A Phase 1, Open-Label, Dose Escalation Study of ANG1005 in Patients With Advanced Solid Tumors and Metastatic Brain Cancer
調査の概要
詳細な説明
This is a phase 1, multi-centre, sequential cohort, open-label, dose-escalation study of the safety, tolerability, and PK of ANG1005 in patients with solid tumors (with or without brain metastases). ANG1005 will be given by IV infusion once every 21 days (1 treatment cycle). Each patient will participate in only 1 dose group and will receive up to 6 cycles. Patients may receive additional cycles of ANG1005 if there is no evidence of tumor progression, there is recovery to ≤Grade 1 or baseline nonhematologic, ANG1005-related toxicity (except alopecia), the absolute neutrophil count is ≥1.5 x 109/L, and the platelet count is ≥100 x 109/L.
Initially, cohorts of 1 - 3 patients will be enrolled into each dose group. Dose escalation by dose doubling will be done for the first 3 dose groups followed by a modified Fibonacci dose escalation scheme with increases of 67%, 50%, 40% and 33% thereafter. If 1 or more patients in a cohort experience an emergent ≥ Grade 2 drug-related toxicity during the first treatment cycle, then a minimum of 3 patients will be enrolled into that, and all subsequent cohort(s) and dose doubling will be stopped if applicable.
If > 1 patient in a cohort experience a dose limiting toxicity (DLT) during the first treatment cycle, defined as any of the following that are both treatment-emergent and at least possibly related to ANG1005: i) Any Grade 3 or 4 nonhematologic toxicity, ii) Febrile neutropenia, iii) Grade 4 neutropenia of ≥7 days duration, and/or iv) Any Grade 4 thrombocytopenia, then dose escalation will stop and prior doses will be explored as the maximum tolerated dose (MTD), that dose-level at which ≤1 of 6 patients in a cohort develop an emergent DLT).
Once the MTD is established, approximately 14 patients will be enrolled at that dose-level in order to further assess the safety and tolerability of ANG1005, the PK profile of ANG1005 at the MTD, and the preliminary anti-tumor activity of ANG1005 in patients with solid tumors (with or without brain metastases).
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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Ohio
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Canton、Ohio、アメリカ、44718
- Gabrail Cancer Center
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Texas
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Houston、Texas、アメリカ、77030
- University of Texas, MD Anderson Cancer Center
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San Antonio、Texas、アメリカ、78229
- UT Health Science Center, Cancer Therapy and Research Center
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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
- Histologically or cytologically confirmed metastatic or advance-stage solid tumor that has progressed following standard therapy or for which, in the opinion of the Investigator, no standard effective therapy is available; patients without brain metastases may be enrolled into the dose-escalation part of the study
- Patients enrolled into the expanded MTD cohort must have shown unequivocal evidence of brain metastases
- Male and female patients.
- Age ≥18 years
- Eastern Cooperative Oncology Group (ECOG) performance status 0-2
- An expected survival of at least 3 months
- Measurable disease according to RECIST criteria; patients with brain metastases must have at least one measurable lesion in the brain, according to RECIST criteria
- Male and female subjects who are not surgically sterile or post-menopausal must agree to use reliable methods of birth control for the duration of the study and for 90 days after the last dose of study drug administration; male partners of female subjects should use condoms for the duration of the study, and for 90 days after the last dose of study drug administration
Exclusion Criteria:
- Chemotherapy, radiotherapy (except palliative radiation delivered to <20% of bone marrow), or investigational agents within 4 weeks before the first dose of study drug. Biologic therapy (such as 13-cis-retinoic acid, thalidomide, tamoxifen, celebrex, erlotinib, imatinib, vorinostat, and lapatinib) and immunotherapy (such as interferon a or b, cdx-110 (EGFR vIII vaccine), interleukin 2, thalidomide) within 1 week before the first dose of study drug. Bevacizumab within 6 weeks before the first dose of study drug
- Pregnant or lactating females
- Any acute viral, bacterial, or fungal infection that requires parenteral therapy within 14 days prior to study treatment
- Known severe hypersensitivity to paclitaxel
- Severe toxicity with previous taxane treatment
- Treatment with P450 CYP 3A4 or CYP 2C8 enzyme-inducing anti-convulsant drugs within 14 days prior to treatment with study drug
- Patients with inadequate hematological, liver, and renal function
- Known or suspected acute or chronic active Hepatitis B, Hepatitis C, or HIV/AIDS
- Patients with unstable or uncompensated respiratory, cardiac, hepatic or renal disease or any other organ system dysfunction, medical condition, or laboratory abnormality which, in the opinion of the Investigator, would either comprise the patient's safety or interfere with the evaluation of the test material
- Evidence of persistent Grade 2 or greater neurotoxicity
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
- 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：1
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21日に1回の点滴
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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 |
時間枠 |
|---|---|
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To characterize the safety and tolerability of intravenously administered ANG1005 in patients with advanced solid tumors and metastatic brain cancer.
時間枠：On-going
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On-going
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To identify the maximum tolerated dose (MTD) of ANG1005 in patients with advanced solid tumors and metastatic brain cancer.
時間枠：End of dose escalation
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End of dose escalation
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二次結果の測定
結果測定 |
時間枠 |
|---|---|
|
ANG1005 の薬物動態 (PK) を調べるため。
時間枠：学習の終了
|
学習の終了
|
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MTD で ANG1005 の安全性と忍容性を確認するため。
時間枠：用量漸増の終了
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用量漸増の終了
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ANG1005 の免疫原性を評価するため。
時間枠：学習の終了
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学習の終了
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To obtain preliminary information on the antitumor activity of ANG1005 in patients with advanced solid tumors with brain metastases.
時間枠：On-going
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On-going
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協力者と研究者
スポンサー
出版物と役立つリンク
便利なリンク
研究記録日
主要日程の研究
研究開始
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 (見積もり)
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
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