Caspofungin Maximum Tolerated Dose in Patients With Invasive Aspergillosis
A Phase II Dose Escalation Study of Caspofungin in Patients With Invasive Aspergillosis
연구 개요
상세 설명
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.
연구 유형
등록 (실제)
단계
- 2 단계
연락처 및 위치
참여기준
자격 기준
공부할 수 있는 나이
건강한 자원 봉사자를 받아들입니다
연구 대상 성별
설명
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.
공부 계획
연구는 어떻게 설계됩니까?
디자인 세부사항
- 주 목적: 치료
- 할당: 무작위화되지 않음
- 중재 모델: 병렬 할당
- 마스킹: 없음(오픈 라벨)
무기와 개입
참가자 그룹 / 팔 |
개입 / 치료 |
|---|---|
|
실험적: 1st cohort
70mg caspofungin 1x/day
|
i.v.
다른 이름들:
|
|
실험적: 2nd cohort
100mg caspofungin 1x/day
|
i.v.
다른 이름들:
|
|
실험적: 3rd cohort
150mg caspofungin 1x/day
|
i.v.
다른 이름들:
|
|
실험적: 4th cohort
200mg caspofungin 1x/day
|
i.v.
다른 이름들:
|
연구는 무엇을 측정합니까?
주요 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
|
Safety and Tolerability of Caspofungin in Four Escalating Dosages in Adult Patients With Hematologic Malignancies and Proven or Probable Invasive Aspergillosis
기간: 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.
|
End of caspofungin treatment, treatment duration varied between 3 and 29 days (mean: 20.5; median: 24.5)
|
2차 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
|
Efficacy of Caspofungin in Four Escalating Dosages in the Treatment of Proven or Probable Invasive Aspergillosis.
기간: 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. |
End of caspofungin treatment; 4 weeks follow-up; 12 weeks follow-up
|
공동 작업자 및 조사자
수사관
- 수석 연구원: Oliver A. Cornely, MD, Klinikum der Universität zu Köln
간행물 및 유용한 링크
일반 간행물
- Cornely OA, Vehreschild JJ, Vehreschild MJ, Wurthwein G, Arenz D, Schwartz S, Heussel CP, Silling G, Mahne M, Franklin J, Harnischmacher U, Wilkens A, Farowski F, Karthaus M, Lehrnbecher T, Ullmann AJ, Hallek M, Groll AH. Phase II dose escalation study of caspofungin for invasive Aspergillosis. Antimicrob Agents Chemother. 2011 Dec;55(12):5798-803. doi: 10.1128/AAC.05134-11. Epub 2011 Sep 12.
- Wurthwein G, Cornely OA, Trame MN, Vehreschild JJ, Vehreschild MJ, Farowski F, Muller C, Boos J, Hempel G, Hallek M, Groll AH. Population pharmacokinetics of escalating doses of caspofungin in a phase II study of patients with invasive aspergillosis. Antimicrob Agents Chemother. 2013 Apr;57(4):1664-71. doi: 10.1128/AAC.01912-12. Epub 2013 Jan 18.
연구 기록 날짜
연구 주요 날짜
연구 시작
기본 완료 (실제)
연구 완료 (실제)
연구 등록 날짜
최초 제출
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처음 게시됨 (추정)
연구 기록 업데이트
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추가 정보
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