An Open-Label, Phase I Study to Evaluate the Pharmacokinetics and Tolerance of Co-administration of Oral Multiple Dose of Ketoconazole and an IV (bolus) Infusion of Eribulin in Patients with Advanced Solid Tumors

• Conditions: Cancer; Drug Metabolism; 10027656

• Registration Number: NL-OMON33694
• Lead Sponsor: Eisai

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Last Update Posted: 13 May 2024

Recruitment & Eligibility

• Status: Pending
• Sex: Not specified
• Target Recruitment: 12

Inclusion Criteria

1. Patients must have a histologically or cytologically confirmed solid tumour in an advanced stage that showed progression when standard therapy was followed or for which there is no standard therapy (including surgery or radiotherapy).
2. Resolution of all chemotherapy- or radiotherapy-related toxicities with a severity of class 1 or lower, except for stable sensory neuropathy <= class 2 and alopecia.
3. Patients must be >= 18 years old.
4. An Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1 or 2.
5. A life expectancy of >= 3 months.
6. Patients must have adequate renal function that must be apparent from serum creatinine <= 2.0 mg/dl (<= 176 µmol/l) or calculated creatinine clearance >= 40 ml/minute (min) according to the Cockcroft and Gault formula.
7. Patients must have adequate hepatic function that must be apparent from bilirubin <= 1.5 times the upper limit of normal (ULN) and alkaline phosphatase, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) <= 3 times the ULN, (in the case of liver metastases <= 5 times the ULN or in the case of bone metastases, the liver-specific alkaline phosphatase <= 3 times the ULN).
8. Patients must have adequate bone marrow function as demonstrated by means of absolute neutrophil count (ANC) >= 1.5 x 109/l, haemoglobin >= 10.0 g/dl or >= 6.2 mmol/l (a haemoglobin < 10.0 g/dl or < 6,2 mmol/l is acceptable if it is corrected by growth factor or transfusion) and blood platelets >= 100 x 109/l.
9. Patients must be willing and able to keep to the study protocol for the duration of the study.
10. Prior to any study-specific screening procedures whatsoever, patients must give written consent after receipt of information, on condition that the patient may withdraw his consent at any time without this having any consequences.

Exclusion Criteria

1. Patients who have received any of the following treatments within the specified period before the start of treatment with eribulin:
a) Chemotherapy, radiotherapy or biological therapy within 2 weeks.
b) Hormonal treatment within 1 week.
c) Any study drug whatsoever within 4 weeks.
2. Patients receiving anticoagulant therapy with warfarin or related compounds, other than for good flow in the infusion line and who cannot be switched to heparin-based treatment cannot be considered. If a patient has to remain on a minidose of warfarin, the prothrombin time (PT) or international normalised ratio (INR) must be closely monitored.
3. Patients who at the time of the start of the study are receiving any medication, food supplements or other compounds or substances known to induce or inhibit the effect of CYP3A4, with the exception of ketoconazole.
4. Patients for whom the use of ketoconazole is contraindicated.
5. Patients receiving medications that might influence the metabolism of ketoconazole.
6. Pregnant or breast-feeding women; women of child-bearing age with a positive pregnancy test during screening or without a pregnancy test; women of child-bearing age unless (1) they have been surgically sterilised or (2) in the opinion of the investigator are taking adequate contraceptive measures. To be able to say of women that they are unable to have children, women who are perimenopausal must have been amenorrhoeic for at least 12 months.
7. Fertile men who are not willing to use contraception or fertile men with a female partner who is not willing to use contraception.
8. Patients whose intestinal absorption is affected.
9. Severe/uncontrolled intercurrent disease/infection.
10. Significant poor cardiovascular condition (history of congestive heart failure > New York Heart Association (NYHA) Class II, unstable angina or myocardial infarction in the last 6 months, or severe cardiac arrhythmia.
11. Patients with allogenic organ transplants who needed immunosuppression (with the exception of blood and blood component transfusions).
12. Patients with known positive human immunodeficiency virus (HIV) status.
13. Patients with brain or subdural metastases cannot be considered unless they have finished local treatment and have stopped the use of corticosteroids for this indication for at least 4 weeks before the start of treatment with eribulin.
14. Patients with meningeal carcinomatosis.
15. Patients with hypersensitivity to halichondrin B and/or halichondrin B-like compounds.
16. Patients with already existing neuropathy > Class 2.
17. Patients with other significant disease or disorders which, in the investigator*s opinion, might exclude the patient from the study.

Study & Design

• Study Type: Interventional
• Study Design: Not specified