Caspofungin Maximum Tolerated Dose in Patients With Invasive Aspergillosis

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Oliver Cornely, MD, University of Cologne
ClinicalTrials.gov Identifier:
NCT00404092
First received: November 24, 2006
Last updated: July 25, 2013
Last verified: July 2013
  Purpose

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.


Condition Intervention Phase
Invasive Aspergillosis
Drug: caspofungin
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Dose Escalation Study of Caspofungin in Patients With Invasive Aspergillosis

Resource links provided by NLM:


Further study details as provided by University of Cologne:

Primary Outcome Measures:
  • 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) ] [ Designated as safety issue: Yes ]
    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:
  • 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 ] [ Designated as safety issue: No ]

    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.



Enrollment: 46
Study Start Date: October 2006
Study Completion Date: October 2009
Primary Completion Date: October 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1st cohort
70mg caspofungin 1x/day
Drug: caspofungin
i.v.
Other Name: cancidas
Experimental: 2nd cohort
100mg caspofungin 1x/day
Drug: caspofungin
i.v.
Other Name: cancidas
Experimental: 3rd cohort
150mg caspofungin 1x/day
Drug: caspofungin
i.v.
Other Name: cancidas
Experimental: 4th cohort
200mg caspofungin 1x/day
Drug: caspofungin
i.v.
Other Name: cancidas

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00404092

Locations
Belgium
University Hospital Gasthuisberg
Leuven, Belgium, 3000
Germany
Charité - Campus Benjamin Franklin
Berlin, Germany, 12200
Klinikum der Universität zu Köln
Köln, Germany, 50924
Universitätsklinikum Münster
Münster, Germany, 48149
Sponsors and Collaborators
University of Cologne
Investigators
Principal Investigator: Oliver A. Cornely, MD Klinikum der Universität zu Köln
  More Information

Publications:
Responsible Party: Oliver Cornely, MD, Prof. Dr. Oliver Cornely, University of Cologne
ClinicalTrials.gov Identifier: NCT00404092     History of Changes
Other Study ID Numbers: Uni-Koeln-687, 2006-001936-30
Study First Received: November 24, 2006
Results First Received: December 12, 2012
Last Updated: July 25, 2013
Health Authority: Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by University of Cologne:
aspergillosis
caspofungin
maximum tolerated dose

Additional relevant MeSH terms:
Aspergillosis
Hyalohyphomycosis
Dermatomycoses
Skin Diseases, Infectious
Infection
Mycoses
Skin Diseases
Caspofungin
Echinocandins
Antifungal Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on September 18, 2014