Safety and Efficacy Study of Vemurafenib and High-dose Interferon Alfa-2b in Melanoma (12-107)
2018年4月1日 更新者：John Kirkwood
Dose-seeking and Efficacy Study of the Combination of the BRAF Inhibitor Vemurafenib and High-dose Interferon Alfa-2b for Therapy of Advanced Melanoma
This is a dose-seeking and efficacy study of combined BRAF Inhibitor Vemurafenib and High-dose Interferon alfa-2b for therapy of advanced melanoma.
調査の概要
詳細な説明
- Dose-selection and dose-expansion study of combination therapy with high-dose interferon alfa-2b and vemurafenib.
- Vemurafenib at standard dosing with a 2 week lead-in period to exploit potential immunomodulatory effects. Concurrent HDI following this (week 2 onwards) at standard induction (4 weeks) and maintenance (48 weeks) doses.
- Modified Storer's "up and down" dose escalation schema using 3 fixed dose levels for HDI and a fixed sample size that allows efficient identification of recommended phase II dose.
- 36-63 patients will be enrolled depending on toxicity parameters. oIn the dose-selection portion, 3 patients will be enrolled per dose level, starting from the lowest dose level. Enrollment will occur serially allowing for the observation of toxicity during the observation period.
oIterative enrollment of up to 3 subjects per cohort will be continued until a total of 30 evaluable subjects have been enrolled.
oThe dose level at which the RLT rate is the closest to 1/3 will be considered as RP2D.
oDuring the dose-expansion portion of the trial, depending on the number of patients treated at RP2D during the dose-selection portion, additional patients may be enrolled - the accrual target is 36 patients treated at RP2D.
研究の種類
介入
入学 (実際)
7
段階
- フェーズ 1
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
-
-
Pennsylvania
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Pittsburgh、Pennsylvania、アメリカ、15232
- Hillman Cancer Center
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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:
- Patients must have a written informed consent.
- 18 years of age.
- Patients must have histologically confirmed recurrent stage III or stage IV melanoma (AJCC 7th edition classification).
- BRAF V600E and V600K mutated
- Cutaneous squamous cell carcinomas (SCC) lesions identified at baseline must be excised. Adequate wound healing is required prior to study entry.
- Patients must have measurable disease as defined by the Response Evaluation Criteria in Solid Tumors v1.1.
Patients must have adequate hematologic, renal, and liver function:
- WBC ≥ 3,000/mm3
- ANC ≥ 1500
- Hb ≥ 9g/dL (women) or ≥ 11g/dL (men) (supportive transfusions will be allowed during induction and maintenance phases to maintain these levels)
- Platelets ≥ 100,000/mm3 (supportive transfusions will be allowed during induction and maintenance phases to maintain these levels)
- Serum Creatinine ≤ 1.5 x upper limit of normal (ULN)
- Serum Bilirubin ≤ 1.5 x ULN
- Serum AST/ALT ≤ 2.5 x ULN
- EKG documenting normal intervals.
- Fully recovered from any effects of major surgery, and be free of significant detectable infection.
- ECOG performance status of 0 or 1.
- Free of active brain metastases by contrast-enhanced CT/MRI scans within 4 weeks prior to starting the study drugs.
- Female patients of child bearing potential must have a negative pregnancy test (within 7 days from the time of randomization).
Exclusion Criteria:
- Serious illnesses, such as: cardiovascular disease (uncontrolled congestive heart failure, uncontrolled hypertension, cardiac ischemia, myocardial infarction, and severe cardiac arrhythmia), bleeding disorders, symptomatic autoimmune diseases, severe obstructive or restrictive pulmonary diseases, uncontrolled endocrine disorders (hypothyroidism, hyperthyroidism and diabetes mellitus), retinopathy, active systemic infections, and inflammatory bowel disorders. This includes known HIV or AIDS-related illness, or active HBV and HCV.
- Prior therapy (except for adjuvant immunotherapy) with a BRAF and/or MEK and/or ERK inhibitors.
- Refractory nausea, vomiting, small bowel resection or any other gastrointestinal ailment that would preclude study drug absorption.
Cardiac abnormalities
- Mean QTc interval ≥ 480 msec at screening.
- Recent ACS/AMI - defined as within 24 weeks prior to screening.
