A phase II dose escalation study of caspofungin in patients with invasive aspergillosis - Caspofungin MTD

• Conditions: proven or probable aspergillosis in immunocompromised patients; MedDRA version: 8.1Level: LLTClassification code 10003488Term: Aspergillosis

• Registration Number: EUCTR2006-001936-30-DE
• Lead Sponsor: niversität zu Köln

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2006-10-24
• Last Update Posted: 11 February 2013

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 48

Inclusion Criteria

•Adults =18 years
•Immunocompromised due to hematologic malignancies, bone marrow failure syndromes, hematopoietic stem cell transplantation, solid organ transplantation, other conditions resulting in severe neutropenia, HIV infection, prolonged corticosteroid therapy (=20 mg Prednisone or equivalent for = 3 weeks), treatment with other immunosuppressive medications, or other immunocompromising conditions that place patients at risk for invasive fungal infections (IFIs).
•Evidence of proven or probable invasive aspergillosis, by modified EORTC criteria.
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•Female patients of childbearing age must have a negative pregnancy test at study entry and take adequate contraceptive measures throughout the study.
•Written informed consent given by the patient or his/her legal guardian prior to enrollment in the study.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

•Pregnant or breast-feeding female patients.
•Patients with the following pathological laboratory findings:
oSerum bilirubin > 3x upper limit of the age-adjusted normal range
oSGOT or SGPT > 5x the upper limit of the age-adjusted normal range
oAlkaline phosphatase > 5x the upper limit of the age-adjusted normal range
•Patients who have undergone hematopoietic stem-cell transplantation with clinical or laboratory evidence of active veno-occlusive disease (VOD). VOD is characterized by early elevation of serum transaminases and subsequent persistent elevation of serum bilirubin, tenderness of the liver, increase in body weight, and ascites.
•Hemodynamically unstable patients or patients with an expected survival time of <5 days.
•Patients previously enrolled in the study.
•Patients with concomitant diseases or conditions which, in the opinion of the principle investigator, could distort the results of the study or which could entail an additional risk for a patient receiving the study medication.
•Patients concurrently receiving efavirenz, nevirapin, rifampicin, dexamethasone, phenytoin, carbamazepine, phenobarbital or cyclosporin A. Topical use of dexamethasone, e.g. as eye drops, is allowed.
•Patients with a documented history of intolerance to echinocandin antifungal agents.
•Concomitant other systemic antifungal agents are not permitted on study.
•Chronic invasive fungal infection, defined as signs/symptoms of invasive fungal infection present for > 4 weeks preceding entry into study
•Prior systemic therapy of = 4 days with any polyene anti-fungal agent within 14 days of study enrollment
•Prior systemic therapy of = 4 days with non-polyenes (i.e., azole or echinochandin derivatives) for the current, documented IFI. (Prior systemic anti-fungal therapy with azole derivatives for prophylaxis or as empiric therapy for febrile neutropenia is permissible. Fluconazole is permissible.)

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Primary end point(s): Endpoints of safety and tolerability are the number of toxicity-related study therapy discontinuations and grade III and IV clinical and laboratory events, as evaluated on the basis of current NCI criteria;Main Objective: Endpoints of safety and tolerability are the number of toxicity-related study therapy discontinuations and grade III and IV clinical and laboratory events, as evaluated on the basis of current NCI criteria;Secondary Objective: •efficacy of caspofungin in four escalating dosages in the treatment of proven or probable invasive aspergillosis<br>•generate pharmacokinetic parameters for each dosage level