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

• Sponsor: OHSU Knight Cancer Institute (Other)
• Overall Status: Terminated
• CT.gov ID: NCT00238355
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 13
• Location: 1
• Arm: 1
• Duration (Months): 58
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Infection; Unspecified Adult Solid Tumor, Protocol Specific	Drug: caspofungin acetate; Drug: voriconazole	Phase 2

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 Design

• Study Type: Interventional
• Actual Enrollment: 13 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Supportive Care
• Official Title: Phase II Trial of Voriconazole Plus Caspofungin for the Initial Treatment of Invasive Fungal Infections
• Study Start Date: Aug 1, 2003
• Actual Primary Completion Date: Jun 1, 2008
• Actual Study Completion Date: Jun 1, 2008

Arms and Interventions

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).

Outcome Measures

Primary Outcome Measures

1. Number of Participants With a Complete or Partial Response Rate to the Combination of Voriconazole and Caspofungin at 12 Weeks. [12 weeks after starting treatment]

   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.

Secondary Outcome Measures

1. Duration of Survival up to 12 Weeks [up to 12 weeks]

2. Safety [duration of study]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	OHSU Knight Cancer Institute	Portland	Oregon	United States	97239-3098

Sponsors and Collaborators

• OHSU Knight Cancer Institute
• National Cancer Institute (NCI)

Investigators

• Study Chair: Lynne Strasfeld, MD, OHSU Knight Cancer Institute

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: OHSU Knight Cancer Institute
• ClinicalTrials.gov Identifier: NCT00238355
• Other Study ID Numbers: CDR0000445848; OHSU-HEM-0346-L; OHSU-IRB-1379
• First Posted: Oct 13, 2005
• Last Update Posted: Dec 19, 2011
• Last Verified: Dec 1, 2011

• Keywords provided by OHSU Knight Cancer Institute: infection; unspecified adult solid tumor, protocol specific
• Additional relevant MeSH terms: Infections; Communicable Diseases; Mycoses; Invasive Fungal Infections; Voriconazole; Caspofungin

Study Results

Participant Flow

Arm/Group Title	Voriconazole Plus Caspofungin
Arm/Group Description	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 Caspofungin: 70 mg iv x 1 on day 1 (loading dose), followed by 50 mg iv daily on day 2 through day 84.
Period Title: Overall Study
STARTED	13
COMPLETED	10
NOT COMPLETED	3

Baseline Characteristics

Arm/Group Title	Voriconazole Plus Caspofungin
Arm/Group Description	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 Caspofungin: 70 mg iv x 1 on day 1 (loading dose), followed by 50 mg iv daily on day 2 through day 84.
Overall Participants	13
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	12 92.3%
>=65 years	1 7.7%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	45.916 (15.370)
Sex: Female, Male (Count of Participants)
Female	5 38.5%
Male	8 61.5%
Region of Enrollment (participants) [Number]
United States	13 100%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With a Complete or Partial Response Rate to the Combination of Voriconazole and Caspofungin at 12 Weeks.
Description	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.
Time Frame	12 weeks after starting treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Voriconazole Plus Caspofungin
Arm/Group Description	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 Caspofungin: 70 mg iv x 1 on day 1 (loading dose), followed by 50 mg iv daily on day 2 through day 84.
Measure Participants	13
Number [Participants]	4 30.8%

2. Secondary Outcome

Title	Duration of Survival up to 12 Weeks
Time Frame	up to 12 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

3. Secondary Outcome

Title	Safety
Time Frame	duration of study

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Arm/Group Title	Voriconazole Plus Caspofungin
Arm/Group Description	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 Caspofungin: 70 mg iv x 1 on day 1 (loading dose), followed by 50 mg iv daily on day 2 through day 84.
All Cause Mortality
	Voriconazole Plus Caspofungin
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Voriconazole Plus Caspofungin
	Affected / at Risk (%)	# Events
Total	10/13 (76.9%)
Blood and lymphatic system disorders
Sepsis	1/13 (7.7%)
Gastrointestinal disorders
Diarrhea	1/13 (7.7%)
Colitis	1/13 (7.7%)
General disorders
Abdominal Pain	2/13 (15.4%)
Disease Progression	2/13 (15.4%)
Psychiatric disorders
Altered Mental State	1/13 (7.7%)
Renal and urinary disorders
Liver and Renal failure	1/13 (7.7%)
Respiratory, thoracic and mediastinal disorders
Respiratory Distress	1/13 (7.7%)
Dyspnea	1/13 (7.7%)
Pulmonary Infection	1/13 (7.7%)
Vascular disorders
Cerebral Hemorrhage	1/13 (7.7%)
Intracerebral Hemorrhage	1/13 (7.7%)
Other (Not Including Serious) Adverse Events
	Voriconazole Plus Caspofungin
	Affected / at Risk (%)	# Events
Total	0/13 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.