A Study of Vemurafenib in Previously Treated Patients With Metastatic Melanoma
2017년 6월 26일 업데이트: Hoffmann-La Roche
An Open-label Multicenter Study on the Efficacy of Continuous Oral Dosing of Vemurafenib on Tumour Response in Previously Treated Patients With Metastatic Melanoma
This open-label single arm study will assess the efficacy, safety and tolerability of Vemurafenib in previously treated patients with metastatic melanoma.
Patients will receive oral Vemurafenib [RG7204; PLEXXIKON: PLX4032] at a dose of 960 mg b.i.d.
continuously until disease progression or withdrawal from study and will be assessed at regular intervals for tumour response and tolerability.
Target sample size is <100 patients.
연구 개요
연구 유형
중재적
등록 (실제)
132
단계
- 2 단계
연락처 및 위치
이 섹션에서는 연구를 수행하는 사람들의 연락처 정보와 이 연구가 수행되는 장소에 대한 정보를 제공합니다.
연구 장소
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California
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Los Angeles, California, 미국, 90095-6984
- UCLA - School of Medicine; Division of Hematology/Oncology
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Colorado
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Denver, Colorado, 미국, 80262
- University of Colorado
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Florida
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Tampa, Florida, 미국, 33612
- Moffitt Cancer Center
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Massachusetts
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Boston, Massachusetts, 미국, 02215
- Beth Israel Deaconess Medical Center
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Boston, Massachusetts, 미국, 02115
- Dana Farber Cancer Inst. ; Dept. of Medical Oncology
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Boston, Massachusetts, 미국, 02114
- Massachusetts General Hospital;Hematology/ Oncology
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New York
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New York, New York, 미국, 10036
- New York University Medical Center
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Pennsylvania
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Philadelphia, Pennsylvania, 미국, 19104-4283
- Hospital of the Uni of Pennsylvania; Section of Hematology/Oncology
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Pittsburgh, Pennsylvania, 미국, 15213
- University of Pittsburgh
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Tennessee
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Nashville, Tennessee, 미국, 37232
- Vanderbilt-Ingram Cancer Ctr
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Texas
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Dallas, Texas, 미국, 75246
- Texas Oncology-Baylor Sammons Cancer Center
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Houston, Texas, 미국, 77030
- University of Texas M.D. Anderson Cancer Center
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New South Wales
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Newcastle, New South Wales, 호주, 2298
- Calvary Mater Newcastle; Melanoma Clinic
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Westmead, New South Wales, 호주, 2145
- Westmead Hospital; Medical Oncology and Pallative Care
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Victoria
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Melbourne, Victoria, 호주, 3000
- Peter Maccallum Cancer Institute; Medical Oncology
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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
Inclusion Criteria:
- adult patients >/=18 years of age
- histologically confirmed metastatic melanoma (Stage IV, AJCC)
- patients must have completed and failed at least one prior standard of care regimen (e.g. DTIC, temozolomide, etc.)
- BRAF V600E positive mutation (by Roche CoDx BRAF mutation assay)
- measurable disease by RECIST criteria
- negative pregnancy test and, for fertile men and women, effective contraception during treatment and for 6 months after completion
Exclusion Criteria:
- active CNS metastases on CT/MRI within 28 days prior to enrollment
- history of or known carcinomatous meningitis
- previous treatment with BRAF (sorafenib allowed) or MEK inhibitor
- cardiac dysrhythmias >2 NCI CTCAE or treatment with drugs with dysrhythmic potential
- uncontrolled hypertension(>150/100mmHg) despite optimal medical therapy
- infectious disease including HIV, HBV and HCV
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: 해당 없음
- 중재 모델: 단일 그룹 할당
- 마스킹: 없음(오픈 라벨)
무기와 개입
참가자 그룹 / 팔 |
개입 / 치료 |
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실험적: 단일 암
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960 mg b.i.d.
continuous oral dosing
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연구는 무엇을 측정합니까?
주요 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
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Best Overall Response (BOR) Assessed by an Independent Review Committee Using Response Evaluation Criteria In Solid Tumors (RECIST 1.1)
기간: From first treatment through September 27, 2010
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BOR was defined as a complete response (CR) or partial response (PR) confirmed per Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1.
Patients who never received study treatment and treated patients without any post-baseline tumor assessments were considered as non-responders.
CR: Disappearance of all target lesions, all non-target lesions, and no new lesion.
Any pathological lymph nodes must have had reduction in the short axis to <10 mm.
PR: At least a 30% decrease in the sum of diameters of target lesions, no progression in non-target lesion, and no new lesion.
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From first treatment through September 27, 2010
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2차 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
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Best Overall Response (BOR) Assessed by the Investigator Using Response Evaluation Criteria In Solid Tumors (RECIST 1.1)
기간: From first treatment through September 27, 2010
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BOR was defined as a complete response (CR) or partial response (PR) confirmed per Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1.
Patients who never received study treatment and treated patients without any post-baseline tumor assessments were considered as non-responders.
CR: Disappearance of all target lesions, all non-target lesions, and no new lesion.
