Docetaxel and Lapatinib in Metastatic Transitional Cell Carcinoma in Bladder

This study has been terminated.
(Trial not progressing toward scientific goals)
Sponsor:
Collaborators:
GlaxoSmithKline
Information provided by (Responsible Party):
University of Southern California
ClinicalTrials.gov Identifier:
NCT01382706
First received: June 23, 2011
Last updated: February 5, 2014
Last verified: February 2014
  Purpose

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.


Condition Intervention Phase
Recurrent Bladder Cancer
Stage III Bladder Cancer
Stage IV Bladder Cancer
Transitional Cell Carcinoma of the Bladder
Drug: docetaxel
Drug: lapatinib ditosylate
Other: immunohistochemistry staining method
Genetic: fluorescence in situ hybridization
Other: laboratory biomarker analysis
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Single Arm Phase II Study of Docetaxel and Lapatinib in Metastatic Transitional Cell Carcinoma in Bladder as Second Line Treatment

Resource links provided by NLM:


Further study details as provided by University of Southern California:

Primary Outcome Measures:
  • Progression-free survival rate [ Time Frame: At 12 weeks ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Objective response rates [ Time Frame: After 6 and 12 weeks and then every 9 weeks ] [ Designated as safety issue: No ]
  • Overall survival [ Time Frame: Every 6 months for up to 2 years ] [ Designated as safety issue: No ]
  • To study tolerability and safety by assessing the incidence and nature of Grade 3, 4 and serious adverse events [ Time Frame: Weeks 1, 4, 7, 10, 13, 16, 19, 22 and then every 6 months for up to 2 years ] [ Designated as safety issue: Yes ]

Enrollment: 15
Study Start Date: June 2011
Estimated Study Completion Date: July 2015
Estimated Primary Completion Date: July 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment
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
Given IV
Other Names:
  • RP 56976
  • Taxotere
  • TXT
Drug: lapatinib ditosylate
Given PO
Other Names:
  • GSK572016
  • GW-572016
  • GW2016
  • Lapatinib
  • Tykerb
Other: immunohistochemistry staining method
Correlative studies
Other Name: immunohistochemistry
Genetic: fluorescence in situ hybridization
Correlative studies
Other Name: fluorescence in situ hybridization (FISH)
Other: laboratory biomarker analysis
Correlative studies

Detailed Description:

PRIMARY OBJECTIVES:

I. 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:

I. 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:

I. 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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
  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01382706

Locations
United States, California
USC/Norris Comprehensive Cancer Center
Los Angeles, California, United States, 90033
Sponsors and Collaborators
University of Southern California
GlaxoSmithKline
Investigators
Principal Investigator: David Quinn, M.D. University of Southern California
  More Information

No publications provided

Responsible Party: University of Southern California
ClinicalTrials.gov Identifier: NCT01382706     History of Changes
Other Study ID Numbers: 4B-10-4, NCI-2011-01108
Study First Received: June 23, 2011
Last Updated: February 5, 2014
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Urinary Bladder Neoplasms
Carcinoma
Carcinoma, Transitional Cell
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Urinary Bladder Diseases
Urologic Diseases
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Docetaxel
Lapatinib
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Protein Kinase Inhibitors
Enzyme Inhibitors

ClinicalTrials.gov processed this record on August 20, 2014