A Study of Vemurafenib in Previously Treated Patients With Metastatic Melanoma
2017年6月26日 更新者：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.
調査の概要
研究の種類
介入
入学 (実際)
132
段階
- フェーズ2
連絡先と場所
このセクションには、調査を実施する担当者の連絡先の詳細と、この調査が実施されている場所に関する情報が記載されています。
研究場所
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California
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Los Angeles、California、アメリカ、90095-6984
- UCLA - School of Medicine; Division of Hematology/Oncology
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Colorado
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Denver、Colorado、アメリカ、80262
- University of Colorado
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Florida
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Tampa、Florida、アメリカ、33612
- Moffitt Cancer Center
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Massachusetts
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Boston、Massachusetts、アメリカ、02215
- Beth Israel Deaconess Medical Center
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Boston、Massachusetts、アメリカ、02115
- Dana Farber Cancer Inst. ; Dept. of Medical Oncology
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Boston、Massachusetts、アメリカ、02114
- Massachusetts General Hospital;Hematology/ Oncology
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New York
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New York、New York、アメリカ、10036
- New York University Medical Center
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Pennsylvania
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Philadelphia、Pennsylvania、アメリカ、19104-4283
- Hospital of the Uni of Pennsylvania; Section of Hematology/Oncology
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Pittsburgh、Pennsylvania、アメリカ、15213
- University of Pittsburgh
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Tennessee
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Nashville、Tennessee、アメリカ、37232
- Vanderbilt-Ingram Cancer Ctr
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Texas
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Dallas、Texas、アメリカ、75246
- Texas Oncology-Baylor Sammons Cancer Center
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Houston、Texas、アメリカ、77030
- University of Texas M.D. Anderson Cancer Center
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New South Wales
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Newcastle、New South Wales、オーストラリア、2298
- Calvary Mater Newcastle; Melanoma Clinic
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Westmead、New South Wales、オーストラリア、2145
- Westmead Hospital; Medical Oncology and Pallative Care
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Victoria
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Melbourne、Victoria、オーストラリア、3000
- Peter Maccallum Cancer Institute; Medical Oncology
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参加基準
研究者は、適格基準と呼ばれる特定の説明に適合する人を探します。これらの基準のいくつかの例は、人の一般的な健康状態または以前の治療です。
適格基準
就学可能な年齢
18年歳以上 (大人、高齢者)
健康ボランティアの受け入れ
いいえ
受講資格のある性別
全て
説明
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
研究計画
このセクションでは、研究がどのように設計され、研究が何を測定しているかなど、研究計画の詳細を提供します。
研究はどのように設計されていますか？
デザインの詳細
- 主な目的：処理
- 割り当て：なし
- 介入モデル：単一グループの割り当て
- マスキング：なし（オープンラベル）
武器と介入
参加者グループ / アーム |
介入・治療 |
|---|---|
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実験的：シングルアーム
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960 mg b.i.d.
continuous oral dosing
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この研究は何を測定していますか？
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Best Overall Response (BOR) Assessed by an Independent Review Committee Using Response Evaluation Criteria In Solid Tumors (RECIST 1.1)
時間枠：From first treatment through September 27, 2010
|
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
|
二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Best Overall Response (BOR) Assessed by the Investigator Using Response Evaluation Criteria In Solid Tumors (RECIST 1.1)
時間枠：From first treatment through September 27, 2010
|
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)
時間枠：From first treatment through September 27, 2010
|
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)
時間枠：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)
時間枠：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
時間枠：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
時間枠：From first treatment through September 27, 2010
|
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
時間枠：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
時間枠：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
時間枠：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)
時間枠：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
時間枠：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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協力者と研究者
ここでは、この調査に関係する人々や組織を見つけることができます。
スポンサー
出版物と役立つリンク
研究に関する情報を入力する責任者は、自発的にこれらの出版物を提供します。これらは、研究に関連するあらゆるものに関するものである可能性があります。
一般刊行物
- 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.
研究記録日
これらの日付は、ClinicalTrials.gov への研究記録と要約結果の提出の進捗状況を追跡します。研究記録と報告された結果は、国立医学図書館 (NLM) によって審査され、公開 Web サイトに掲載される前に、特定の品質管理基準を満たしていることが確認されます。
主要日程の研究
研究開始 (実際)
2009年9月30日
一次修了 (実際)
2010年9月27日
研究の完了 (実際)
2014年6月3日
試験登録日
最初に提出
2009年7月28日
QC基準を満たした最初の提出物
2009年7月29日
最初の投稿 (見積もり)
2009年7月30日
学習記録の更新
投稿された最後の更新 (実際)
2017年7月25日
QC基準を満たした最後の更新が送信されました
2017年6月26日
最終確認日
2017年6月1日
詳しくは
この情報は、Web サイト clinicaltrials.gov から変更なしで直接取得したものです。研究の詳細を変更、削除、または更新するリクエストがある場合は、register@clinicaltrials.gov。 までご連絡ください。 clinicaltrials.gov に変更が加えられるとすぐに、ウェブサイトでも自動的に更新されます。
vemurafenibの臨床試験
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CytomX Therapeutics終了しましたリンパ腫 | 固形腫瘍アメリカ, オランダ, ポーランド, スペイン, ウクライナ, イギリス