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Bladder CarcinomaEarly Phase 1LAPAINBLADNCT01245660

A Phase 0 of Neoadjuvant Lapatinib in Infiltrative Bladder Carcinoma Before Cystectomy

A Early Phase 1 study testing LAPATINIB in people with Bladder Carcinoma and Infiltrative Bladder Carcinoma, run by University Hospital, Bordeaux at 1 site in France.

Terminated

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

Official record
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Trial summary

Modification of the EGF signalling pathway and / or HER 2, by Lapatinib in bladder cancer. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
LAPATINIB
Could I receive a placebo?
No, everyone receives an active treatment
How many people
3 participants
Where
1 siteFrance
Study dates
Jan 2011to Oct 2011
Phase
Early Phase 1
Are there results?
None posted in the registry

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

  • Patients must sign and date IRB/EC-approved informed consent,
  • Age ≥ 18
  • Patients must have a life expectancy of at least 6 months,
  • Patients must have a Karnofsky performance status ≥ 80%,
  • Clinical stage T2NxM0 to T4aNxM0 bladder cancer
  • Muscle-invasive transitional cell carcinoma by histology (focal squamous and/or adenocarcinoma differentiation defined as ≤ 10% of tumor volume allowed, sarcomatoid and small-cell components not allowed)
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  • Considered to have a macroscopic residue in the bladder to allow comparison of tissue samples at cystectomy to initial biopsies
  • Candidates for radical cystectomy
  • Patient with normal cardiac function, LVEF ≥ 50% measured by echocardiography or MUGA scan
  • Able to swallow and retain oral medication
  • A female is eligible to enter and participate in this study if she is of : Non-child-bearing potential (i.e., a woman with functioning ovaries who have a current documented tubal ligation or hysterectomy or a woman who is menopausal), or Child-bearing potential (i.e. a woman with functioning ovaries and no documented impairment of oviductal or uterine function that would cause sterility. This category includes women with oligomenorrhoea (even severe), women who are perimenopausal and young women who have begun to menstruate), who have a negative serum pregnancy test at screening, and agree to one of the following consistent and correct use of one acceptable methods of birth control : Any intrauterine device (IUD) with a documented failure rate of less than 1% per year, or combined oral contraception
  • care must be taken to avoid pregnancy in partners of male patients.
  • Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures.
  • Affiliated or profit patient of a social security system

Who cannot join

  • Prior pelvic radiation or neoadjuvant chemotherapy.
  • Pregnancy or breastfeeding.
  • Other severe acute or chronic medical or psychiatric condition that would impart, in the judgment of the investigator, excess risk associated with study participation or study drug administration, or which, in the judgment of the investigator, would make the patient inappropriate for entry into this study.
  • Patients with significantly reduced LVEF or LVEF < 50%.
  • Patient with any of the following liver abnormal laboratory test :
  • Serum bilirubin > 1,5 x upper limit of normal (ULN) (in case of Gilbert syndrome, a higher serum total bilirubin (< 2 ULN) is allowed
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  • Alanine amino transferase (ALAT) or aspartate amino transferase (ASAT) > 2,5 ULN
  • Platelets <100 x 109/L, hemoglobin < 9 g/dl, absolute neutrophil count (ANC) <1.5 x 109/L
  • Have current active hepatic or biliary disease (with exception of patients with Gilbert's syndrome, asymptomatic gallstones, liver metastases or stable chronic liver disease per investigator assessment)
  • Serum creatinine > 1.5 x ULN.
  • Previous therapy targeting EGFR or HER-2.
  • Predominantly non transitional cell histology.
  • Diagnosis of any second malignancy within the last 3 years, except basal cell carcinoma, squamous cell skin cancer, or in situ carcinoma of the cervix uteri that has been adequately treated with no evidence of recurrent disease for 12 months.
  • Malabsorption syndrome, disease significantly affecting gastrointestinal function, or major resection of the stomach or bowel, that could affect absorption of lapatinib.
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to lapatinib
  • Uncontrolled inter-current illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, that would limit compliance with study requirements.
  • History of uncontrolled or symptomatic angina
  • History of arrhythmias requiring medications, or clinically significant, with the exception of asymptomatic atrial fibrillation requiring anticoagulation
  • Myocardial infarction < 6 months from study entry
  • Uncontrolled or symptomatic congestive heart failure
  • Ejection fraction below the institutional normal limit
  • Any other cardiac condition, which in the opinion of the treating physician, would make this protocol unreasonably hazardous for the patient
  • Use of an investigational agent within 30 days or 5 half-lives, whichever is the longer, preceding the first dose of investigational product.
  • Concurrent treatment with an investigational agent
  • Concurrent treatment with cytotoxic chemotherapy, immunotherapy, biologic therapy, hormonal therapy or curative radiotherapy for locally advanced or metastatic TCC of the urothelial tract.
  • Concomitant requirement for medication classified as CYP3A4 inducers or inhibitors.
  • Patient under safeguard of justice

Trial locations and contacts

1 site in 1 country.

France1 site

  • CHU Bordeaux - Hôpital Saint André - Department of Medical Oncology

    Bordeaux, 33075

Other trials in France

About this study

Official title: Pilot Study of Lapatinib (Tyverb®) in Neoadjuvant Treatment for Patients With Locally Bladder Carcinoma Before Cystectomy

Modification of the EGF signalling pathway and / or HER 2, by Lapatinib in bladder cancer.

Read the detailed description

Patients with invasive bladder tumor , candidates for radical cystectomy. Patients will receive Lapatinib during 3 weeks +/- 5 days, before cystectomy. A comparison of tissue from the original biopsy and cystectomy after Lapatinib will allow this to occur.

