Recurrent Bladder CancerPhase 2NCT01382706
Docetaxel and Lapatinib in Metastatic Transitional Cell Carcinoma in Bladder
A Phase 2 study testing docetaxel, lapatinib ditosylate and immunohistochemistry staining method in people with Recurrent Bladder Cancer and Stage III Bladder Cancer, run by University of Southern California at 1 site in United States.
Trial summary
This phase II trial studies how well giving docetaxel and lapatinib ditosylate together as second-line therapy works in treating patients with stage IV bladder cancer that cannot be removed by surgery. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Recurrent Bladder Cancer, Stage III Bladder Cancer, Stage IV Bladder Cancer
- What is being tested?
- docetaxel, lapatinib ditosylate and immunohistochemistry staining method
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 15 participants
- Where
- 1 siteUnited States
- Study dates
- 13 Jun 2011to 15 Dec 2017
- 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
- Histologically or cytologically confirmed transitional cell carcinoma of the urothelium (also called urothelial cancer); mixed histologies are allowed as long as the predominant histology is TCC; in addition, tumor tissue must be available for evaluation for EGFR and HER2/neu status
- Locally recurrent or advanced, non-resectable or stage IV transitional cell carcinoma
- Must have had prior platinum salt-based chemotherapy for TCC; other prior systemic chemotherapeutic or investigational treatment regimens for TCC are allowed; patient may have had up to three lines of chemotherapy for advanced disease; may have had paclitaxel provided their cancer did not progress while on it, and it was part of an adjuvant or neoadjuvant regimen; prior targeted or biological therapy is permitted except for drugs targeting EGFR and/or HER2; specifically, subjects must meet one or more of the following criteria: (a). Progression after treatment with a regimen that includes a platinum salt (e.g. carboplatin or cisplatin) for Stage IV or recurrent disease OR (b). Disease recurrence within two years (from the date of last dose of chemotherapy or surgery until day the informed consent is signed) of neoadjuvant or adjuvant treatment with a regimen that includes a platinum salt
- Measurable or evaluable disease, as defined by Response Evaluation Criteria In Solid Tumors (RECIST) 1.1; if all sites of measurable or evaluable disease have been irradiated, one site must have demonstrated growth after irradiation
- A left ventricular ejection fraction (LVEF) within normal range as measured by echocardiogram or multi-gated acquisition (MUGA) scan
- Adequate contraceptive method for subjects with reproductive potential (females with reproductive potential must have a negative serum pregnancy test within 7 days of study entry)
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- Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
- A signed written informed consent
- Due to the experimental nature of lapatinib, female subjects must be one year postmenopausal, surgically sterile, or using an acceptable method of contraception (oral contraceptives, barrier methods, approved contraceptive implant, long-term injectable contraception, intrauterine device or tubal ligation); male subjects must be surgically sterile or using an acceptable method of contraception during their participation in this study
Who cannot join
- History of treatment of TCC (in any setting - neoadjuvant, adjuvant or for metastatic disease) with docetaxel
- History of treatment with an EGFR or HER2 targeted agent
- Serum bilirubin more than 1.5 x the upper limit of normal (ULN) except in patients with diagnosis of Gilbert's disease
- Creatinine clearance less than 20 mL/minute (calculated by the Cockcroft-Gault formula)
- Potassium, less than institutional normal level despite supplementation; serum calcium (ionized or adjusted for albumin,) or magnesium below lower limits of normal despite supplementation
- Baseline liver function test including AST or ALT greater than 2.5 x institutional upper limits of normal.
