Ruxolitinib in Patients With Breast Cancer
2017年1月3日 更新者：Nancy Lin, MD、Dana-Farber Cancer Institute
Phase II Study of Ruxolitinib (INCB018424) in Patients With PSTAT3+ Breast Cancer
Ruxolitinib is a drug which blocks the Janus tyrosine Kinase (JAK) signaling pathway.
It is thought that this pathway might be important in certain types of breast cancer, and that blocking this pathway might lead to anti-cancer effects.
This study is testing the effects of ruxolitinib in patients with breast cancer.
調査の概要
詳細な説明
Objectives:
Primary
- The primary objective of this two-stage, phase II study is to estimate the objective response rate to ruxolitinib in patients with metastatic or unresectable locally advanced breast cancer which is pStat3+ and which has progressed on at least one line of chemotherapy for advanced disease, and/or has recurred within 12 months of completion of neoadjuvant/adjuvant chemotherapy.
Secondary
- To describe the toxicity profile
- To evaluate clinical benefit rate (CR + PR + SD >/= 24 weeks)
- To estimate progression-free and overall survival
Exploratory
- To explore whether baseline hs-CRP level higher than the group median is associated with objective response
- To explore whether baseline IL-6 level higher than the group median is associated with objective response
- To describe hs-CRP level over time, and to describe the proportion of patients with a) hs-CRP > 3mg/L at baseline, on treatment, and at time of progression, and b) hs-CRP > 1mg/L at baseline, on treatment, and at time of progression
- To describe IL-6 level over time, and to describe the proportion of patients with IL-6 level above the upper limit of normal at baseline, on treatment, and at time of progression
- To describe pStat3 status by IHC in baseline metastatic biopsies
- To describe pStat3 status by IHC in on-study biopsies
- To describe pStat3 status by IHC in the time of progression biopsy samples
- To characterize archival and metastatic biopsy samples using triple immunofluorescence for CD44, CD24, and pStat3
- To characterize archival and metastatic biopsy samples using a previously characterized pStat3 gene signature
- To characterize circulating tumor cells (CTCs) for CD44, CD24, and pStat3 at baseline and time of progression
研究の種類
介入
入学 (実際)
21
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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Massachusetts
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Boston、Massachusetts、アメリカ、02215
- Dana-Farber Cancer Institute
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Boston、Massachusetts、アメリカ、02114
- Massachusetts General Hospital
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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:
- Histologically or cytologically confirmed invasive breast cancer
- Must have known ER, PR and HER2 status
- Either, Triple Negative Metastatic Breast Cancer or
- Inflammatory Breast Cancer with any ER, PR HER2 status
- Availability of archival tissue specimen suitable for pStat3 testing
- Life expectancy of greater than 3 months
- Measurable disease by RECIST
- At least one prior chemotherapy regimen for treatment of metastatic breast cancer and/or recurrence within 12 months of completion of neoadjuvant/adjuvant chemotherapy or
- For patients with inflammatory breast cancer but no distant metastases, progression through standard neoadjuvant chemotherapy is required
Exclusion Criteria:
- Pregnant or breastfeeding
- Active brain metastases
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to ruxolitinib
- Clinically significant malabsorption syndrome
- Concurrent use of medications/substances that are strong inhibitors of CY3A4
- No uncontrolled intercurrent illness
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 |
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実験的：Ruxolitinib-Cohort A
Patients received Ruxolitinib 25 mg twice daily for up to 12 cycles (cycle duration=28 days) until evidence of disease progression or unacceptable toxicity.
Patients enrolled sequentially into two possible cohorts based on pStat3+ expression score by central testing: Cohort A - moderate to high positive status defined as a score of >/=5 by central testing or Cohort B - low positive status defined as a score of 3-4.
Each cohort was evaluated with a 2 stage design.
Cohort B only opened if 2 objective responses were observed in 1st stage Cohort A patients (n=21).
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他の名前：
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実験的：Ruxolitinib-Cohort B
Patients received Ruxolitinib 25 mg twice daily for up to 12 cycles (cycle duration=28 days) until evidence of disease progression or unacceptable toxicity.
