STA-9090(Ganetespib) in Patients With Unresectable Stage III or Stage IV Melanoma
2017년 3월 1일 업데이트: F. Stephen Hodi, MD, Dana-Farber Cancer Institute
This Trial is an Open Label, Parallel Cohort, Phase II Study Evaluating the Efficacy of the Heat Shock Protein 90 (Hsp90) Inhibitor STA-9090 in Patients With Unresectable Stage III or Stage IV Melanoma Who Were Intolerant of, or Progressed on, Prior Tyrosine Kinase Inhibitor Treatment. Two Cohorts Will Enroll Concurrently. One Cohort Will be Composed of Patients With Melanoma Expressing a Mutation in the Protein BRAF and the Other Cohort Will be Composed of Patients With Melanoma Expressing Wild-type BRAF.
STA9090 is a drug which inactivates or blocks the work of a protein called Heat Shock Protein 90 or HSP90.
HSP90 is a protein that helps some molecules inside your cells to have the right shape.
By stopping HSP90's activity, those molecules never get to have the right structure of be functional and they are destroyed.
The investigators believe that if they stop the activity of HSP90, the rapidly dividing cells that are in your tumor(s) may slow down.
In this research study the investigators are looking to see how well STA9090 works in stopping the spread of your melanoma.
연구 개요
상세 설명
OBJECTIVES:
Primary
- To determine the proportion of patients alive, free of disease progression, and still taking STA-9090 at 6 months by BRAF mutant or wild type (WT) status.
Secondary
- To assess best overall response rate and six month response rate by BRAF status
- To evaluate the rates of one-year overall survival and progression-free survival by BRAF status
- To determine safety and tolerability of STA-9090 by BRAF status
Exploratory
- To compare the rates of response and of six-month PFS between BRAF status cohorts
- To explore, using peripheral blood mononuclear cells, the relationship between change in expression of hsp90 client proteins (e.g., BRAF, CRAF, AKT, CDK4, KIT) with response to therapy and progression free survival by BRAF status
- To explore the relationship in biopsied melanoma metastases between changes in expression of hsp90 client proteins (e.g., BRAF, CRAF, AKT, CDK4, KIT) with response to therapy and progression-free survival
- To explore response rate and 6 month progression free survival, in subset of patients with melanoma expressing a mutation in KIT
연구 유형
중재적
등록 (실제)
3
단계
- 2 단계
연락처 및 위치
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연구 장소
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Massachusetts
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Boston, Massachusetts, 미국, 02215
- Dana-Farber Cancer Institute
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참여기준
연구원은 적격성 기준이라는 특정 설명에 맞는 사람을 찾습니다. 이러한 기준의 몇 가지 예는 개인의 일반적인 건강 상태 또는 이전 치료입니다.
자격 기준
공부할 수 있는 나이
18년 이상 (성인, 고령자)
건강한 자원 봉사자를 받아들입니다
아니
연구 대상 성별
모두
설명
- Histologically confirmed unresectable stage III or stage IV melanoma
- Treatment of unresectable stage III or stage IV melanoma with a tyrosine kinase inhibitor within prior 4 months. Sorafenib for purposes of eligibility will not be considered acceptable prior therapy
- Sufficient tumor available to determine if expresses wild-type or mutated BRAF if result not already known. The presence or absence of BRAF mutation needs to be determined at BWH, MGH, BIDMC, by Drs. Christopher Corless and Michael Heinrich at Cancer Pathology Shared Resource Oregon Health & Science University, or in context of eligibility assessment after signing consent to a previous clinical trial
- Sufficient tumor available to determine if expresses a mutation KIT
- Agreement to allow tumor to be evaluated for mutations in KIT and BRAF
- ECOG performance status ≤ 1
- Life expectancy of ≥ 6 months
- Age ≥ 18 years
- WBC ≥ 3 x 103/ul
- ANC ≥ 1,500/ul
- Platelets ≥ 100 x 103/ul
- Hemoglobin ≥ 9 gm/dl
- Serum creatinine ≤ 1.5 x ULN
- Calculated creatinine clearance ≥ 60 mL/min
- AST ≤ 2.5 x ULN; -OR- AST ≤ 5 x ULN in the presence of known liver metastases
- ALT ≤ 2.5 x ULN; -OR- ALT ≤ 5 x ULN in the presence of known liver metastases
- Total bilirubin ≤ 1.5 x ULN
- Potassium within normal range or correctable with supplements
- Magnesium within normal range or correctable with supplements
- Corrected serum calcium within normal range, or correctable with supplements
- Not pregnant or breastfeeding. Female subjects of childbearing age must have a negative serumpregnancy test at study entry
