Clinical trial NCT00404092: Caspofungin Maximum Tolerated Dose in Patients With Invasive Aspergillosis
Official title: A Phase II Dose Escalation Study of Caspofungin in Patients With Invasive Aspergillosis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Invasive Aspergillosis
Keywords: aspergillosis
caspofungin
maximum tolerated dose
Lead sponsor: University of Cologne
Sponsor class: OTHER
First posted: 2006-11-27
Enrollment: 46
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study investigates the safety and tolerability as well as the efficacy and pharmacokinetics of caspofungin in four escalating dosages in adult patients with hematologic malignancies and proven or probable invasive aspergillosis.

Detailed description: Due to its efficacy and a broad antifungal spectrum against relevant fungal pathogens, lack of cross-resistance to azoles and amphotericin B, documented efficacy against human Aspergillus infections, favorable pharmacokinetic properties, and excellent tolerability according to the current data, caspofungin is a highly promising candidate for improving the results of treatment of invasive fungal infections.

Preclinical and clinical data indicate a dose dependent antifungal efficacy of caspofungin as well as of other echinocandins such as micafungin and anidulafungin. Thus it appears reasonable to investigate the impact of higher doses of caspofungin to improve the results already achieved with this component so far.

The maximum tolerated dose (MTD) of caspofungin and the distribution of the drug in patients following administration of doses of 70 mg or more are not yet known. We therefore investigate the safety, tolerability and pharmacokinetics of caspofungin in rising doses in a dose escalation study in adult patients with proven or probable invasive aspergillosis.

Eligibility criteria: Inclusion Criteria:

* 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, treatment with other immunosuppressive medications, or other immunocompromising conditions that place patients at risk for invasive fungal infections.
* Evidence of proven or probable invasive aspergillosis, by modified EORTC criteria

Exclusion Criteria:

* 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 for the current, documented IFI.

Primary outcomes:
measure: Safety and Tolerability of Caspofungin in Four Escalating Dosages in Adult Patients With Hematologic Malignancies and Proven or Probable Invasive Aspergillosis
timeFrame: End of caspofungin treatment, treatment duration varied between 3 and 29 days (mean: 20.5; median: 24.5)
Secondary outcomes:
measure: Efficacy of Caspofungin in Four Escalating Dosages in the Treatment of Proven or Probable Invasive Aspergillosis.
timeFrame: End of caspofungin treatment; 4 weeks follow-up; 12 weeks follow-up
Other outcomes:
Locations:
city: Leuven
country: Belgium
facility: University Hospital Gasthuisberg
city: Berlin
country: Germany
facility: Charité - Campus Benjamin Franklin
city: Köln
country: Germany
facility: Klinikum der Universität zu Köln
city: Münster
country: Germany
facility: Universitätsklinikum Münster
Study officials:
affiliation: Klinikum der Universität zu Köln
name: Oliver A. Cornely, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Cornely OA, Vehreschild JJ, Vehreschild MJ, Wurthwein G, Arenz D, Schwartz S, Heussel CP, Silling G, Mahne M, Franklin J, Harnischmacher U, Wilkens A, Farowski F, Karthaus M, Lehrnbecher T, Ullmann AJ, Hallek M, Groll AH. Phase II dose escalation study of caspofungin for invasive Aspergillosis. Antimicrob Agents Chemother. 2011 Dec;55(12):5798-803. doi: 10.1128/AAC.05134-11. Epub 2011 Sep 12.
citation: Wurthwein G, Cornely OA, Trame MN, Vehreschild JJ, Vehreschild MJ, Farowski F, Muller C, Boos J, Hempel G, Hallek M, Groll AH. Population pharmacokinetics of escalating doses of caspofungin in a phase II study of patients with invasive aspergillosis. Antimicrob Agents Chemother. 2013 Apr;57(4):1664-71. doi: 10.1128/AAC.01912-12. Epub 2013 Jan 18.