Temsirolimus and Valproic Acid in Treating Young Patients With Relapsed Neuroblastoma, Bone Sarcoma, or Soft Tissue Sarcoma
A Multi-center Phase I Trial of Temsirolimus in Combination With Valproic Acid in Children and Adolescents With Multiply Relapsed Pediatric Solid Tumors
RATIONALE: Drugs such as temsirolimus and valproic acid may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Valproic acid may also stop the growth of solid tumors by blocking blood flow to the tumor.
PURPOSE: This phase I trial is studying the side effects and the best dose of temsirolimus when given together with valproic acid in treating young patients with relapsed neuroblastoma, bone sarcoma, or soft tissue sarcoma.
연구 개요
상태
개입 / 치료
상세 설명
OBJECTIVES:
Primary
- To identify the maximum-tolerated dose of temsirolimus in combination with valproic acid in highly pretreated pediatric patients with refractory solid tumors.
Secondary
- To estimate the objective response rate in patients treated with this regimen.
- To estimate the progression-free survival of patients treated with this regimen.
- To explore the association between tumor IGF-IR, mTOR expression, HDAC, autophagy biomarkers, and sera levels of temsirolimus, valproate, and VEGF-A with toxicity and disease response.
- To evaluate the ability of selected member divisions of a newly developed North Carolina-based pediatric oncology consortium to cooperate in clinical trials.
OUTLINE: This a multicenter, dose-escalation study of temsirolimus.
Patients receive temsirolimus IV over 30-60 minutes on days 1, 8, 15, and 22 and oral valproic acid* 3 times daily on days 1-28. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.
Blood samples are collected at baseline and periodically during study for pharmacokinetic and VEGF-A studies. Tumor tissue samples from archived biopsy are also analyzed for IGF-IR, mTOR expression, HDAC, and autophagy biomarkers.
After completion of study therapy, patients are followed every 3 months for 1 year, every 4 months for 2 years, and then every 6 months for 2 years.
NOTE: * Doses of valproic acid are titrated beginning 3-7 days prior to starting temsirolimus to achieve plasma levels of 75-100 µg/mL.
연구 유형
등록 (실제)
단계
- 1단계
연락처 및 위치
연구 장소
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North Carolina
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Chapel Hill, North Carolina, 미국, 27599-7295
- Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill
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Charlotte, North Carolina, 미국
- Carolina Healthcare System
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참여기준
자격 기준
공부할 수 있는 나이
건강한 자원 봉사자를 받아들입니다
연구 대상 성별
설명
DISEASE CHARACTERISTICS:
Histologically confirmed malignant solid tumor at original diagnosis, including the following:
- Neuroblastoma
- Bone sarcomas (primary neuroectodermal tumors/ Ewing sarcoma (PNET/ES), osteosarcoma)
- Soft tissue sarcomas (rhabdosarcoma and related tumors)
- Histologically confirmed of relapsed disease is highly recommended but not mandatory
- Measurable disease according to RECIST
Refractory or progressive disease after ≥ 1 and ≤ 4 prior chemotherapy regimens
- Patients with neuroblastoma, PNET/ES, or rhabdosarcoma must have failed a cyclophosphamide/topotecan-containing regimen
- Stem cell transplantation, including preparative regimen and post-transplant immunotherapy, is considered to be 1 regimen
PATIENT CHARACTERISTICS:
- Karnofsky performance status (PS) 50-100% (or Lansky PS 50-100%)
- Life expectancy ≥ 8 weeks
- ANC ≥ 750/mm^3
- Platelet count ≥ 75,000/mm^3 (transfusion independent)
Hemoglobin 8.0 g/dL (may receive RBC transfusions)
- Patients with tumor metastatic to bone marrow are allowed to receive transfusions to maintain hemoglobin and platelet counts
- Serum creatinine normal
- Total bilirubin ≤ 1.5 times upper limit of normal (ULN) OR direct bilirubin < 1.0 mg/dL (if total bilirubin > 2.0 mg/dL)
- ALT < 5 times ULN
- Negative pregnancy test
- Not pregnant or nursing
- Fertile patients must use effective contraception
- Families must be able to give consent in English or Spanish
- No allergy to H1 antihistamines
PRIOR CONCURRENT THERAPY:
- See Disease Characteristics
- More than 2 weeks since prior chemotherapy, immunotherapy, or radiotherapy and recovered
- No concurrent anticonvulsants, including valproic acid
- No concurrent strong inducers or inhibitors of CYP3A4, including grapefruit juice
공부 계획
연구는 어떻게 설계됩니까?
