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

NCT01245660 | Terminated Early Phase 1 DMC

• 1 other identifier: CHUBX 2009/04
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Bladder Carcinoma; Infiltrative Bladder Carcinoma; Cystectomy

Keywords

Phase 0; Bladder carcinoma; egf pathway; infiltrative bladder carcinoma; cystectomy; LAPATINIB

Outcome Measures

Primary Outcomes (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.

  At surgery (day 21-27)

Secondary Outcomes (2)

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

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

• Histological response

  At surgery (day 21-27)

Study Arms (1)

Patient

EXPERIMENTAL

Drug: LAPATINIB

Interventions

LAPATINIB DRUG

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

Patient

Eligibility Criteria

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

You may qualify if:

• 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)
• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• University Hospital, Bordeaux: lead

Study Sites (1)

CHU Bordeaux - Hôpital Saint André - Department of Medical Oncology

Bordeaux, 33075, France

Location

Related Publications (3)

• 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.

  PMID: 17158539 BACKGROUND

• 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.

  PMID: 11489824 BACKGROUND

• 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.

  PMID: 15939524 BACKGROUND

MeSH Terms

Conditions

Urinary Bladder Neoplasms

Interventions

Lapatinib

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)

Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Geneviève CHENE, Pr

  USMR Bordeaux

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 18, 2010
• First Posted: November 22, 2010
• Study Start: January 1, 2011
• Primary Completion: October 1, 2011
• Study Completion: October 1, 2011
• Last Updated: January 11, 2013

Record last verified: 2013-01

Locations

FR (1)