- Recent PCI/PTCA - defined as within 24 weeks prior to screening.
- Recent malignant cardiac arrhythmias - all except sinus arrhythmia within 24 weeks prior to screening.
- Symptomatic heart failure - NYHA Class ≥ II symptoms.
- Active infection or antibiotics within one-week prior to study, including unexplained fever Any significant psychiatric disease, medical intervention, or other condition, which in the opinion of the principal investigator, could prevent adequate informed consent or compromise participation in the clinical trial.
- Systemic steroid or other immunosuppressive therapy within 4 weeks of starting the study.
- Lactating females or pregnant females.
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：非ランダム化
- 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 |
|---|---|
|
実験的：Vemurafenib + IFNα-2b (10 MU/m2/d)
Vemurafenib + High-dose Interferon alfa-2b (10 MU/m2/d)
|
•Vemurafenib at standard dosing with a 2 week lead-in period to identify potential effects.
IFNα-2b following this (week 2 onwards) at standard induction (4 weeks) and maintenance (48 weeks) doses.
他の名前：
Vemurafenib is a prescription medicine used to treat melanoma, that has spread to other parts of the body or cannot be removed by surgery, and that has a certain type of abnormal "BRAF" gene.
他の名前：
|
|
実験的：Vemurafenib + IFNα-2b(15 MU/m2/d)
Vemurafenib + High-dose Interferon alfa-2b (15 MU/m2/d)
|
•Vemurafenib at standard dosing with a 2 week lead-in period to identify potential effects.
IFNα-2b following this (week 2 onwards) at standard induction (4 weeks) and maintenance (48 weeks) doses.
他の名前：
Vemurafenib is a prescription medicine used to treat melanoma, that has spread to other parts of the body or cannot be removed by surgery, and that has a certain type of abnormal "BRAF" gene.
他の名前：
|
|
実験的：Vemurafenib + IFNα-2b (20 MU/m2/d)
Vemurafenib + High-dose Interferon alfa-2b (20 MU/m2/d)
|
•Vemurafenib at standard dosing with a 2 week lead-in period to identify potential effects.
IFNα-2b following this (week 2 onwards) at standard induction (4 weeks) and maintenance (48 weeks) doses.
他の名前：
Vemurafenib is a prescription medicine used to treat melanoma, that has spread to other parts of the body or cannot be removed by surgery, and that has a certain type of abnormal "BRAF" gene.
他の名前：
|
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 |
|---|---|---|
|
Number of Participants with Adverse Events to determine Ph II dose
時間枠：12-24 months from study start
|
At each dose level, the number of patients experiencing Adverse Events over their course of treatment will be characterized by type of Adverse Event and grade using NCI CTCAE (v4.0), and by time of onset in relation to the first day of therapy.
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12-24 months from study start
|
二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Progression Free and overall survival (Efficacy)
時間枠：48 months
|
•Progression Free Survival will be evaluated at 6 months using the Kaplan-Meier method.
Overall Survival will be measured from the initial date of treatment to the recorded date of death, and analyzed similarly to Progression Free Survival.
Overall Survival will also be analyzed with the Kaplan-Meier method.
The complete response rate and partial response rate will be estimated by the proportion of patients with a best response respectively by RECIST criteria.
|
48 months
|
その他の成果指標
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Improve tumor STAT signaling
時間枠：48 months
|
Melanoma metastases removed from patients pretreatment, post-BRAFI alone and Post B-RAF+ will be analyzed for expression of IFNAR1 and immunologically relevant molecules such as HLA antigens, APM components and MA; these results will be correlated with T cell infiltration.
In addition the metastases will be tested for extent of melanoma cell proliferation and apoptosis.
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48 months
|
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
捜査官
- 主任研究者：John Kirkwood, MD、University of Pittsburgh Medical Center
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)
2013年10月1日
一次修了 (実際)
2016年11月1日
研究の完了 (実際)
2016年12月1日
試験登録日
最初に提出
2013年8月27日
QC基準を満たした最初の提出物
2013年9月11日
最初の投稿 (見積もり)
2013年9月17日
学習記録の更新
投稿された最後の更新 (実際)
2018年4月3日
QC基準を満たした最後の更新が送信されました
2018年4月1日
最終確認日
2018年4月1日
詳しくは
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