디자인 세부사항
- 주 목적: 치료
- 할당: 해당 없음
- 중재 모델: 단일 그룹 할당
- 마스킹: 없음(오픈 라벨)
무기와 개입
참가자 그룹 / 팔 |
개입 / 치료 |
|---|---|
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다른: Single Arm Temsirolimus + Valproic Acid
Drug: temsirolimus 60-230mg/m2 weekly during each 28 day course, for up to 12 courses Drug: valproic acid (VPA) All patients will be given oral VPA (5 mg/kg, 3 times a day for each 28 day course, up to 12 courses |
60-230mg/m2 weekly during each 28 day course, for up to 12 courses
다른 이름들:
All patients will be given oral VPA (5 mg/kg, 3 times a day for each 28 day course, up to 12 courses
다른 이름들:
|
연구는 무엇을 측정합니까?
주요 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
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Maximum tolerated dose (MTD) of temsirolimus in combination with valproic acid
기간: 4 weeks
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The planned starting dose of Temsirolimus is 60mg/M2.
The traditional 3+3 design will be used, where the MTD is defined as the dose with the probability of a DLT of 0.20
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4 weeks
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2차 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
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Objective response rate
기간: every 12 weeks
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Each patient will be classified according to their "best response".
Best response is determined from the sequence of the objective statuses as described in RECIST 1.1
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every 12 weeks
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Progression-free survival
기간: 3 years
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If the patient's disease has not progressed at the time protocol-directed therapy is complete, any tumor assessments available during the follow-up period (up to 3 years) will be evaluated using RECSIT 1.1
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3 years
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Temsirolimus pharmakokinetic parameters (Maximum plasma concentration)
기간: doses 1 and 5
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Blood will be drawn prior to, 30 minutes, 1hr, 2hr, 5hr, 24hr after completion of doses 1 and 5. Levels of Temsirolimus will be measured using validated liquid chromatography and tandem mass spectroscopic methods
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doses 1 and 5
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공동 작업자 및 조사자
수사관
- 수석 연구원: Julie Blatt, MD, UNC Lineberger Comprehensive Cancer Center
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 (추정)
QC 기준을 충족하는 마지막 업데이트 제출
마지막으로 확인됨
추가 정보
이 연구와 관련된 용어
키워드
추가 관련 MeSH 약관
- 신경계 질환
- 신생물, 결합 및 연조직
- 조직학적 유형에 따른 신생물
- 부위별 신생물
- 신생물, 선상 및 상피
- 신생물, 신경상피
- 신경외배엽 종양
- 신생물, 생식 세포 및 배아
- 신생물, 신경 조직
- 신경외배엽 종양, 원시
- 신경외배엽 종양, 원시, 말초
- 신생물
- 육종
- 신경계 신생물
- 중추신경계 신생물
- 신경 모세포종
- 약물의 생리적 효과
- 신경 전달 물질
- 약리작용의 분자기전
- 항감염제
- 중추신경계 억제제
- 효소 억제제
- 항종양제
- 면역억제제
- 면역학적 요인
- 항균제
- 안정제
- 향정신성 약물
- GABA 에이전트
- 항경련제
- 항조증제
- 항생제, 항종양제
- 항진균제
- 발프로산
- 시롤리무스
기타 연구 ID 번호
- LCCC 0901
- P30CA016086 (미국 NIH 보조금/계약)
- CDR0000665319 (기타 식별자: PDQ)
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. .
Temsirolimus에 대한 임상 시험
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