Any pathological lymph nodes must have had reduction in the short axis to <10 mm.
PR: At least a 30% decrease in the sum of diameters of target lesions, no progression in non-target lesion, and no new lesion.
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From first treatment through September 27, 2010
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Duration of Response Assessed by an Independent Review Committee Using Response Evaluation Criteria In Solid Tumors (RECIST 1.1)
기간: From first treatment through September 27, 2010
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Duration of response was defined as the time interval between the date of the earliest qualifying response and the date of disease progression (PD) or death, only for those patients whose best overall response was complete response or partial response.
PD: At least 20% increase in the sum of diameters of target lesions compared to Nadir (smallest sum of diameters on-study), unequivocal progression of existing non-target lesions, or presence of new lesion.
For patients who were alive without progression, duration of response was censored on the date of the last evaluable tumor assessment.
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From first treatment through September 27, 2010
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Time to Response Assessed by an Independent Review Committee Using Response Evaluation Criteria In Solid Tumors (RECIST 1.1)
기간: From first treatment through September 27, 2010
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Time to response was defined as the interval between the date of the first treatment and the date of the first documentation of confirmed complete response (CR) or partial response (PR), whichever occurred first.
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From first treatment through September 27, 2010
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Progression Free Survival (PFS) Assessed by an Independent Review Committee Using Response Evaluation Criteria In Solid Tumors (RECIST 1.1)
기간: From first treatment through September 27, 2010
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PFS was defined the time interval between the date of the first treatment and the date of progression or death from any cause, whichever occurred first.
Deaths that occurred in patients without disease progression were considered to be a PFS event on the date of death.
Patients who neither progressed nor died were censored on the date of the last evaluable tumor assessment prior to the data cutoff date.
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From first treatment through September 27, 2010
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Overall Survival
기간: From first treatment through September 27, 2010
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Overall survival was defined as the time from the date of the first treatment to the date of death, regardless of the cause of death.
For patients who were alive at the time of analysis, overall survival was censored at the last date the patient was known to be alive prior to the data cutoff date.
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From first treatment through September 27, 2010
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Improvement in Physical Symptoms (Improvement in Physician's Assessment of Global Performance Status and Oxygen Saturation Requirements, and Decrease in Total Dose and Frequency of Narcotic Pain Analgesics) During Treatment in Comparison to Baseline
기간: From first treatment through September 27, 2010
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Three parameters were measured.
(1) Improvement in the Physician's Assessment of Global Performance status on a 7-point scale (1=very much better to 7=very much worse).
(2) Improvement in oxygen saturation requirements, defined as a clinically meaningful increase in oxygen saturation requirement (from a baseline value < 95% to ≥ 95% saturation using a pulse oximeter).
(3) A decrease in total dose and frequency of narcotic pain analgesics.
The percentage of patients showing improvement (1 and 2) or a decrease (3) are reported.
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From first treatment through September 27, 2010
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Maximum Plasma Concentration (Cmax) of Vemurafenib on Day 15 of Cycle 1
기간: Pre-dose to 8 hours post-dose on Day 15 of Cycle 1
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Blood samples for assessing the concentration of vemurafenib in plasma were drawn before the morning dose and at 2, 4, 6, and 8 hours post-dose on Day 15 of Cycle 1. Pharmacokinetic parameters were estimated by non-compartmental analysis (Win Non-Lin).
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Pre-dose to 8 hours post-dose on Day 15 of Cycle 1
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Vemurafenib Plasma Level Area Under the Curve From 0 to 8 Hours (AUC0-8h) on Day 15 of Cycle 1
기간: Pre-dose to 8 hours post-dose on Day 15 of Cycle 1
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Blood samples for assessing the concentration of vemurafenib in plasma were drawn before the morning dose and at 2, 4, 6, and 8 hours post-dose on Day 15 of Cycle 1. Pharmacokinetic parameters were estimated by non-compartmental analysis (Win Non-Lin).
AUC0-8h was calculated using the linear trapezoidal rule.
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Pre-dose to 8 hours post-dose on Day 15 of Cycle 1
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Vemurafenib Plasma Levels at Various Treatment Cycles
기간: Pre-dose Cycle 1 Day 1 to 4 hours post-dose Cycle 10 Day 1
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Blood samples for assessing the concentration of vemurafenib in plasma were drawn before the morning dose and 4 hours post-dose at Day 1 of Cycles 1, 2, 3, 4, 6, 8, and 10.
Each Cycle was 3 weeks in duration.
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Pre-dose Cycle 1 Day 1 to 4 hours post-dose Cycle 10 Day 1
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Time-matched Change From Baseline in the Study Specific Corrected QT Interval (QTcP)
기간: Pre-dose Cycle 1 Day 1 to pre-dose Cycle 6 Day 1
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Three electrocardiograms (ECG) were obtained pre-dose and 2, 4, 6, and 8 hours post-dose at Days 1 and 15 of Cycle 1 and again pre-dose and 4 hours post-dose at various Cycles throughout treatment.
Five baseline triplicate ECGs were obtained before the start of treatment at the same time points used during treatment.