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- Absolute neutrophil count (ANC) less than 1500/uL
- Platelets less than 100/uL
- Evidence of severe or uncontrolled systemic disease or any concurrent condition which in the Investigator's opinion makes it undesirable for the subject to participate in the trial or which would jeopardize compliance with the protocol
- An abnormal left ventricular ejection fraction LVEF as measured by echocardiogram or MUGA scan or other suitable technique
- Clinically significant cardiac event such as myocardial infarction; New York Heart Association (NYHA) classification of heart disease more than class 2 within 3 months before entry; or presence of cardiac disease that, in the opinion of the Investigator, increases the risk of ventricular arrhythmia
- History of arrhythmia (multifocal premature ventricular contractions [PVCs], bigeminy, trigeminy, ventricular tachycardia, or uncontrolled atrial fibrillation) which is symptomatic or requires treatment (Common Terminology Criteria for Adverse Events [CTCAE] grade 3) or asymptomatic sustained ventricular tachycardia; atrial fibrillation controlled on medication is not exclusion nor are infrequent or unifocal ectopic beats
- Current QTc prolongation as a result of medication will require discontinuation of that medication; the patient can be reassessed after discontinuation, provided this is medically appropriate, after 2 weeks or five half-lives of the drug have passed whichever is longer
- Congenital long QT syndrome or 1st degree relative with unexplained sudden death under 40 years of age
- Presence of left bundle branch blocks (LBBB)
- QTc with Bazett's correction that is unmeasurable, or exceeds 480 msec on screening electrocardiogram (ECG); if a subject has QTc > 480 msec on screening ECG, the screen ECG may be repeated twice (at least 24 hours apart); the average QTc from the three screening ECGs must be < 480 msec in order for the subject to be eligible for the study
- Any concomitant medication that may cause QTc prolongation, induce Torsades de Pointes or induce cytochrome P450 3A4 (CYP3A4) function
- Hypertension not controlled by medical therapy
- Currently active diarrhea
- Women who are currently pregnant or breast feeding
- Receipt of any investigational agent, chemotherapy or radiation therapy within 21 days prior to Study Day 1
- Any unresolved non-hematologic toxicity greater than CTCAE grade 1 from previous anti-cancer therapy (other than alopecia)
- Major surgery within 4 weeks or incompletely healed surgical incision before starting study therapy
- Grade 2 or greater peripheral neuropathy
- Previous or current malignancies within the last 3 years, with the exception of in situ carcinoma of the cervix, adequately treated carcinoma of the skin, small renal masses, and adequately treated localized prostate cancer; other cancers that are highly likely to be cured (cure rate of 75% or greater) may be included at the discretion of the Principal Investigator
- History of severe hypersensitivity reaction to drugs formulated with polysorbate 80
- Patients with brain metastasis can only be included if they were treated more than 4 weeks prior to enrollment; subjects with treated brain metastases must have a post treatment brain magnetic resonance imaging (MRI) showing no further progression of prior lesions AND no new metastatic lesions; subjects will be ineligible if they have any ongoing symptoms from brain metastases or if there continues to be radiographic evidence of cerebral edema
Trial locations and contacts
1 site in 1 country.
United States1 site
USC/Norris Comprehensive Cancer Center
Los Angeles, California, 90033
About this study
Official title: Single Arm Phase II Study of Docetaxel and Lapatinib in Metastatic Transitional Cell Carcinoma in Bladder as Second Line Treatment
This phase II trial studies how well giving docetaxel and lapatinib ditosylate together as second-line therapy works in treating patients with stage IV bladder cancer that cannot be removed by surgery. Drugs used in chemotherapy, such as docetaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Lapatinib ditosylate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving docetaxel and lapatinib ditosylate together may kill more tumor cells.
Read the detailed description
PRIMARY OBJECTIVES:
- To assess the efficacy of 1250 mg of lapatinib (lapatinib ditosylate) given in combination with docetaxel in prolonging progression-free survival of subjects with metastatic, previously treated transitional cell carcinoma (TCC) relative to historical controls.
SECONDARY OBJECTIVES:
- To assess the efficacy of 1250 mg of Lapatinib given in combination with docetaxel in the objective response rates and overall survival.
II. To study the tolerability and safety of 1250 mg of lapatinib given in combination with docetaxel by assessing the incidence and nature of Grade 3, 4 and serious adverse events (AEs).
TERTIARY OBJECTIVES:
- To assess the expression status of epidermal growth factor receptor (EGFR) or human epidermal growth factor receptor 2 (HER-2) in tumor tissue and/or circulating tumor cells (CTCs) as potential predictors of response to therapy.
II. To evaluate the number of CTC's present in 7.5mLs of peripheral blood as a predictor for disease progression and response of treatment in bladder cancer in the setting of combination therapy of lapatinib and docetaxel.
III. To evaluate the effect of lapatinib in human at molecular level by targeting the phosphorylation activity of the AKT/extracellular-regulated kinase (ERK) on pathway prior and during the treatment with lapatinib.
OUTLINE: Patients receive docetaxel intravenously (IV) over 1 hour on day 1 and lapatinib ditosylate orally (PO) once daily (QD) on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 6 months for up to 2 years.
