- ICH GCP
- 미국 임상 시험 레지스트리
- 임상시험 NCT00909831
Hydroxychloroquine and Temsirolimus in Treating Patients With Metastatic Solid Tumors That Have Not Responded to Treatment
A Phase I Trial of Hydroxychloroquine in Combination With Temsirolimus in Patients With Refractory Solid Tumors
RATIONALE: Drugs used in chemotherapy, such as hydroxychloroquine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Temsirolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving hydroxychloroquine together with temsirolimus may kill more tumor cells.
PURPOSE: This phase I trial is studying the side effects and best dose of hydroxychloroquine when given together with temsirolimus in treating patients with metastatic solid tumors that have not responded to treatment.
연구 개요
상태
상세 설명
OBJECTIVES:
Primary
- Determine the maximum tolerated dose of hydroxychloroquine (HCQ) in combination with temsirolimus (TEM) in patients with metastatic refractory solid tumors.
Secondary
- Describe the toxicity of this regimen in these patients.
- Measure the response rate in patients treated with this regimen.
Tertiary
- Establish a population pharmacokinetic (PK) model for HCQ and its metabolites in combination with TEM.
- Use the population PK model to estimate the exposure of HCQ in individual patients.
- Compare PK parameters for this regimen to data from published single agent studies.
- Measure the change in median number of autophagic vesicles/cell in peripheral blood mononuclear cells with TEM alone and with TEM and HCQ and correlate these changes with HCQ exposure.
OUTLINE: This is a dose-escalation study of hydroxychloroquine.
Patients receive temsirolimus IV over 30 minutes once a week beginning in week 1 and oral hydroxychloroquine twice daily beginning in week 2. Courses repeat every 8 weeks in the absence of disease progression or unacceptable toxicity.
Blood samples are collected at baseline and periodically during study for pharmacokinetic and pharmacodynamic studies and measurement of autophagy inhibition. Samples are analyzed via HPLC and tandem mass spectrometry, immunoblotting assays, and electron microscopy.
연구 유형
등록 (예상)
단계
- 1단계
연락처 및 위치
연구 장소
-
-
Pennsylvania
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Philadelphia, Pennsylvania, 미국, 19104-4283
- Abramson Cancer Center of the University of Pennsylvania
-
-
참여기준
자격 기준
공부할 수 있는 나이
건강한 자원 봉사자를 받아들입니다
연구 대상 성별
설명
DISEASE CHARACTERISTICS:
Histologically confirmed refractory solid tumor for which no curative standard therapy exists
- Metastatic disease
Treated brain metastases that have been stable ≥ 3 months allowed
- At least 1 week since prior steroids
PATIENT CHARACTERISTICS:
- ECOG performance status of 0-1
- ANC ≥ 1,500/mm^3
- Platelet count ≥ 100,000/mm^3
- Creatinine ≤ 2 times upper limit of normal (ULN)
- ALT and AST ≤ 5 times ULN
- Total bilirubin ≤ 1.5 mg/dL
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- No serious concurrent infection or medical illness that would jeopardize the ability of the patient to receive the treatment outlined in this protocol with reasonable safety
No prior or other concurrent malignancy except for curatively treated carcinoma-in-situ at any site or basal cell carcinoma or squamous cell carcinoma of the skin
- Patients who have been free of disease (any prior malignancy) for ≥ 5 years are eligible
- No porphyria
- No psoriasis, except well controlled psoriasis under the care of a specialist
- No previously documented macular degeneration or diabetic retinopathy
- No HIV positivity
PRIOR CONCURRENT THERAPY:
- See Disease Characteristics
- Any number and type of prior anticancer therapies allowed
- No prior mTOR inhibitors
- At least 4 weeks since prior immunotherapy (i.e., aldesleukin, interferon, CTLA-4) or chemotherapy and recovered
- At least 2 weeks since prior oral targeted therapy and recovered
- At least 4 weeks since prior and no other concurrent investigational anticancer therapy (except for vaccines)
- No other concurrent therapy
- No concurrent combination antiretroviral therapy for HIV-positive patients
- No concurrent cytochrome P450 enzyme-inducing anticonvulsant drugs (i.e., phenytoin, carbamazepine, phenobarbital, primidone, or oxcarbazepine)
- Concurrent non-enzyme inducing anticonvulsants, including felbamate, valproic acid, gabapentin, lamotrigine, tiagabine, topiramate, zonisamide, or levetiracetam allowed
- Concurrent hematologic growth factors (filgrastim [G-CSF], pegfilgrastim, epoetin alfa) allowed in patients with severe myelosuppression
공부 계획
연구는 어떻게 설계됩니까?
디자인 세부사항
- 주 목적: 치료
연구는 무엇을 측정합니까?
주요 결과 측정
결과 측정 |
|---|
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Maximum tolerated dose of hydroxychloroquine
|
2차 결과 측정
결과 측정 |
|---|
|
응답률
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Toxicity rate as assessed by NCI CTCAE v. 3.0
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Pharmacokinetic and pharmacodynamic correlative endpoints
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공동 작업자 및 조사자
수사관
- 수석 연구원: Ravi Amaravadi, MD, Abramson Cancer Center of the University of Pennsylvania
연구 기록 날짜
연구 주요 날짜
연구 시작
기본 완료 (실제)
연구 완료 (실제)
연구 등록 날짜
최초 제출
QC 기준을 충족하는 최초 제출
처음 게시됨 (추정)
연구 기록 업데이트
마지막 업데이트 게시됨 (실제)
QC 기준을 충족하는 마지막 업데이트 제출
마지막으로 확인됨
추가 정보
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. .
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