Caspofungin Maximum Tolerated Dose in Patients With Invasive Aspergillosis

Invasive Aspergillosis Clinical Trial

Official title:

A Phase II Dose Escalation Study of Caspofungin in Patients With Invasive Aspergillosis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00404092
• Other study ID #: Uni-Koeln-687
• Secondary ID: 2006-001936-30
• Status: Completed
• Phase: Phase 2
• First received: November 24, 2006
• Last updated: July 25, 2013
• Start date: October 2006
• Est. completion date: October 2009

Study information

• Verified date: July 2013
• Source: University of Cologne
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Federal Institute for Drugs and Medical Devices
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 46
• Est. completion date: October 2009
• Est. primary completion date: October 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Aspergillosis
• Invasive Aspergillosis

Intervention

Drug:
• caspofungin
i.v.

Locations

Country	Name	City	State
Belgium	University Hospital Gasthuisberg	Leuven
Germany	Charité - Campus Benjamin Franklin	Berlin
Germany	Klinikum der Universität zu Köln	Köln
Germany	Universitätsklinikum Münster	Münster

Sponsors (1)

Lead Sponsor	Collaborator
University of Cologne

Countries where clinical trial is conducted

Belgium,  Germany, 

References & Publications (2)

Cornely OA, Vehreschild JJ, Vehreschild MJ, Würthwein 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 — View Citation

Würthwein G, Cornely OA, Trame MN, Vehreschild JJ, Vehreschild MJ, Farowski F, Müller 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. Anti — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety and Tolerability of Caspofungin in Four Escalating Dosages in Adult Patients With Hematologic Malignancies and Proven or Probable Invasive Aspergillosis	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.	End of caspofungin treatment, treatment duration varied between 3 and 29 days (mean: 20.5; median: 24.5)	Yes
Secondary	Efficacy of Caspofungin in Four Escalating Dosages in the Treatment of Proven or Probable Invasive Aspergillosis.	Numbers of patients in each dose cohort according to invasive aspergillosis (IA) outcome at end of protocol treatment (EOT), 4 weeks follow-up (4w FU) and 12 weeks follow-up (12w FU), respectively. 12w FU was only required for patients with a CR or PR at the 4w FU.; Definitions: CR: resolution of all attributable symptoms, signs, and radiographic or bronchoscopic abnormalities.; PR: clinically meaningful improvement in attributable symptoms, signs, and radiographic (min. 50% decrease) or bronchoscopic abnormalities.; Stable disease (SD): no improvement in attributable symptoms, signs, and radiographic or bronchoscopic abnormalities.; Failure: deterioration in attributable clinical or radiographic abnormalities necessitating alternative antifungal therapy or resulting in death.; Relapse: reemergence of IA after EOT following CR, PR or SD or early withdrawal.	End of caspofungin treatment; 4 weeks follow-up; 12 weeks follow-up	No