- Conditions
- Recurrent Bladder Cancer, Stage III Bladder Cancer, Stage IV Bladder Cancer, Transitional Cell Carcinoma of the Bladder
- Being tested
- docetaxel, lapatinib ditosylate, immunohistochemistry staining method, fluorescence in situ hybridization, laboratory biomarker analysis
- 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.
docetaxelDrug
Also called RP 56976, Taxotere, TXT
Given IV
lapatinib ditosylateDrug
Also called GSK572016, GW-572016, GW2016, Lapatinib
Given PO
immunohistochemistry staining methodOther
Also called immunohistochemistry
Correlative studies
fluorescence in situ hybridizationGenetic
Also called fluorescence in situ hybridization (FISH)
Correlative studies
laboratory biomarker analysisOther
Correlative studies
| Study group | Role | What they receive |
|---|---|---|
| Treatment | Experimental | Patients receive docetaxel IV over 1 hour on day 1 and lapatinib ditosylate PO QD on days 1-21. Courses repeat every 21 days until disease progression or unacceptable toxicity. Receives: Drug: docetaxel; Drug: lapatinib ditosylate; Other: immunohistochemistry staining method; Genetic: fluorescence in situ hybridization; Other: laboratory biomarker analysis |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression-free Survival Rate
Defined as the time period from the start of treatment and documented progression or death without documentation of progression. Summarized with Kaplan-Meier curves. The median will be estimated using a non-parametric method.
Measured: At 12 weeks
Secondary outcomes (1)
Incidence Grade 3 or Higher Serious Adverse Events (SAE)
Serious Adverse Events will be assessed according to CTCAE version 4.0
Measured: Weeks 1, 4, 7, 10, 13, 16, 19, 22 and then every 6 months for up to 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jun 2011 (estimated)
- Study start13 Jun 2011
- Primary completion15 Jul 2013
- Study completion15 Dec 2017
Why it stopped: Trial not progressing toward scientific goals
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Recurrent Bladder CancerStudies of the same condition, open and under way.
- More trials run by University of Southern CaliforniaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 15 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Southern California
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI), GlaxoSmithKline
- Responsible party
- Sponsor
- Investigators
- David Quinn, M.D., Principal investigator, University of Southern California
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01382706
- Sponsor's protocol ID
- 4B-10-4
- Other IDs
- NCI-2011-01108
- Status last verified
- Sep 2025
- First submitted
- 23 Jun 2011
- Last updated
- 9 Oct 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 9 Oct 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Single Arm Phase II Study of Docetaxel and Lapatinib in Metastatic Transitional Cell Carcinoma in Bladder as Second Line Treatment
- ClinicalTrials.gov ID
- NCT01382706
- Acronym / sponsor ID
- 4B-10-4
- Conditions
- Recurrent Bladder Cancer, Stage III Bladder Cancer, Stage IV Bladder Cancer, Transitional Cell Carcinoma of the Bladder
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Trial not progressing toward scientific goals
- Enrolment
- 15 participants (actual)
- Lead sponsor
- University of Southern CaliforniaUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI), GlaxoSmithKline
- Study start
- 13 Jun 2011 (actual)
- Primary completion
- 15 Jul 2013 (actual)
- Study completion
- 15 Dec 2017 (actual)
- First posted
- 27 Jun 2011 (estimated)
- Results
- Posted 9 Oct 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This phase II trial studies how well giving docetaxel and lapatinib ditosylate together as second-line therapy works in treating patients with stage IV bladder cancer that cannot be removed by surgery. Drugs used in chemotherapy, such as docetaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Lapatinib ditosylate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving docetaxel and lapatinib ditosylate together may kill more tumor cells.
Detailed description
PRIMARY OBJECTIVES:
- To assess the efficacy of 1250 mg of lapatinib (lapatinib ditosylate) given in combination with docetaxel in prolonging progression-free survival of subjects with metastatic, previously treated transitional cell carcinoma (TCC) relative to historical controls.
SECONDARY OBJECTIVES:
- To assess the efficacy of 1250 mg of Lapatinib given in combination with docetaxel in the objective response rates and overall survival.
II. To study the tolerability and safety of 1250 mg of lapatinib given in combination with docetaxel by assessing the incidence and nature of Grade 3, 4 and serious adverse events (AEs).
TERTIARY OBJECTIVES:
- To assess the expression status of epidermal growth factor receptor (EGFR) or human epidermal growth factor receptor 2 (HER-2) in tumor tissue and/or circulating tumor cells (CTCs) as potential predictors of response to therapy.
