cervical cancer
Conditions
Interventions
Weekly hyperthermia combined with weekly cisplatin intravenously given at a
dose of 70 mg/m2 in combination with escalating dose of daily continuous
lapatinib for a total treatment period of 6 weeks
Sponsors
Erasmus MC, Universitair Medisch Centrum Rotterdam
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
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
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To establish a MTD of lapatinib in combination with a standard dose of cisplatin (weekly 70 mg/m2) and local hyperthermia and to recommend a dose for further clinical studies | — |
Secondary
| Measure | Time frame |
|---|---|
| To assess safety and tolerability of lapatinib in combination with cisplatin and hyperthermia To describe the activity of lapatinib in combination with cisplatin and hyperthermia in patients with previously irradiated recurrent carcinoma of the uterine cervix Translational research: HER1/HER2 tumour tissue expression, Circulating endothelial cells (CEC*s), Skin-biopsy: activation of HER1/2 mediated pathways prior to and once during treatment. | — |
Countries
Netherlands
Outcome results
None listed