Study of Selinexor and Doxorubicin in Advanced Soft Tissue Sarcomas
A Phase 1b Trial of Selinexor Plus Doxorubicin in Advanced Soft Tissue Sarcomas (STS)
This is a phase 1b study of investigational drug selinexor in combination with doxorubicin in patients with locally advanced or metastatic soft tissue sarcoma. The purpose of this study is to determine how safe and tolerable the combination is, as well as the best dose of the study drugs in this patient population.
Selinexor (also called KPT-330), works by trapping "tumor suppressor proteins" within the cell and thus causing the cancer cells to die or stop growing.
調査の概要
詳細な説明
This is a phase 1b study of investigational drug selinexor in combination with doxorubicin in patients with locally advanced or metastatic soft tissue sarcoma.
Patients will be screened for eligibility within 28 days of the start of the study drugs. In addition to standard tests and procedures, research tumor tissue (archival or fresh biopsy) will be collected for collection for pharmacodynamics. Participants will also be asked if they agree to optional biopsies at 6 cycles if their cancer is responding and at disease progression.
Eligible participants will then receive the study drugs in 21 day cycles. Selinexor will be given by mouth and doxorubicin will be given by vein, once a week, for 6 cycles.
Participants will be restaged every 2 cycles. If participants respond to treatment after 6 cycles, they may be able to continue the selinexor alone as a maintenance treatment until progression or unacceptable toxicity.
While receiving the study drug, many of the screening tests will be repeated. Additional tests and procedures include blood sample collection for pharmacokinetics and pharmacodynamics.
When participants stop the study drug permanently for any reason, an end of treatment visit, 28-day follow-up, and long term follow up every 90 days will occur.
研究の種類
入学 (実際)
段階
- フェーズ 1
連絡先と場所
研究場所
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-
Ontario
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Toronto、Ontario、カナダ、M5G 2M9
- Princess Margaret Cancer Centre
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参加基準
適格基準
就学可能な年齢
健康ボランティアの受け入れ
受講資格のある性別
説明
Inclusion Criteria:
- Written informed consent
- Patient must be willing and able to comply with scheduled visits, treatment plan, laboratory tests and other study procedures.
- Age ≥ 18 years.
- Patients must have histologically confirmed locally advanced/unresectable or metastatic soft tissue sarcoma.
- Patients must have not received prior doxorubicin.
- Patient must show evidence of progressive disease on study entry or newly diagnosed patients with de novo metastatic measurable disease
- Patient must have measureable disease as defined by RECIST 1.1.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
- Adequate hematopoietic function
- Adequate hepatic function:
- Adequate renal function
- Adequate cardiac function13
- Patients must agree to use methods of contraception as a agreed upon by the patient and study doctor
Exclusion Criteria:
- Patient is pregnant or lactating
- Radiation, chemotherapy, immunotherapy, any other systemic anticancer therapy, or participation in an investigational anti-cancer study ≤3 weeks prior to initiation of therapy.
- Major surgery within 4 weeks before initiation of therapy
- Unstable cardiovascular function
- Active, ongoing or uncontrolled active infection within one week prior to first dose.
- Malignancies other than disease under study within 2 years prior to Cycle 1, Day 1.
- Known to be HIV seropositive
- Known active hepatitis A, B, or C infection; or known to be positive for hepatitis C virus (HCV) RNA or hepatitis B virus (HBV) surface antigen (HBsAg)
- Patients with active CNS malignancy.
- Patients with any gastrointestinal dysfunctions that could interfere with the absorption of Selinexor or patients with significantly diseased or obstructed gastrointestinal tract or uncontrolled vomiting or diarrhea.
- Inability or unwillingness to take supportive medications such as anti-nausea and anti anorexia agents.
- In the opinion of the Investigator, patients who are significantly below their ideal body weight
- Serious psychiatric or medical conditions that could interfere with treatment
- Concurrent therapy with approved or investigational anticancer therapeutic agents
- Any condition that, in the opinion of the Investigator, would interfere with evaluation of the study regimen or interpretation of patient safety or study results
研究計画
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 |
|---|---|
|
実験的：Selinexor plus Doxorubicin
Selinexor will be given by mouth (orally) once a week: Dose Level -1 = 40 mg Dose Level 1 (Starting Dose) = 60 mg Dose Level 2 = 80 mg Doxorubicin will be given by vein (intravenously) at a dose of 75 mg/m2 once every 3 weeks. |
Selinexor is a Selective Inhibitor of Nuclear Export (SINE) compound that binds and inactivates Exportin 1 (XPO1), thereby forcing the nuclear retention of key tumor suppressor proteins (TSPs).
Doxorubicin is currently approved for various cancers.
Doxorubicin inhibits DNA synthesis and repair by inhibiting topoisomerase II and also by intercalation between base pairs on the DNA helix.
These actions result in the blockade of DNA and RNA synthesis and fragmentation of DNA.
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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 |
|---|---|---|
|
To evaluate the Incidence of Treatment-Emergent Adverse Events, graded and categorized according to the CTCAE v4.0.
時間枠：3 years
|
All adverse events will be tabulated and summarized by major organ category, grade, anticipation, and drug attribution.
SAE specific incidence and exact 95% confidence interval will be provided where appropriate.
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3 years
|
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To determine the recommended phase II dose (RP2D) of Selinexor in combination with doxorubicin
時間枠：3 years
|
The RP2D will be determined according to interim mTPI monitoring algorithm (Figure 5.1) using the dose determining set.
|
3 years
|
二次結果の測定
結果測定 |
時間枠 |
|---|---|
|
回答率
時間枠：3年
|
3年
|
|
Rate of Grade 3 Toxicities
時間枠：3 years
|
3 years
|
|
Progression-free Survival Rate
時間枠：3 years
|
3 years
|
協力者と研究者
捜査官
- 主任研究者：Albiruni Razak, M.D.、Princess Margaret Cancer Centre
研究記録日
主要日程の研究
研究開始 (実際)
一次修了 (実際)
研究の完了 (実際)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (見積もり)
学習記録の更新
投稿された最後の更新 (実際)
QC基準を満たした最後の更新が送信されました
最終確認日
詳しくは
本研究に関する用語
追加の関連 MeSH 用語
その他の研究ID番号
- SAR-002
個々の参加者データ (IPD) の計画
個々の参加者データ (IPD) を共有する予定はありますか?
医薬品およびデバイス情報、研究文書
米国FDA規制医薬品の研究
米国FDA規制機器製品の研究
米国で製造され、米国から輸出された製品。
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