- Women of childbearing potential and men must agree to use adequate contraception prior to study entry and for the duration of study participation and for 6 months following last study drug administration
- Agreement to provide blood samples for pharmacodynamic studies utilizing Peripheral Blood Mononuclear Cells (PMBCs) as outlined in protocol
- At least one site of measurable disease as defined by at least 1 cm in greatest dimension. This site must be different from the sites to be used for biopsy. No prior radiation therapy or directed ablation to the site of measureable disease
- Able to understand and willing to sign a written informed consent document
- Willing and able to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures
- No chemotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to study entry
- No radiotherapy within 4 weeks prior to study entry
- Subject has recovered from adverse events due to agents administered more than 4 weeks earlier
- No tyrosine kinase inhibitor within 14 days prior to study entry
- No major surgery within 4 weeks prior to first dose of STA-9090
- No minor surgery within 7 days of first dose of STA-9090
- No history of or current coronary artery disease, myocardial infarction, angina pectoris, angioplasty
- or coronary bypass surgery
- No current treatment with the following antiarrythmic drugs: flecainide, moricizine or propafenone
- No NYHA class II/III/IV congestive heart failure with a history of dyspnea, orthopnea, or edema that requires current treatment with angiotensin convering enzyme inhibitors, angiotensin II receptor blockers, beta-blockers, or diuretics
- No current or prior radiation to the left hemithorax
- No embolization procedure or ablation procedure to treat tumor within 4 weeks of first dose of STA- 9090
- Not receiving any other investigational agents
- No poor venous access for study drug administration unless subject can use silicone based catheters
- No history of brain metastases or of leptomeningeal involvement
- No history of severe allergic reactions or hypersensitivity reactions attributed to compounds of similar chemical or biologic composition to STA-9090 (e.g. olyethylene glycol [PEG] 300 or Polysorbate 80)
- Baseline QTc ≤ 470 msec
- No previous history of QT prolongation while taking other medications
- Ventricular ejection fraction (EF) > 55%
- No treatment with chronic immunosuppressants
- No melanoma of ocular primary
- No prior treatment with hsp90 inhibitor
- No uncontrolled intercurrent illness including, but not limited to ongoing or active infection, ventricular arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
- No other medications, or severe acute/chronic medical of psychiatric conditions or laboratory abnormality that may increase the risk associated with the study participation or study drug administration, or may interfere with the interpretation of study results, and in the judgment of the investigator would make the subject inappropriate for entry into the study
- No history of a different malignancy except for the following circumstances. Individuals with a history of other malignancies are eligible if they have been disease-free for at least 5 years and are deemed by the investigator to be at low risk for recurrence of that malignancy. Individuals with the following cancers are eligible if diagnosed and treated within the past 5 years: cervical cancer in situ, and basal cell or squamous cell carcinoma of the skin
- No HIV-positive subject on combination antiretroviral therapy
- No more than 3 prior systemic therapies for unresectable stage III or stage IV melanoma
- No concomitant use of medications associated with a high incidence of QT prolongation as outlined
공부 계획
이 섹션에서는 연구 설계 방법과 연구가 측정하는 내용을 포함하여 연구 계획에 대한 세부 정보를 제공합니다.
연구는 어떻게 설계됩니까?
디자인 세부사항
- 주 목적: 치료
- 할당: 무작위화되지 않음
- 중재 모델: 단일 그룹 할당
- 마스킹: 없음(오픈 라벨)
무기와 개입
참가자 그룹 / 팔 |
개입 / 치료 |
|---|---|
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실험적: STA-9090 Cohort A
Patients enrolled into two possible cohorts based on tumor expression of BRAF: Cohort A - BRAF mutant disease or Cohort B - BRAF wild type.
Cohort A patients received STA-9090 200 mg/m2 once weekly (d1, 8, 15 of 28 day cycle).
Patients were treated until evidence of disease progression, unacceptable toxicity, intercurrent illness or withdrawal.
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다른 이름들:
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실험적: STA-9090 Cohort B
Patients enrolled into two possible cohorts based on tumor expression of BRAF: Cohort A - BRAF mutant disease or Cohort B - BRAF wild type.
