- ICH GCP
- 미국 임상 시험 레지스트리
- 임상시험 NCT00086970
Ifosfamide With or Without O(6)-Benzylguanine in Treating Patients With Unresectable, Metastatic Solid Tumors
A Phase I Study Of BG In Combination With Ifosfamide For Advanced Solid Tumors
연구 개요
상세 설명
PRIMARY OBJECTIVES:
I. Determine the maximum tolerated dose of O6-benzylguanine when administered with standard high-dose ifosfamide in patients with unresectable, metastatic solid tumors.
II. Determine whether O6-benzylguanine enhances ifosfamide-mediated myelosuppression in patients treated with this regimen.
III. Determine the relationship between O6-benzylguanine dose and intra-individual variability in the degree of myelosuppression in patients treated with this regimen.
IV. Determine the safety and toxicity of this regimen in these patients.
SECONDARY OBJECTIVES:
I. Determine the effect of O6-benzylguanine on pharmacodynamic endpoints, including apoptosis and DNA damage, in patients treated with this regimen.
II. Determine the pharmacokinetics of O6-benzylguanine and its major metabolite, 8-oxoBG, in patients treated with this regimen.
OUTLINE: This is a randomized, open-label, multicenter, dose-escalation study of O6-benzylguanine.
Course 1: All patients receive high-dose ifosfamide IV continuously over 72 hours on days 1-3.
Course 2: Patients are randomized to 1 of 2 treatment arms.
Arm I: Patients receive high-dose ifosfamide as in course 1.
Arm II: Patients receive a bolus dose of O6-benzylguanine (BG) IV over 1 hour on day 1 followed by BG IV continuously and high-dose ifosfamide IV continuously over 72 hours on days 1-3. Cohorts of 6-12 patients receive escalating doses of BG (administered as a bolus and as a continuous infusion during course 2) until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 3 of 6 or 4 of 12 patients experience dose-limiting toxicity.
Course 3 and all subsequent courses: All patients receive BG (at the MTD determined in course 2, arm II) and high-dose ifosfamide as in course 2, arm II. In all courses, all patients also receive filgrastim (G-CSF) beginning on day 5 and continuing until blood counts recover. In all courses and in both arms, treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity.
연구 유형
등록 (실제)
단계
- 1단계
연락처 및 위치
연구 장소
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Illinois
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Chicago, Illinois, 미국, 60637-1470
- University of Chicago Comprehensive Cancer Center
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참여기준
자격 기준
공부할 수 있는 나이
건강한 자원 봉사자를 받아들입니다
연구 대상 성별
설명
Inclusion Criteria:
Histologically confirmed solid tumor
- Unresectable, metastatic disease
- No primary tumors
- Eligible for high-dose ifosfamide-based therapy
- No known brain metastases
- Performance status - ECOG 0-1
- Performance status - Karnofsky 70-100%
- More than 12 weeks
- Absolute neutrophil count ≥ 1,500/mm^3
- Platelet count ≥ 100,000/mm^3
- AST and ALT ≤ 2.5 times upper limit of normal
- Bilirubin normal
- Creatinine normal
- Creatinine clearance ≥ 60 mL/min
- No symptomatic congestive heart failure
- No unstable angina pectoris
- No cardiac arrhythmia
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception during and for 4 weeks after study participation
- No history of allergic reaction attributed to compounds of similar chemical or biological composition to O6-benzylguanine or other study agents
- No concurrent uncontrolled illness
- No active or ongoing infection
- No psychiatric illness or social situation that would preclude study compliance
- More than 24 hours since prior colony-stimulating factors (filgrastim [G-CSF] or sargramostim [GM-CSF])
- No prior hematopoietic stem cell transplantation
- No concurrent pegfilgrastim
- No concurrent immunotherapy
- More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered
- No other concurrent chemotherapy
- No concurrent hormonal therapy
- More than 4 weeks since prior radiotherapy and recovered
- No concurrent therapeutic radiotherapy
- More than 4 weeks since prior anticancer therapy
- No more than 2 prior cytotoxic regimens
- No concurrent combination antiretroviral therapy for HIV-positive patients
- No other concurrent anticancer agents or therapies
- No other concurrent investigational agents
공부 계획
연구는 어떻게 설계됩니까?
