Phase 1 study of cisplatin/hyperthermia/lapatinib in patients with previously irradiated recurrent carcinoma of the uterine cervix.

Completed

• Conditions: cervical cancer; 10038594

• Registration Number: NL-OMON36858
• Lead Sponsor: Erasmus MC, Universitair Medisch Centrum Rotterdam

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Completion: 2012-04-04
• Results First Posted: 2015-01-04
• Last Update Posted: 19 August 2024

Recruitment & Eligibility

• Status: Completed
• Sex: Not specified
• Target Recruitment: 18

Inclusion Criteria

Histologically proven pelvic recurrence of cervical cancer in previously irradiated area (with or without distant metastases), not amendable for surgery or additional radiotherapy, for which treatment with cisplatin/hyperthermia is indicated.
Age >= 18 years.
WHO performance of 0-1 and a predicted life expectancy of at least more than 12 weeks.
Adequate liver-, kidney- and bone marrow function
Left ventricular ejection fraction (LVEF) within normal range or above 50% based on MUGA/ECHO
Able to swallow and retain oral medication
Before patient registration, written informed consent must be given

Exclusion Criteria

· Prior systemic chemotherapy for recurrent tumour
· Prior treatment with lapatinib
· Pacemaker
· Artificial hip
· Pre-existing motor or sensory neurotoxicity greater than WHO grade 1
· Untreated leptomeningeal or brain metastases.
· Class II, III or IV heart failure as defined by the NYHA functional classification system
· History of congestive heart failuire, clinically significant valvular disease, or poorly controlled hypertension
· Arterial or venous thrombosis
· Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to lapatinib
· Any major surgery, hormonal therapy (other than replacement), chemotherapy or radiotherapy, immunotherapy or other investigational agent within the last 28 days and/or not recovered from prior therapy within the last 28 days have to wait 42 days before starting therapy.)
· History of malabsorption syndrome, disease significantly affecting gastrointestinal function or major resection of the stomach or small bowel that could affect absorption, distribution, metabolism or excretion of study drugs
· Any unresolved bowel obstruction or diarrhea
· Other concurrent serious disease, such as severe pulmonary conditions
· Psychological, familial, sociological, or geographical conditions that do not permit compliance with the protocol
· Is on any CYP3A4 inducing or inhibiting medication or requires any of these medications during treatment with lapatinib
· Has significant QTc prolongation (QTc interval greater than or equal to 480 msec) AND a prior history of cardiovascular disease, arrhythmias, or significant ECG abnormalities

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>To establish a MTD of lapatinib in combination with a standard dose of<br /><br>cisplatin (weekly 70 mg/m2) and local hyperthermia and to recommend a dose for<br /><br>further clinical studies</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>To assess safety and tolerability of lapatinib in combination with cisplatin<br /><br>and hyperthermia<br /><br>To describe the activity of lapatinib in combination with cisplatin and<br /><br>hyperthermia in patients with previously irradiated recurrent carcinoma of the<br /><br>uterine cervix<br /><br>Translational research: HER1/HER2 tumour tissue expression, Circulating<br /><br>endothelial cells (CEC*s), Skin-biopsy: activation of HER1/2 mediated pathways<br /><br>prior to and once during treatment.</p><br>