II. To evaluate the number of CTC's present in 7.5mLs of peripheral blood as a predictor for disease progression and response of treatment in bladder cancer in the setting of combination therapy of lapatinib and docetaxel.
III. To evaluate the effect of lapatinib in human at molecular level by targeting the phosphorylation activity of the AKT/extracellular-regulated kinase (ERK) on pathway prior and during the treatment with lapatinib.
OUTLINE: Patients receive docetaxel intravenously (IV) over 1 hour on day 1 and lapatinib ditosylate orally (PO) once daily (QD) on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 6 months for up to 2 years.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment | Experimental | Drug: docetaxel, Drug: lapatinib ditosylate, Other: immunohistochemistry staining method, Genetic: fluorescence in situ hybridization, Other: laboratory biomarker analysisPatients receive docetaxel IV over 1 hour on day 1 and lapatinib ditosylate PO QD on days 1-21. Courses repeat every 21 days until disease progression or unacceptable toxicity. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Histologically or cytologically confirmed transitional cell carcinoma of the urothelium (also called urothelial cancer); mixed histologies are allowed as long as the predominant histology is TCC; in addition, tumor tissue must be available for evaluation for EGFR and HER2/neu status
- Locally recurrent or advanced, non-resectable or stage IV transitional cell carcinoma
- Must have had prior platinum salt-based chemotherapy for TCC; other prior systemic chemotherapeutic or investigational treatment regimens for TCC are allowed; patient may have had up to three lines of chemotherapy for advanced disease; may have had paclitaxel provided their cancer did not progress while on it, and it was part of an adjuvant or neoadjuvant regimen; prior targeted or biological therapy is permitted except for drugs targeting EGFR and/or HER2; specifically, subjects must meet one or more of the following criteria: (a). Progression after treatment with a regimen that includes a platinum salt (e.g. carboplatin or cisplatin) for Stage IV or recurrent disease OR (b). Disease recurrence within two years (from the date of last dose of chemotherapy or surgery until day the informed consent is signed) of neoadjuvant or adjuvant treatment with a regimen that includes a platinum salt
- Measurable or evaluable disease, as defined by Response Evaluation Criteria In Solid Tumors (RECIST) 1.1; if all sites of measurable or evaluable disease have been irradiated, one site must have demonstrated growth after irradiation
- A left ventricular ejection fraction (LVEF) within normal range as measured by echocardiogram or multi-gated acquisition (MUGA) scan
Key exclusion criteria (27 listed)
- History of treatment of TCC (in any setting - neoadjuvant, adjuvant or for metastatic disease) with docetaxel
- History of treatment with an EGFR or HER2 targeted agent
- Serum bilirubin more than 1.5 x the upper limit of normal (ULN) except in patients with diagnosis of Gilbert's disease
- Creatinine clearance less than 20 mL/minute (calculated by the Cockcroft-Gault formula)
- Potassium, less than institutional normal level despite supplementation; serum calcium (ionized or adjusted for albumin,) or magnesium below lower limits of normal despite supplementation
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| docetaxelAlso: RP 56976, Taxotere, TXTGiven IV | Drug | Treatment |
| lapatinib ditosylateAlso: GSK572016, GW-572016, GW2016, LapatinibGiven PO | Drug | Treatment |
| immunohistochemistry staining methodAlso: immunohistochemistryCorrelative studies | Other | Treatment |
| fluorescence in situ hybridizationAlso: fluorescence in situ hybridization (FISH)Correlative studies | Genetic | Treatment |
| laboratory biomarker analysisCorrelative studies | Other | Treatment |
Primary outcome
Progression-free Survival Rate
Time frame: At 12 weeks
Defined as the time period from the start of treatment and documented progression or death without documentation of progression. Summarized with Kaplan-Meier curves. The median will be estimated using a non-parametric method.
1 secondary outcome
Incidence Grade 3 or Higher Serious Adverse Events (SAE)
Time frame: Weeks 1, 4, 7, 10, 13, 16, 19, 22 and then every 6 months for up to 2 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Oct 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
David Quinn, M.D. principal investigator
University of Southern California
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing docetaxel, lapatinib ditosylate and immunohistochemistry staining method in people with Recurrent Bladder Cancer and Stage III Bladder Cancer, run by University of Southern California at 1 site 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 9 inclusion and 27 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 9 Oct 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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. 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 9 Oct 2025). 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?
Progression-free Survival Rate (time frame: At 12 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 9 Oct 2025.