디자인 세부사항
- 주 목적: 치료
- 할당: 무작위
- 중재 모델: 병렬 할당
- 마스킹: 없음(오픈 라벨)
무기와 개입
참가자 그룹 / 팔 |
개입 / 치료 |
---|---|
실험적: Arm I (ifosfamide)
Patients receive high-dose ifosfamide IV continuously over 72 hours on days 1-3.
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주어진 IV
다른 이름들:
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실험적: Arm II (O6-benzylguanine, ifosfamide)
Patients receive a bolus dose of O6-benzylguanine (BG) IV over 1 hour on day 1 followed by BG IV continuously and high-dose ifosfamide IV continuously over 72 hours on days 1-3.
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주어진 IV
다른 이름들:
주어진 IV
다른 이름들:
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연구는 무엇을 측정합니까?
주요 결과 측정
결과 측정 |
측정값 설명 |
기간 |
---|---|---|
Change in degree of myelosuppression (thrombocytopenia and neutropenia) quantified by both duration of neutropenia and severity of neutropenia
기간: Baseline up to 1 year
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Baseline up to 1 year
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Maximum tolerated dose (MTD) of O6-benzylguanine defined as the dose preceding that at which 3 of 6 or 4 of 12 patients experience dose-limiting toxicity
기간: 21 days
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DLT is defined as any >= grade 3 non-hematologic toxicity, grade 4 thrombocytopenia, or prolonged neutropenia.
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21 days
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2차 결과 측정
결과 측정 |
측정값 설명 |
기간 |
---|---|---|
Pharmacodynamics including apoptosis and DNA damage
기간: Up to 1 year
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Up to 1 year
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Pharmacokinetics of O6-benzylguanine
기간: Up to day 3 of course 2
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Summarized using descriptive statistics (mean, median, standard deviation, and interquartile range).
Estimated via nonlinear regression.
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Up to day 3 of course 2
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공동 작업자 및 조사자
수사관
- 수석 연구원: Sonali Smith, University of Chicago Comprehensive Cancer Center
연구 기록 날짜
연구 주요 날짜
연구 시작
기본 완료 (실제)
연구 등록 날짜
최초 제출
QC 기준을 충족하는 최초 제출
처음 게시됨 (추정)
연구 기록 업데이트
마지막 업데이트 게시됨 (추정)
QC 기준을 충족하는 마지막 업데이트 제출
마지막으로 확인됨
추가 정보
이 연구와 관련된 용어
추가 관련 MeSH 약관
기타 연구 ID 번호
- NCI-2012-02601
- U01CA069852 (미국 NIH 보조금/계약)
- 12999B
- CDR0000371909 (레지스트리 식별자: PDQ (Physician Data Query))
이 정보는 변경 없이 clinicaltrials.gov 웹사이트에서 직접 가져온 것입니다. 귀하의 연구 세부 정보를 변경, 제거 또는 업데이트하도록 요청하는 경우 register@clinicaltrials.gov. 문의하십시오. 변경 사항이 clinicaltrials.gov에 구현되는 즉시 저희 웹사이트에도 자동으로 업데이트됩니다. .
이포스파마이드에 대한 임상 시험
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National Cancer Institute (NCI)완전한
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Memorial Sloan Kettering Cancer CenterColumbia University; Genentech, Inc.완전한
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M.D. Anderson Cancer CenterMerck Sharp & Dohme LLC완전한
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Italian Sarcoma GroupFrench Sarcoma Group; Grupo Espanol de Investigacion en Sarcomas모집하지 않고 적극적으로성인의 사지 및 몸통 벽의 국소 고위험 연조직 육종스페인, 이탈리아