Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Trial Contact Information
Registry Information

Alternate Title

Comparison of Voriconazole and Amphotericin B in Treating Patients With Aspergillosis

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase III Supportive care Closed 12 and over Pharmaceutical / Industry EORTC-19961 PFIZER-150-307-000, NCT00003031

Objectives

I.  Compare the efficacy, safety, and toleration of voriconazole versus 
amphotericin B (CAB) in the treatment of acute invasive aspergillosis in 
immunocompromised patients.

II.  Compare the efficacy, safety, and toleration of voriconazole versus CAB 
followed by other antifungal therapy in the treatment of acute invasive 
aspergillosis in immunocompromised patients.

III.  Compare survival in patients treated with voriconazole versus CAB with 
or without other antifungal therapy.

IV.  Investigate resource utilization in patients treated with voriconazole 
versus CAB with or without other antifungal therapy.

Entry Criteria

Disease Characteristics:

Patient immunocompromised as the result of any of the following:
 Allogeneic bone marrow/peripheral stem cell transplant
 Autologous bone marrow/peripheral stem cell transplant
 Hematological malignancy (including lymphoma)
 Aplastic anemia and myelodysplastic syndromes (currently on immunosuppressive
  treatment)
 Solid organ transplantation (other than lung)
 Other solid organ malignancy (after cytotoxic chemotherapy)
 HIV/AIDS
 High dose prolonged corticosteroid therapy (at least 20 mg/day of
  prednisolone or equivalent for more than 3 weeks) or prolonged therapy with
  other immunosuppressive agents (e.g., azathioprine, methotrexate)

Diagnosis of either definite or probable acute invasive aspergillosis 

Fungal infection represents a new episode of acute invasive aspergillosis

Patients with the following are ineligible:
 Aspergilloma or allergic bronchopulmonary aspergillosis
 Chronic invasive aspergillosis
 Sarcoidosis
 CMV pneumonia

Prior/Concurrent Therapy:

At least 8 weeks since prior systemic treatment with amphotericin B or
 itraconazole 
At least 2 weeks since prior systemic antifungal therapy for more than 96
 hours at doses greater than 0.5 mg/kg/day for conventional or lipid
 formulations of amphotericin B or greater than 200 mg/day of itraconazole 
No concurrent drugs that are metabolized primarily by hepatic cytochrome P-450
 enzymes or which induce or inhibit these enzymes, such as terfenadine,
 loratidine, astemizole, midazolam, triazolam, cisapride, rifampin,
 rifabutin, barbiturates, carbamazepine, coumarins, sulfonylureas, nivarapine,
 erythromycin, ritonavir, delaviridine, omeprazole, and phenytoin
At least 2 weeks since prior rifampin, rifabutin, carbamazepine, or
 barbiturates for more than 3 days
No concurrent investigational drugs other than cytotoxics, antiretroviral
 agents, or therapies for AIDS-related opportunistic infection
No concurrent filgrastim (G-CSF) or sargramostim (GM-CSF) other than for
 treatment of granulocytopenia
No concurrent white blood cell transfusions
No concurrent systemic antifungal agents active against Aspergillus spp.
 (e.g., itraconazole, lipid formulations of amphotericin B, or flucytosine)

Patient Characteristics:

Age:
 12 and over

Life expectancy:
 At least 72 hours

Hematopoietic:
 Not specified

Hepatic:
 Bilirubin no greater than 5 times upper limit of normal (ULN)
 SGOT/SGPT no greater than 5 times ULN
 Alkaline phosphatase no greater than 5 times ULN

Renal:
 Creatinine no greater than 2.5 mg/dL

Other:
 No history of hypersensitivity or intolerance to azole antifungal agents
  including miconazole, ketoconazole, fluconazole, or itraconazole
 No history of hypersensitivity or severe intolerance to conventional or lipid
  formulations of amphotericin B
 Not pregnant or nursing
 Fertile women must use effective contraception 
 Negative pregnancy test
 No prior participation on this trial
 Not on artificial ventilation and unlikely to be extubated within 24 hours
 No condition that could affect patient safety, preclude evaluation of
  response, or make study completion unlikely

Expected Enrollment

A sufficient number of patients will be accrued so that 212 patients (106 per 
study arm) will be eligible for the study.

Outline

This is an open label, randomized, multicenter study.  Patients are stratified 
according to center, site of infection, underlying disease, and baseline 
neutrophil count.

Patients are randomized to one of two treatment arms.

Arm I: Patients receive voriconazole IV every 12 hours for 7-28 days and 
continue with oral voriconazole twice a day for a maximum total duration of 12 
weeks of therapy.

Arm II: Patients receive intravenous amphotericin B daily for at least 2 
weeks; treatment continues for a maximum of 12 weeks.

Patients discontinued from study drug treatment because of toxicity, 
intolerance or clinical failure may receive alternative (nonstudy) antifungal 
therapy.  All patients are monitored for a total of 16 weeks.

Trial Contact Information

Trial Lead Organizations

European Organization for Research and Treatment of Cancer

R. Herbrecht, MD, Protocol chair		Ph: 33-388-127-688 Email: raoul.herbrecht@chru-strasbourg.fr

Registry Information
Official Title		An Open Randomised Comparative Multicentre Study of the Efficacy, Safety and Toleration of Voriconazole Versus Amphotericin-B in the Treatment of Acute Invasive Aspergillosis in Immunocompromised Patients
Trial Start Date		1997-06-01
Registered in ClinicalTrials.gov		NCT00003031
Date Submitted to PDQ		1997-06-01
Information Last Verified		2007-05-14