nutrition disorders
Hyponatremia
|
30.4%
7/23 • 5 years
|
|
Metabolism and nutrition disorders
Hypophosphatemia
|
4.3%
1/23 • 5 years
|
|
Renal and urinary disorders
Incontinence
|
4.3%
1/23 • 5 years
|
|
Infections and infestations
Infection with unknown ANC
|
4.3%
1/23 • 5 years
|
|
Infections and infestations
Infection without neutropenia
|
13.0%
3/23 • 5 years
|
|
Infections and infestations
Infection/Febrile Neutropenia-Other (Urinary tract infection - intermittent)
|
4.3%
1/23 • 5 years
|
|
Psychiatric disorders
Insomnia
|
4.3%
1/23 • 5 years
|
|
Investigations
Lipase
|
4.3%
1/23 • 5 years
|
|
Investigations
Lymphopenia
|
17.4%
4/23 • 5 years
|
|
Psychiatric disorders
Mood alteration - Anxiety
|
4.3%
1/23 • 5 years
|
|
Psychiatric disorders
Mood alteration - Anxiety, agitation
|
4.3%
1/23 • 5 years
|
|
Psychiatric disorders
Mood alteration- Depression
|
13.0%
3/23 • 5 years
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal-Other (Gout flare)
|
4.3%
1/23 • 5 years
|
|
Gastrointestinal disorders
Nausea
|
21.7%
5/23 • 5 years
|
|
Nervous system disorders
Neuropathy-sensory
|
4.3%
1/23 • 5 years
|
|
Gastrointestinal disorders
Pain - Abdomen NOS
|
4.3%
1/23 • 5 years
|
|
Musculoskeletal and connective tissue disorders
Pain - Back
|
8.7%
2/23 • 5 years
|
|
General disorders
Pain-Other (Cramping - Hands/Feet)
|
4.3%
1/23 • 5 years
|
|
General disorders
Pain-Other (Pain - rash induced)
|
4.3%
1/23 • 5 years
|
|
Investigations
Partial thromboplastin time (PTT)
|
4.3%
1/23 • 5 years
|
|
Investigations
Platelets
|
13.0%
3/23 • 5 years
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
4.3%
1/23 • 5 years
|
|
Skin and subcutaneous tissue disorders
Rash/desquamation
|
91.3%
21/23 • 5 years
|
|
Renal and urinary disorders
Renal/Genitourinary - Other (Dysuria)
|
4.3%
1/23 • 5 years
|
|
Renal and urinary disorders
Renal/Genitourinary-Other (Candida urinary tract infection (UTI))
|
4.3%
1/23 • 5 years
|
|
Investigations
SGOT (AST) (serum glutamic oxaloacetic transaminase)
|
13.0%
3/23 • 5 years
|
|
Investigations
SGPT (ALT) (serum glutamic pyruvic transaminase)
|
4.3%
1/23 • 5 years
|
|
Gastrointestinal disorders
Stomatitis/pharyngitis (oral/pharyngeal mucositis)
|
8.7%
2/23 • 5 years
|
|
Skin and subcutaneous tissue disorders
Sweating (diaphoresis)
|
4.3%
1/23 • 5 years
|
|
Nervous system disorders
Syncope
|
4.3%
1/23 • 5 years
|
|
Nervous system disorders
Taste disturbance (dysgeusia)
|
17.4%
4/23 • 5 years
|
|
Nervous system disorders
Tremor
|
4.3%
1/23 • 5 years
|
|
Renal and urinary disorders
Urinary frequency/urgency
|
52.2%
12/23 • 5 years
|
|
Cardiac disorders
Ventricular arrhythmia (PVCs/bigeminy/trigeminy/ventricular tachycardia)
|
4.3%
1/23 • 5 years
|
|
Gastrointestinal disorders
Vomiting
|
8.7%
2/23 • 5 years
|
Additional Information
Robin V. Johnson
UNC Lineberger Comprehensive Cancer Center
Phone: 919-966-1125
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place