Patients enrolled sequentially into two possible cohorts based on pStat3+ expression score by central testing: Cohort A - moderate to high positive status defined as a score of >/=5 by central testing or Cohort B - low positive status defined as a score of 3-4.
Each cohort was evaluated with a 2 stage design.
Cohort B only opened if 2 objective responses were observed in 1st stage Cohort A patients (n=21).
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他の名前：
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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 |
|---|---|---|
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Objective Response Rate
時間枠：Disease was evaluated radiologically at baseline and every 8 weeks on treatment; Treatment continued until disease progression or unacceptable toxicity up to 12 cycles. Treatment duration was a median of 2 cycles range (1-5).
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The objective response rate (ORR) was defined as achieving complete response (CR) or partial response (PR) based on RECIST 1.1 criteria on treatment.
Per RECIST 1.1 for target lesions: CR is complete disappearance of all target lesions and PR is at least a 30% decrease in the sum of longest diameter (LD) of target lesions, taking as reference baseline sum LD.
PR or better overall response assumes at a minimum incomplete response/stable disease (SD) for the evaluation of non-target lesions and absence of new lesions.
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Disease was evaluated radiologically at baseline and every 8 weeks on treatment; Treatment continued until disease progression or unacceptable toxicity up to 12 cycles. Treatment duration was a median of 2 cycles range (1-5).
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二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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Clinical Benefit Rate
時間枠：Disease was evaluated radiologically at baseline and every 8 weeks on treatment; Treatment continued until disease progression or unacceptable toxicity up to 12 cycles. Treatment duration was a median of 2 cycles range (1-5).
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Clinical benefit rate (CBR) was defined as achieving complete response (CR), partial response (PR), or stable disease (SD) for 24 weeks or longer based on RECIST 1.1 criteria on treatment.
Per RECIST 1.1 for target lesions: CR is complete disappearance of all target lesions and PR is at least a 30% decrease in the sum of longest diameter (LD) of target lesions, taking as reference baseline sum LD.
PD is at least a 20% increase in sum LD of target lesions (smallest sum LD reference), new lesions, and/or unequivocal progression of existing non-target lesions.
Stable disease (SD) is defined as any condition not meeting the above criteria.
SD needed to be a minimum 24 weeks in duration.
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Disease was evaluated radiologically at baseline and every 8 weeks on treatment; Treatment continued until disease progression or unacceptable toxicity up to 12 cycles. Treatment duration was a median of 2 cycles range (1-5).
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Overall Survival
時間枠：In long-term follow-up, patients were followed for survival every 4 months for up to 2 years. Median follow-up in this study cohort was 4.5 months (range 0.6-21.9).
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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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In long-term follow-up, patients were followed for survival every 4 months for up to 2 years. Median follow-up in this study cohort was 4.5 months (range 0.6-21.9).
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Progression-Free Survival
時間枠：Disease was evaluated radiologically every 8 weeks on treatment through 12 cycles and in long-term follow-up every 4 months for up to 2 years. Median follow-up in this study cohort was 4.5 months (range 0.6-21.9).
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Progression-free survival based on the Kaplan-Meier method is defined as the duration of time from study entry to documented disease progression (PD) or death.
Per RECIST 1.1 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 equivocal progression of non-target lesions.
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Disease was evaluated radiologically every 8 weeks on treatment through 12 cycles and in long-term follow-up every 4 months for up to 2 years. Median follow-up in this study cohort was 4.5 months (range 0.6-21.9).
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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。
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
2012年6月1日
一次修了 (実際)
2015年6月1日
研究の完了 (実際)
2016年6月1日
試験登録日
最初に提出
2012年3月20日
QC基準を満たした最初の提出物
2012年3月22日
最初の投稿 (見積もり)
2012年3月26日
学習記録の更新
投稿された最後の更新 (実際)
2017年2月23日
QC基準を満たした最後の更新が送信されました
2017年1月3日
最終確認日
2017年1月1日
詳しくは
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