TREATMENT AND STRATEGY Lapatinib in bladder carcinoma -Overall there are arguments for considering that egf pathway is involved in bladder carcinoma and so far that drugs inhibiting EGF pathway could have an impact for therapeutical endpoints.

Nevertheless it is unclear that from previous studies that adding egf inhibiting drug to chemotherapy is clinically relevant, essentially by difficulties to measure a beneficial endpoint while downstream EGF pathways have been modified by these drugs, as shown with lapatinib (see 2.1.5).

Furthermore, there is no argument for initial selection of patients based on the initial egfr and/or her 2 tumor profile, asking for more intense knowledge.

LAPATINIB TREATMENT Patients will receive lapatinib therapy at a daily standard dose of 1500 mg.

LAPATINIB TREATMENT DURATION Patients will then receive 3 weeks of lapatinib therapy + possible 5 days. As the study is a non direct benefit study, the exposition to the drug is proposed during the standard window of 3 to 4 weeks to organize a radical cystectomy in patients with muscle invasive bladder carcinoma. In this study patients, the standard procedure is not delayed for the purpose of the study.

The duration of exposition to lapatinib as to be long enough to have a continuous impact of biological events to induce indeed inhibition of EGF pathway but also to impact on more complex or more distal events as apoptosis and so to be able to measure it. This justifies a 3 weeks of treatment + possible up to 5 days more due to surgical organization procedures.

Surgery will take place on the last day of treatment, which is recommended due to the half-life of lapatinib. Nevertheless for surgical purpose, the drug could be not given on the day of surgery.

Being tested
LAPATINIB
Keywords
Phase 0, Bladder carcinoma, egf pathway, infiltrative bladder carcinoma, cystectomy, LAPATINIB
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.

  • LAPATINIBDrug

    Lapatinib, 1250 mg per day, per os, during 3 weeks +/- 5 days.

Study groups in NCT01245660
Study groupRoleWhat they receive
PatientExperimentalNot described
Receives: Drug: LAPATINIB

What is being measured

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

  1. Effect on egf pathway at a molecular level of 3 weeks treatment by lapatinib.

    The primary objective of the study is to evaluate the effect at a molecular level, of 3 weeks of neoadjuvant lapatinib, in locally advanced muscle-invasive transitional cell carcinoma of the bladder. A comparison of tissue from the original biopsy and cystectomy after lapatinib will allow this to occur. This effect will be evaluated by studying proliferation and apoptotic markers as well as the phosphorylation of proteins which are components of the egf signalling pathway.

    Measured: At surgery (day 21-27)

Secondary outcomes (2)

  1. Lapatinib biological response on key molecules of the egf pathway (EGFR, ERBB2, AKT ERK as well as their phosphorylation status.)

    Because the availability of large scale data, the correlation between lapatinib biological response and the molecular alteration of other molecules beside those involved in the egf pathway will be explored. i.e. key molecules of the pathway will also be studied at the protein level (EGFR, ERBB2, AKT ERK) as well as their phosphorylation status.

    Measured: At screening (day -10 before inclusion) , surgery (day 21-27) and Follow up visit surgery (day 42-62)

  2. Histological response

    To evaluate the histological response to lapatinib at the time of surgery

    Measured: At surgery (day 21-27)

Timeline

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

  1. First posted22 Nov 2010 (estimated)
  2. Study startJan 2011
  3. Primary completionOct 2011
  4. Study completionOct 2011

Why it stopped: The rythm of enrollment was not compatible with the objective of recruitement in the research.

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
Early Phase 1
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
3 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01245660
Sponsor's protocol ID
CHUBX 2009/04
Acronym
LAPAINBLAD
Status last verified
Jan 2013
First submitted
18 Nov 2010
Last updated
11 Jan 2013
Results posted
No
Data monitoring committee
Yes

Publications

  • Rodel C, Weiss C, Sauer R. Trimodality treatment and selective organ preservation for bladder cancer. J Clin Oncol. 2006 Dec 10;24(35):5536-44. doi: 10.1200/JCO.2006.07.6729.

    PubMed 17158539

  • Jimenez RE, Hussain M, Bianco FJ Jr, Vaishampayan U, Tabazcka P, Sakr WA, Pontes JE, Wood DP Jr, Grignon DJ. Her-2/neu overexpression in muscle-invasive urothelial carcinoma of the bladder: prognostic significance and comparative analysis in primary and metastatic tumors. Clin Cancer Res. 2001 Aug;7(8):2440-7.

    PubMed 11489824

  • Advanced Bladder Cancer (ABC) Meta-analysis Collaboration. Neoadjuvant chemotherapy in invasive bladder cancer: update of a systematic review and meta-analysis of individual patient data advanced bladder cancer (ABC) meta-analysis collaboration. Eur Urol. 2005 Aug;48(2):202-5; discussion 205-6. doi: 10.1016/j.eururo.2005.04.006. Epub 2005 Apr 21.

    PubMed 15939524

Questions about this trial

What is this clinical trial studying?

A Early Phase 1 study testing LAPATINIB in people with Bladder Carcinoma and Infiltrative Bladder Carcinoma, run by University Hospital, Bordeaux at 1 site in France.

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 14 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 11 Jan 2013. 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 France. 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?

Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.

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

Are results available for this study?

The study was stopped early (reason given: The rythm of enrollment was not compatible with the objective of recruitement in the research.). Results are not available in the source record.

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?

Effect on egf pathway at a molecular level of 3 weeks treatment by lapatinib. (time frame: At surgery (day 21-27)). 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 NCT01245660, which also lists 3 linked publications.

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 11 Jan 2013.

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