Caspofungin Maximum Tolerated Dose in Patients With Invasive Aspergillosis

Phase 2

Completed

• Conditions: Invasive Aspergillosis
• Interventions: Drug: caspofungin

• Registration Number: NCT00404092
• Lead Sponsor: University of Cologne

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.

Study Timeline

• Study Start: 2006-10
• Study First Submitted: 2006-11-24
• Study First Submitted QC: 2006-11-24
• Study First Posted: 2006-11-27
• Primary Completion: 2009-10
• Study Completion: 2009-10
• Results First Submitted: 2012-12-12
• Results First Submitted QC: 2012-12-12
• Results First Posted: 2013-01-21
• Status Verified: 2013-07
• Last Update Submitted: 2013-07-25
• Last Update Posted: 2013-07-31

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 46

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

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
2nd cohort	caspofungin	100mg caspofungin 1x/day
1st cohort	caspofungin	70mg caspofungin 1x/day
3rd cohort	caspofungin	150mg caspofungin 1x/day
4th cohort	caspofungin	200mg caspofungin 1x/day

Primary Outcome Measures

Name	Time	Method
Safety and Tolerability of Caspofungin in Four Escalating Dosages in Adult Patients With Hematologic Malignancies and Proven or Probable Invasive Aspergillosis	End of caspofungin treatment, treatment duration varied between 3 and 29 days (mean: 20.5; median: 24.5)	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 Outcome Measures

Name	Time	Method
Efficacy of Caspofungin in Four Escalating Dosages in the Treatment of Proven or Probable Invasive Aspergillosis.	End of caspofungin treatment; 4 weeks follow-up; 12 weeks follow-up	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.

Trial Locations

Locations (4)

University Hospital Gasthuisberg; 🇧🇪 Leuven, Belgium

Klinikum der Universität zu Köln; 🇩🇪 Köln, Germany

Charité - Campus Benjamin Franklin; 🇩🇪 Berlin, Germany

Universitätsklinikum Münster; 🇩🇪 Münster, Germany