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Bladder CarcinomaPhase 2NCT02169284

Erlotinib Hydrochloride in Treating Patients With Bladder Cancer Undergoing Surgery

A Phase 2 study testing Erlotinib Hydrochloride, Laboratory Biomarker Analysis and Pharmacological Study in people with Bladder Carcinoma and Recurrent Bladder Carcinoma, run by National Cancer Institute (NCI) at 6 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Erlotinib Hydrochloride, Laboratory Biomarker Analysis and Pharmacological Study
Type of treatment
Surgery or procedure
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
50 participants
Where
6 sitesUnited States
Study dates
1 Oct 2014to 30 Mar 2018
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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

Who cannot join

  • 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
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  • 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

Trial locations and contacts

6 sites in 1 country.

6 sites in 1 country

United States6 sites

  • Johns Hopkins University/Sidney Kimmel Cancer Center

    Baltimore, Maryland, 21287

  • Lahey Hospital and Medical Center

    Burlington, Massachusetts, 01805

  • University of Wisconsin Hospital and Clinics

    Madison, Wisconsin, 53792

  • Carolina Urologic Research Center

    Myrtle Beach, South Carolina, 29572

  • University of Rochester

    Rochester, New York, 14642

  • Urology San Antonio Research PA

    San Antonio, Texas, 78229

Other trials in United States

About this study

Official title: Phase II Clinical Chemoprevention Trial of Weekly Erlotinib Before Bladder Cancer Surgery

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.

Read the detailed description

PRIMARY OBJECTIVES:

  1. 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:

  1. 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.

  1. 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.

Being tested
Erlotinib Hydrochloride, Laboratory Biomarker Analysis, Pharmacological Study, Placebo, Quality-of-Life Assessment
Medical subject headings
Urinary Bladder Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Erlotinib HydrochlorideDrug

    Also called Cp-358,774, OSI-774, Tarceva

    Given PO

  • Laboratory Biomarker AnalysisOther

    Correlative studies

  • Pharmacological StudyOther

    Correlative studies

  • PlaceboOther

    Also called placebo therapy, PLCB, sham therapy

    Given PO

  • Quality-of-Life AssessmentOther

    Also called Quality of Life Assessment

    Ancillary studies

  • Therapeutic Conventional SurgeryProcedure or surgery

    Undergo TURBT or cystectomy

Study groups in NCT02169284
Study groupRoleWhat they receive
Group I (erlotinib hydrochloride)ExperimentalPatients receive erlotinib hydrochloride PO QD on days 1, 8, and 15. Patients then undergo TURBT or cystectomy on day 16.
Receives: Drug: Erlotinib Hydrochloride; Other: Laboratory Biomarker Analysis; Other: Pharmacological Study; Other: Quality-of-Life Assessment; Procedure: Therapeutic Conventional Surgery
Group II (placebo)Placebo comparatorPatients receive placebo PO QD on days 1, 8, and 15. Patients then undergo TURBT or cystectomy on day 16.
Receives: Other: Laboratory Biomarker Analysis; Other: Pharmacological Study; Other: Placebo; Other: Quality-of-Life Assessment; Procedure: Therapeutic Conventional Surgery

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: Up to 18 hours after last study drug dose (on day 28)

Secondary outcomes (9)

  1. 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.

    Measured: Up to 18 hours after last study drug dose (on day 28)

  2. Pharmacokinetic Parameters: Erlotinib in Blood

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

    Measured: Baseline, day 8, and day 16 (day of surgery)

  3. Pharmacokinetic Parameters: OSI-420 in Blood

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

    Measured: Baseline, day 8, and day 16 (day of surgery)

  4. 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.

    Measured: Baseline up to 18 hours after last study drug dose (on day 28)

  5. 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.

    Measured: At time of surgery (approximately day 16)

  6. 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.

    Measured: At time of surgery (approximately day 16)

  7. 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.

    Measured: At time of surgery (approximately day 16)

  8. 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.

    Measured: At time of surgery (approximately day 16)

  9. 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.

    Measured: At time of surgery (approximately day 16)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted23 Jun 2014 (estimated)
  2. Study start1 Oct 2014
  3. Primary completion30 Mar 2018
  4. Study completion30 Mar 2018

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
50 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02169284
Sponsor's protocol ID
NCI-2014-01320
Other IDs
NCI-2014-01320, HHSN261201200033I, N01-CN-2012-00033, CO12336, UWI2013-01-02, N01CN00033, P30CA014520
Status last verified
Jun 2020
First submitted
19 Jun 2014
Last updated
7 Jul 2020
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • Downs TM, Bailey HH, Lozar T, Schmitz NS, Green H, Scarlett CO, Havighurst TC, Twaroski K, DeShong K, Wollmer B, Bivalacqua TJ, Saltzstein DR, Shore N, Kim K, Huang W, Ricke WA, Barroilhet L, House M, Parnes HL, Messing E. Phase II Clinical Chemoprevention Trial of Weekly Erlotinib before Bladder Cancer Surgery. Cancer Prev Res (Phila). 2025 Jan 6;18(1):31-39. doi: 10.1158/1940-6207.CAPR-24-0194.

    PubMed 39187984

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Erlotinib Hydrochloride, Laboratory Biomarker Analysis and Pharmacological Study in people with Bladder Carcinoma and Recurrent Bladder Carcinoma, run by National Cancer Institute (NCI) at 6 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 23 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 7 Jul 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 6 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 7 Jul 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

EGFR Phosphorylation in Normal Appearing Bladder Epithelium Adjacent to Tumor (time frame: Up to 18 hours after last study drug dose (on day 28)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02169284, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Jul 2020.

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