ototoxicity
Conditions
Interventions
Arm A
In order to prevent the development of ototoxicity STS containing transtympanic
injections will be applied three hours prior to each first administration of
cisplatin treatment in each cycle.
Sponsors
Antoni van Leeuwenhoek Ziekenhuis
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: 1. Histological or cytological proof of advanced cancer for which cisplatin treatment at a minimal dose of 75 mg/m2 per 21 days is considered of benefit; for example non-small cell lung cancer; patients with a head and neck malignancy of the oropharynx, hypofarynx, oral cavity and larynx with blue or brown eyes. 2. Age * 18 years; 3. Able and willing to give written informed consent; 4. WHO performance status of 0, 1 or 2; 5. No relevant otological history; (presbyacusis, conductive hearing loss, air-bone gap (ABG), complaints of tinnitus or vertigo, ototoxic co-medication (see appendix VI), chronic middle ear infections, trauma, operations, or hearing aid) , 6. Able and willing to undergo blood sampling for PK analysis and genetic analysis for specific SNPs; 7. Minimal acceptable safety laboratory values; a. ANC of * 1.5 x 109 /L b. Platelet count of * 100 x 109 /L c. Hepatic function as defined by serum bilirubin * 1.5 x ULN, ALAT and ASAT * 2.5 x ULN or *5 x ULN in case of liver metastases d. Renal function as defined by serum creatinine * 2.5 x ULN or creatinine clearance * 60 ml/min (by Cockcroft-Gault formula). 8. Negative pregnancy test (urine/serum) for female patients with childbearing potential; 9. Combined treatment of cisplatin with other cytostatic, cytotoxic or radiation therapy according to local treatment guidelines is permitted. However, radiation therapy to the head and neck region is excluded.
Exclusion criteria
Exclusion criteria: 1. Any treatment with investigational drugs or other antineoplastic therapy within 21 days prior to receiving the first dose of investigational treatment; 2. Patients who have had previous systemic treatment with cisplatin or oxaliplatin; (HIPEC and other local non systemic therapy are allowed) 3. Known hypersensitivity to STS containing HYA gel formulation; 4. Patients with symptomatic brain metastases, carcinomatous leptomeningitis at start; 5. Woman who are pregnant or breast feeding; 6. Uncontrolled infectious disease or known Human Immunodeficiency Virus HIV-1 or HIV-2 type patients; 7. Patients with a known history of hepatitis B or C; 8. Patients with a head and neck malignancy other than; oropharynx, hypopharynx, oral cavity and larynx or patients with a head and neck malignancy green eyes. 9. Any condition that would, in the investigator judgement contraindicate the patients participation in the clinical study due to safety concerns or compliance with clinical study procedures
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Audiometric tests after each cycle will be compared to baseline audiometric tests to measure the development of the occurence of ototoxicity and 4 weeks en 3 months after the last cycle of cisplatin. | — |
Secondary
| Measure | Time frame |
|---|---|
| To determine the feasibility and safety of repeated application of a STS containing or placebo gel formulation to the middle ear through a grommet (arm A) To determine the feasibility and safety of repeated application of STS containing gel formulation by direct puncture of the ear drum (arm B). To determine the pharmacokinetics of platinum in plasma (bound and unbound) in these patients. On exploratory basis patients will be screened for genetic variants in the TPMT, COMT, LRP2, GSTP1, GSTM1 and OCT2. Previous prospective studies performed and prescirbed in literature have shown a possible relation of genetic variations in these genes to the development of ototoxicity in patients treated with cisplatin. | — |
Countries
Netherlands
Outcome results
None listed