Clinical Trial: Caspofungin Maximum Tolerated Dose in Patients With Invasive Aspergillosis

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

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

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 Summary:

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.


Sponsor: University of Cologne

Current Primary Outcome: Safety and Tolerability of Caspofungin in Four Escalating Dosages in Adult Patients With Hematologic Malignancies and Proven or Probable Invasive Aspergillosis [ Time Frame: 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.


Original Primary Outcome: safety and tolerability of caspofungin in four escalating dosages defined as number of toxicity-related study therapy discontinuations and grade III and IV clinical and laboratory events

Current Secondary Outcome: Efficacy of Caspofungin in Four Escalating Dosages in the Treatment of Proven or Probable Invasive Aspergillosis. [ Time Frame: 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.



Original Secondary Outcome:

  • efficacy of caspofungin in four escalating dosages
  • pharmacokinetics of caspofungin in four escalating dosages


Information By: University of Cologne

Dates:
Date Received: November 24, 2006
Date Started: October 2006
Date Completion:
Last Updated: July 25, 2013
Last Verified: July 2013