Entolimod in Treating Patients With Locally Advanced or Metastatic Solid Tumors That Cannot Be Removed By Surgery
A Phase 1 Study to Evaluate the Safety and Pharmacokinetic Profile of CBLB502 in Patients With Advanced Cancers
調査の概要
詳細な説明
PRIMARY OBJECTIVES:
I. To determine the safety, tolerability, and maximum tolerated dose (MTD) of CBLB502 (entolimod) in patients with advanced cancers.
SECONDARY OBJECTIVES:
I. To assess any preliminary evidence of efficacy with the CBLB502 in patients with advanced cancers.
II. To evaluate pharmacokinetic (PK)/pharmacodynamic (PD) profiles of CBLB502 in patients with advanced cancers.
III. To characterize the effect, if any, of intramuscular or subcutaneous CBLB502 on QTcB.
TERTIARY OBJECTIVES:
I. To correlate pre-treatment tissue expression of toll-like receptor 5 (TLR5) with clinical activity (Response Evaluation Criteria In Solid Tumors [RECIST] tumor response) and PD response (as measured by cytokine levels) of CBLB502.
OUTLINE: This is a dose-escalation study.
Patients receive entolimod intramuscularly (IM) on day 1 and subcutaneously (SC) on days 4, 8, and 11. Treatment repeats every 6 weeks in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up for 30 days.
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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-
New York
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Buffalo、New York、アメリカ、14263
- Roswell Park Cancer Institute
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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 granted prior to initiation of any study-specific screening procedures, given with the understanding that the patient has the right to withdraw from the study at any time, without prejudice
- Histologically or cytologically confirmed locally advanced, inoperable or metastatic solid tumor for which no acceptable therapy exists
- Have an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
- Life expectancy greater than 3 months
- Platelet count >= 75 x 10^9/L
- Absolute neutrophil count (ANC) >= 1.5 x 10^9/L
- Hemoglobin (Hgb) >= 9 gm/dL
- Total bilirubin =< 1.5 x upper limit of normal (ULN)
- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 3 x ULN, regardless of the presence of liver metastases
- Creatinine =< 2 x ULN
- Left ventricular ejection fraction (LVEF) >=45% by echocardiogram (ECHO) or multi gated acquisition scan (MUGA)
- 12-Lead Electrocardiogram (ECG) with normal tracing or non-clinically significant changes that do not require medical intervention
- QTcB interval < 470 msec at any point prior to receiving the first dose of study drug (mean of replicate values, correction per institutional standard) and no history of Torsades des Pointes or other symptomatic QTcB abnormality
- Absence of orthostatic hypotension
Exclusion Criteria:
- Male and female subjects of child-bearing potential who do not agree to use double-barrier contraceptive measures, oral contraception, or avoidance of intercourse during the study and for 90 days after last investigational drug dose received
- Previous anti-cancer chemotherapy, immunotherapy or investigational agents =< 3 weeks prior to the first day of study defined treatment; palliative radiation < 2 weeks; patients who receive gamma knife radiosurgery for brain metastases are eligible if procedure was performed > 2 weeks before treated is started, is clinically stable and is not receiving corticosteroid therapy; ongoing hormonal therapies (such as, luteinizing hormone-releasing hormone [LHRH] antagonists, megestrol, anti-estrogens, or aromatase inhibitors) are allowed
- Previous treatment with a TLR5 agonist
- Patients with a known hypersensitivity to CBLB502 or to its excipients
- Presence of neutralizing antibodies to CBLB502
Patient has a history of cardiac dysfunction including any of the following:
- Myocardial infarction within the last 6 months, documented by persistent elevated cardiac enzymes; patients with persistent regional wall abnormalities on assessment of LVEF function are not eligible
- History of documents congestive heart failure (New York Heart Association [NYHA] functional classification III-IV) within 6 months
- Documented cardiomyopathy
- Diagnosed or suspected congenital QT syndrome
- Any history of second or third degree heart block (may be eligible if currently have a pacemaker)
- Heart rate < 50 beats/minute on pre-entry electrocardiogram
- Uncontrolled hypertension defined as systolic blood pressure > 160 mm Hg on 3 consecutive measurements prior to study enrollment
- Active clinically serious infections defined as >= Grade 2 according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0
- Substance abuse, medical, psychological, or social conditions that may, in the opinion of the Investigator, interfere with the patient's participation in the study or evaluation of the study results
- Any condition that is unstable or which could jeopardize the safety of the patient and his/her protocol compliance
- Known infection with human immunodeficiency virus (HIV) or hepatitis B or hepatitis C
- Patients who have been treated with any hematopoietic colony-stimulating growth factors (e.g., filgrastim [G-CSF], sargramostim [GM-CSF]) =< 2 weeks prior to starting study drug; erythropoietin or darbepoetin therapy, if initiated at least 2 weeks prior to enrollment, may be continued
- Women who are pregnant or breast feeding
- Patients receiving chronic treatment with steroids or another immunosuppressive agent; Note: topical applications (e.g., rash), inhaled sprays (e.g., obstructive airways diseases), eye drops or local injections (e.g., intra-articular) are allowed
- Uncontrolled diabetes mellitus defined as a HgbA1c > 7%
- Patients who have received chemotherapy or targeted anticancer therapy >= 3 weeks (6 weeks for nitrosourea, antibodies or mitomycin-C) prior to starting study drug must recover a Grade 1 toxicity before starting the trial
- Patient is unable or unwilling to abide by the study protocol or cooperate fully with the investigator
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:Treatment (entolimod)
Patients receive entolimod IM or SC on days 1, 4, 8, and 11.
Treatment repeats every 6 weeks in the absence of disease progression or unacceptable toxicity.
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相関研究
相関研究
Given IM or SC
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 |
---|---|---|
MTD of entolimod
時間枠:3 weeks
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Evaluated using National Cancer Institute (NCI)-Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0.
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3 weeks
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Safety of entolimod
時間枠:Up to 30 days post-treatment
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Evaluated using NCI-CTCAE Version 4.0.
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Up to 30 days post-treatment
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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 |
---|---|---|
Efficacy of entolimod in patients with advanced cancers in terms of objective response rate (ORR) and RECIST response
時間枠:Up to 3 months
|
ORR will be calculated as the number of patients with a confirmed complete or partial response divided by the total number of patients.
Tumor response will be summarized, and the 95% confidence interval for ORR (complete response [CR] + partial response [PR]) will be presented.
Evaluated using the RECIST criteria.
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Up to 3 months
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PK profiles of entolimod in patients with advanced cancers
時間枠:Pre-dose, 2, 4, 6, 8, 24 hours, post dose for, days 1, 4, 8 and 11
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Pre-dose, 2, 4, 6, 8, 24 hours, post dose for, days 1, 4, 8 and 11
|
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PD profiles of entolimod in patients with advanced cancers
時間枠:PD plasma: pre-dose, at 2, 4 and 6 hours post dose on day 1, 4, 8, 11, 15, 22, and 43
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PD plasma: pre-dose, at 2, 4 and 6 hours post dose on day 1, 4, 8, 11, 15, 22, and 43
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協力者と研究者
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 (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
その他の研究ID番号
- I 196111 (その他の識別子:Roswell Park Cancer Institute)
- NCI-2011-03565 (レジストリ識別子:CTRP (Clinical Trial Reporting Program))
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。
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