Caspofungin Maximum Tolerated Dose in Patients With Invasive Aspergillosis

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Invasive Aspergillosis

Intervention / Treatment
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* Drug: caspofungin


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1st cohort<br>70mg caspofungin 1x/day | Drug: caspofungin<br>* i.v.<br>* Other names: cancidas;|
| Experimental: 2nd cohort<br>100mg caspofungin 1x/day | Drug: caspofungin<br>* i.v.<br>* Other names: cancidas;|
| Experimental: 3rd cohort<br>150mg caspofungin 1x/day | Drug: caspofungin<br>* i.v.<br>* Other names: cancidas;|
| Experimental: 4th cohort<br>200mg caspofungin 1x/day | Drug: caspofungin<br>* i.v.<br>* Other names: cancidas;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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aspergillosis, caspofungin, maximum tolerated dose