Cohort B patients received STA-9090 150 mg/m2 twice weekly (d1, 4, 8, 11, 15, 18 of 28 day cycle).
Patients were treated until evidence of disease progression, unacceptable toxicity, intercurrent illness or withdrawal.
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다른 이름들:
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연구는 무엇을 측정합니까?
주요 결과 측정
결과 측정 |
측정값 설명 |
기간 |
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6-month Progression-Free Survival Rate
기간: Disease was evaluated radiologically at baseline and every 8 weeks on treatment; Treatment continued until evidence of disease progression or unacceptable toxicity. Relevant for this endpoint was disease status at 6 months.
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6-month progression-free survival rate was defined as the proportion of patients absent death or progression based on Response Evaluation Criteria In Solid Tumors Criteria (RECIST) before 6 months.
Per RECIST 1.0 criteria: progressive disease (PD) is at least a 20% increase in the sum of longest diameter (LD) of target lesions taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.
PD for the evaluation of non-target lesions is the appearance of one or more new lesions and/or unequivocal progression of non-target lesions.
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Disease was evaluated radiologically at baseline and every 8 weeks on treatment; Treatment continued until evidence of disease progression or unacceptable toxicity. Relevant for this endpoint was disease status at 6 months.
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2차 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
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Best Overall Response
기간: Disease was evaluated radiologically at baseline and every 8 weeks on treatment. Median (range) treatment duration was 1 cycle/4 weeks (1-2 cycles; 4-8 weeks).
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Best overall response (BOR) on treatment was based on RECIST 1.0 criteria.
For target lesions, complete response (CR) is complete disappearance of all target lesions and partial response (PR) is at least a 30% decrease in the sum of longest diameter (LD) of target lesions, taking as reference baseline sum LD.
CR or PR confirmation required within 4 weeks.
Progressive disease (PD) is at least a 20% increase in the sum LD of target lesions from smallest sum LD as reference or the appearance of one or more new lesions.
Stable disease (SD) is neither meeting PR or PD.
PD for the evaluation of non-target lesions is the appearance of one or more new lesions and/or unequivocal progression of non-target lesions.
CR is disappearance of all non-target lesions.
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Disease was evaluated radiologically at baseline and every 8 weeks on treatment. Median (range) treatment duration was 1 cycle/4 weeks (1-2 cycles; 4-8 weeks).
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Overall Survival
기간: Patients were followed every 4 weeks for survival until death, lost to follow-up or study closure (approximately 6 months after the last patient ended treatment). In this study cohort, patients were followed up to 13 weeks.
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Overall survival is defined as the time from study entry to death or date last known alive and estimated using Kaplan-Meier (KM) methods.
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Patients were followed every 4 weeks for survival until death, lost to follow-up or study closure (approximately 6 months after the last patient ended treatment). In this study cohort, patients were followed up to 13 weeks.
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여기에서 이 연구와 관련된 사람과 조직을 찾을 수 있습니다.
수사관
- 수석 연구원: F. Stephen Hodi, M.D., Dana-Farber Cancer Institute
연구 기록 날짜
이 날짜는 ClinicalTrials.gov에 대한 연구 기록 및 요약 결과 제출의 진행 상황을 추적합니다. 연구 기록 및 보고된 결과는 공개 웹사이트에 게시되기 전에 특정 품질 관리 기준을 충족하는지 확인하기 위해 국립 의학 도서관(NLM)에서 검토합니다.
연구 주요 날짜
연구 시작
2011년 9월 1일
기본 완료 (실제)
2012년 9월 1일
연구 완료 (실제)
2012년 9월 1일
연구 등록 날짜
최초 제출
2011년 4월 29일
QC 기준을 충족하는 최초 제출
2012년 3월 8일
처음 게시됨 (추정)
2012년 3월 13일
연구 기록 업데이트
마지막 업데이트 게시됨 (실제)
2017년 4월 12일
QC 기준을 충족하는 마지막 업데이트 제출
2017년 3월 1일
마지막으로 확인됨
2017년 1월 1일
추가 정보
이 연구와 관련된 용어
추가 관련 MeSH 약관
기타 연구 ID 번호
- 11-039
개별 참가자 데이터(IPD) 계획
개별 참가자 데이터(IPD)를 공유할 계획입니까?
아니
약물 및 장치 정보, 연구 문서
미국 FDA 규제 의약품 연구
예
미국 FDA 규제 기기 제품 연구
아니
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. .