Voriconazole and Caspofungin Acetate in Treating Invasive Fungal Infections in Patients With Weakened Immune Systems

Phase II Trial of Voriconazole Plus Caspofungin for the Initial Treatment of Invasive Fungal Infections

RATIONALE: Voriconazole and caspofungin acetate may control invasive fungal infections in patients who have weakened immune systems.

PURPOSE: This phase II trial is studying how well giving voriconazole together with caspofungin acetate works in treating invasive fungal infections in patients with weakened immune systems.

Study Overview

• Status: Terminated
• Conditions: Unspecified Adult Solid Tumor, Protocol Specific; Infection
• Intervention / Treatment: Drug: caspofungin acetate; Drug: voriconazole

Detailed Description

OBJECTIVES:

Primary

• Determine the 12-week complete and partial response rate in immunocompromised patients with invasive fungal infections treated with voriconazole and caspofungin acetate.

Secondary

• Determine the 12-week survival rate in patients treated with this regimen.
• Determine the safety of this regimen in these patients.

OUTLINE: Patients receive voriconazole orally or IV over 1 hour twice daily and caspofungin acetate IV over 1 hour once daily on days 1-84. Treatment continues in the absence of disease progression or unacceptable toxicity.

PROJECTED ACCRUAL: A total of 47 patients will be accrued for this study.

• Study Type: Interventional
• Enrollment (Actual): 13
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Oregon
    • Portland, Oregon, United States, 97239-3098
      • OHSU Knight Cancer Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

DISEASE CHARACTERISTICS:

• Diagnosis of probable or definite invasive fungal infection with 1 of the following organisms:

  • Aspergillus species
  • Fusarium species
  • Scedosporium species (Pseudallescheria boydii)
  • Other dematiaceous molds

• The following diagnosis are not allowed:

  • Zygomycetes (Mucor or Rhizopus species)
  • Chronic aspergillosis
  • Aspergilloma
  • Allergic bronchopulmonary aspergillosis
• Must be immunocompromised

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• Not specified

Life expectancy

• At least 72 hours

Hematopoietic

• Not specified

Hepatic

• AST < 5 times upper limit of normal (ULN)
• Bilirubin < 5 times ULN
• Alkaline phosphatase < 5 times ULN
• No Child-Pugh class C cirrhosis

Renal

• Creatinine clearance ≥ 50 mL/min

Pulmonary

• No mechanical ventilation

Other

• Not pregnant or nursing
• Fertile patients must use effective contraception
• No hypersensitivity to azoles, caspofungin acetate, or their components
• No history of galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Not specified

Chemotherapy

• Not specified

Endocrine therapy

• Not specified

Radiotherapy

• Not specified

Surgery

• Not specified

Other

• More than 14 days since prior therapeutic antifungal therapy of ≥ 1 week duration

• More than 14 days since prior and no concurrent administration of any of the following medications:

  • Terfenadine
  • Astemizole
  • Cisapride
  • Pimozide
  • Quinidine
  • Sirolimus
  • Rifampin
  • Carbamazepine
  • Long-acting barbiturates
  • Rifabutin
  • Ergot alkaloids (i.e., ergotamine and dihydroergotamine)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: SUPPORTIVE_CARE
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Voriconazole plus Caspofungin	Drug: caspofungin acetate; 70 mg iv x 1 on day 1 (loading dose), followed by 50 mg iv daily on day 2 through day 84.; Drug: voriconazole; 6mg/kg iv q12 hours x 2 doses OR 400mg po q12hours on day 1 (loading doses. Maintenance doses on day 2 through day 84 may be either 4 mg/kg iv q12 hours, or 200 mg po q12 hours (at least one hour before or after meals).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With a Complete or Partial Response Rate to the Combination of Voriconazole and Caspofungin at 12 Weeks.	Patients will be followed through day 84 (12 weeks), regardless of continuation of study drugs. Complete response: Resolution of all clinical signs and symptoms and more than 90 percent of the lesions due to invasive fungus that were visible by radiology. Partial response: Clinical improvement and greater than 50 percent improvement in the lesions due to invasive fungus that were visible by radiology.	12 weeks after starting treatment

Secondary Outcome Measures

Outcome Measure	Time Frame
Duration of Survival up to 12 Weeks	up to 12 weeks
Safety	duration of study

Collaborators and Investigators

• Sponsor: OHSU Knight Cancer Institute
• Collaborators: National Cancer Institute (NCI)
• Investigators: Study Chair: Lynne Strasfeld, MD, OHSU Knight Cancer Institute

Study record dates

Study Major Dates

• Study Start: August 1, 2003
• Primary Completion (ACTUAL): June 1, 2008
• Study Completion (ACTUAL): June 1, 2008

Study Registration Dates

• First Submitted: October 12, 2005
• First Submitted That Met QC Criteria: October 12, 2005
• First Posted (ESTIMATE): October 13, 2005

Study Record Updates

• Last Update Posted (ESTIMATE): December 19, 2011
• Last Update Submitted That Met QC Criteria: December 12, 2011
• Last Verified: December 1, 2011

More Information

Terms related to this study

• Keywords: unspecified adult solid tumor, protocol specific; infection
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Bacterial Infections and Mycoses; Infections; Communicable Diseases; Mycoses; Invasive Fungal Infections; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Hormones, Hormone Substitutes, and Hormone Antagonists; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Hormone Antagonists; Antifungal Agents; Steroid Synthesis Inhibitors; 14-alpha Demethylase Inhibitors; Caspofungin; Voriconazole
• Other Study ID Numbers: CDR0000445848; OHSU-HEM-0346-L (OTHER: OHSU Knight Cancer Institute); OHSU-IRB-1379 (OTHER: OHSU IRB)