Lapatinib, Cisplatin, Gemcitabine as First-Line Therapy in Treating Patients With Locally Advanced or Metastatic Urothelial Cancer

NCT00623064 | Completed Phase 1

• 3 other identifiers: EORTC-30061EUDRACT-2006-002976-16GSK-EORTC-30061
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

RATIONALE: Lapatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as cisplatin, and gemcitabine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving lapatinib together with combination chemotherapy may kill more tumor cells. PURPOSE: This phase I trial is studying the side effects and best dose of lapatinib when given together with cisplatin and gemcitabine as first-line therapy in treating patients with locally advanced or metastatic urothelial cancer.

Conditions

Bladder Cancer; Transitional Cell Cancer of the Renal Pelvis and Ureter

Keywords

transitional cell carcinoma of the bladder; stage IV bladder cancer; stage III bladder cancer; metastatic transitional cell cancer of the renal pelvis and ureter; regional transitional cell cancer of the renal pelvis and ureter

Outcome Measures

Primary Outcomes (1)

• Maximum tolerated dose of lapatinib ditosylate in combination with cisplatin/gemcitabine hydrochloride and cisplatin/gemcitabine hydrochloride based on the documentation of the acute dose-limiting toxicity in course 1

Secondary Outcomes (2)

• Pharmacokinetic profile of lapatinib ditosylate in combination with cisplatin/gemcitabine hydrochloride and cisplatin/gemcitabine hydrochloride

• Antitumor activity according to RECIST

Interventions

cisplatin DRUG

gemcitabine hydrochloride DRUG

lapatinib ditosylate DRUG

pharmacological study OTHER

Eligibility Criteria

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

DISEASE CHARACTERISTICS: * Histologically proven transitional cell carcinoma of the urothelial tract * Metastatic or locally advanced disease * Measurable disease according to RECIST * Involvement of at least one target not in previously irradiated fields * Overexpressing HER1 and/or HER2 receptors (HER2 3+ by IHC OR HER2 FISH or CISH positive) * No clinical signs of CNS involvement PATIENT CHARACTERISTICS: * WHO performance status 0-1 * ANC ≥ 1,500/mm³ * Thrombocytes \> 100,000/mm³ * Bilirubin ≤ 1.5 times upper limit of normal (ULN) * AST/ALT ≤ 3 times ULN * Creatinine clearance ≥ 60 mL/min * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective double-barrier contraception during and for 3 months after completion of study treatment * Cardiac ejection fraction normal * Normal 12 lead ECG * No serious cardiac illness or medical condition within the past 6 months including, but not limited to, any of the following: * Documented congestive heart failure * High-risk uncontrolled arrhythmias * Angina pectoris requiring antianginal medication * Clinically significant valvular heart disease * Evidence of transmural infarction on ECG * Poorly controlled hypertension (e.g., systolic blood pressure \[BP\] \> 180 mm Hg or diastolic BP \> 100 mm Hg) * No peripheral neuropathy \> grade 1 * Able to swallow and retain oral medication * No other malignancy within the past 3 years except basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix * No active or uncontrolled infections, serious illnesses, malabsorption syndrome or medical conditions, hepatitis, HIV, and/or cirrhosis * No psychological, familial, sociological, or geographical condition potentially hampering study protocol compliance or follow-up schedule * No current active hepatic or biliary disease (with the exception of Gilbert's syndrome, asymptomatic gallstones, liver metastases or stable chronic liver metastases or stable chronic liver disease) PRIOR CONCURRENT THERAPY: * Recovered from any effects of surgery * Intravesicle therapy for superficial disease allowed * Prior neoadjuvant or adjuvant chemotherapy allowed * Must have a minimum interval of six months between the completion of neoadjuvant or adjuvant chemotherapy and the diagnosis of metastatic disease * No prior chemotherapy for metastatic disease * No radiotherapy within the past 4 weeks * No drugs and herbal inducers or inhibitors of CYP3A4 (e.g., bergamottin or glabridin) within 10 days prior to study treatment and while receiving lapatinib ditosylate therapy * No other concurrent anticancer therapy or investigational agents * No other concurrent anticancer agents * No concurrent treatment with other investigational therapy for other diseases or conditions * No concurrent prophylactic antibiotics * No concurrent prophylactic filgrastim (G-CSF) * At least 14 days since prior and no concurrent herbal or dietary supplements * No concurrent consumption of grapefruit juice

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• European Organisation for Research and Treatment of Cancer - EORTC: lead

Study Sites (1)

Rigshospitalet - Copenhagen University Hospital

Copenhagen, 2100, Denmark

Location

MeSH Terms

Conditions

Urinary Bladder Neoplasms

Interventions

Cisplatin; Gemcitabine; 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)

Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Gedske Daugaard, MD, DMSc

  Rigshospitalet, Denmark

  STUDY CHAIR

Study Design

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

Study Record Dates

• First Submitted: February 22, 2008
• First Posted: February 25, 2008
• Study Start: November 1, 2007
• Primary Completion: June 1, 2012
• Study Completion: August 1, 2012
• Last Updated: July 1, 2014

Record last verified: 2014-06

Locations

DK (1)