Docetaxel and Lapatinib in Metastatic Transitional Cell Carcinoma in Bladder

NCT01382706 | Terminated Phase 2 Results DMC FDA Drug

• 2 other identifiers: 4B-10-4NCI-2011-01108
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Recurrent Bladder Cancer; Stage III Bladder Cancer; Stage IV Bladder Cancer; Transitional Cell Carcinoma of the Bladder

Outcome Measures

Primary Outcomes (1)

• 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.

  At 12 weeks

Secondary Outcomes (1)

• Incidence Grade 3 or Higher Serious Adverse Events (SAE)

  Weeks 1, 4, 7, 10, 13, 16, 19, 22 and then every 6 months for up to 2 years

Study Arms (1)

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.

Drug: docetaxel; Drug: lapatinib ditosylate; Other: immunohistochemistry staining method; Genetic: fluorescence in situ hybridization; Other: laboratory biomarker analysis

Interventions

docetaxel DRUG

Given IV

Also known as: RP 56976, Taxotere, TXT

Treatment

lapatinib ditosylate DRUG

Given PO

Also known as: GSK572016, GW-572016, GW2016, Lapatinib, Tykerb

Treatment

immunohistochemistry staining method OTHER

Correlative studies

Also known as: immunohistochemistry

Treatment

fluorescence in situ hybridization GENETIC

Correlative studies

Also known as: fluorescence in situ hybridization (FISH)

Treatment

laboratory biomarker analysis OTHER

Correlative studies

Treatment

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)
• 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

You may not qualify if:

• 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.
• 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
• 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

Sponsors & Collaborators

• University of Southern California: lead
• National Cancer Institute (NCI): collaborator
• GlaxoSmithKline: collaborator

Study Sites (1)

USC/Norris Comprehensive Cancer Center

Los Angeles, California, 90033, United States

Location

MeSH Terms

Conditions

Urinary Bladder Neoplasms

Interventions

Docetaxel; Lapatinib; N-(3-chloro-4-((3-fluorobenzyl)oxy)phenyl-6-(5-((methylsulfonyl)ethyl)aminomethyl)-2-furyl)-4-quinazolinamine; Immunohistochemistry; In Situ Hybridization, Fluorescence

Condition Hierarchy (Ancestors)

Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Histocytochemistry; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Histological Techniques; Investigative Techniques; Immunologic Techniques; In Situ Hybridization; Staining and Labeling; Histocytological Preparation Techniques; Cytogenetic Analysis; Genetic Techniques; Nucleic Acid Hybridization

Results Point of Contact

• Title: Tali Homsey
• Organization: USC/Norris Comprehensive Cancer Center

tali.homsey@med.usc.edu

(323) 865-0451

Study Officials

• David Quinn, M.D.

  University of Southern California

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 23, 2011
• First Posted: June 27, 2011
• Study Start: June 13, 2011
• Primary Completion: July 15, 2013
• Study Completion: December 15, 2017
• Last Updated: October 9, 2025
• Results First Posted: October 9, 2025

Record last verified: 2025-09

Locations

US (1)