Reported is the largest mean time-matched QTcP change from baseline.
QTcP=QT/(60/heart rate)^β (β=mean [calculated separately for males and females] log-transformed QT versus log-transformed RR regression slopes using all available pre-treatment (baseline) ECG values.
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Pre-dose Cycle 1 Day 1 to pre-dose Cycle 6 Day 1
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Percentage of Patients With Adverse Event
기간: From first treatment through September 27, 2010
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The intensity of adverse events was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events v 4.0 (CTCAE) on a 5-point scale (Grade 1 to 5: Mild, Moderate, Severe, Life-threatening, and Death).
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From first treatment through September 27, 2010
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공동 작업자 및 조사자
여기에서 이 연구와 관련된 사람과 조직을 찾을 수 있습니다.
간행물 및 유용한 링크
연구에 대한 정보 입력을 담당하는 사람이 자발적으로 이러한 간행물을 제공합니다. 이것은 연구와 관련된 모든 것에 관한 것일 수 있습니다.
일반 간행물
- Su F, Viros A, Milagre C, Trunzer K, Bollag G, Spleiss O, Reis-Filho JS, Kong X, Koya RC, Flaherty KT, Chapman PB, Kim MJ, Hayward R, Martin M, Yang H, Wang Q, Hilton H, Hang JS, Noe J, Lambros M, Geyer F, Dhomen N, Niculescu-Duvaz I, Zambon A, Niculescu-Duvaz D, Preece N, Robert L, Otte NJ, Mok S, Kee D, Ma Y, Zhang C, Habets G, Burton EA, Wong B, Nguyen H, Kockx M, Andries L, Lestini B, Nolop KB, Lee RJ, Joe AK, Troy JL, Gonzalez R, Hutson TE, Puzanov I, Chmielowski B, Springer CJ, McArthur GA, Sosman JA, Lo RS, Ribas A, Marais R. RAS mutations in cutaneous squamous-cell carcinomas in patients treated with BRAF inhibitors. N Engl J Med. 2012 Jan 19;366(3):207-15. doi: 10.1056/NEJMoa1105358.
- Frederick DT, Salas Fragomeni RA, Schalck A, Ferreiro-Neira I, Hoff T, Cooper ZA, Haq R, Panka DJ, Kwong LN, Davies MA, Cusack JC, Flaherty KT, Fisher DE, Mier JW, Wargo JA, Sullivan RJ. Clinical profiling of BCL-2 family members in the setting of BRAF inhibition offers a rationale for targeting de novo resistance using BH3 mimetics. PLoS One. 2014 Jul 1;9(7):e101286. doi: 10.1371/journal.pone.0101286. eCollection 2014.
- Lacouture ME, Duvic M, Hauschild A, Prieto VG, Robert C, Schadendorf D, Kim CC, McCormack CJ, Myskowski PL, Spleiss O, Trunzer K, Su F, Nelson B, Nolop KB, Grippo JF, Lee RJ, Klimek MJ, Troy JL, Joe AK. Analysis of dermatologic events in vemurafenib-treated patients with melanoma. Oncologist. 2013;18(3):314-22. doi: 10.1634/theoncologist.2012-0333. Epub 2013 Mar 1.
- Ascierto PA, Ribas A, Larkin J, McArthur GA, Lewis KD, Hauschild A, Flaherty KT, McKenna E, Zhu Q, Mun Y, Dreno B. Impact of initial treatment and prognostic factors on postprogression survival in BRAF-mutated metastatic melanoma treated with dacarbazine or vemurafenib +/- cobimetinib: a pooled analysis of four clinical trials. J Transl Med. 2020 Aug 3;18(1):294. doi: 10.1186/s12967-020-02458-x.
- Sosman JA, Kim KB, Schuchter L, Gonzalez R, Pavlick AC, Weber JS, McArthur GA, Hutson TE, Moschos SJ, Flaherty KT, Hersey P, Kefford R, Lawrence D, Puzanov I, Lewis KD, Amaravadi RK, Chmielowski B, Lawrence HJ, Shyr Y, Ye F, Li J, Nolop KB, Lee RJ, Joe AK, Ribas A. Survival in BRAF V600-mutant advanced melanoma treated with vemurafenib. N Engl J Med. 2012 Feb 23;366(8):707-14. doi: 10.1056/NEJMoa1112302.
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 (실제)
2009년 9월 30일
기본 완료 (실제)
2010년 9월 27일
연구 완료 (실제)
2014년 6월 3일
연구 등록 날짜
최초 제출
2009년 7월 28일
QC 기준을 충족하는 최초 제출
2009년 7월 29일
처음 게시됨 (추정)
2009년 7월 30일
연구 기록 업데이트
마지막 업데이트 게시됨 (실제)
2017년 7월 25일
QC 기준을 충족하는 마지막 업데이트 제출
2017년 6월 26일
마지막으로 확인됨
2017년 6월 1일
추가 정보
이 연구와 관련된 용어
추가 관련 MeSH 약관
기타 연구 ID 번호
- NP22657
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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