悪液質を伴う転移性がん患者における AV-380 の用量漸増研究
悪液質およびGDF-15レベルの上昇を伴う転移性がん患者を対象とした、標準治療化学療法と併用したAV-380の第1相用量漸増研究
This open label ascending dose study is designed to evaluate the safety, pharmacokinetics (PK), pharmacodynamics (PD), and immunogenicity of AV-380 in cancer patients with Cachexia. AV-380 is an immunoglobulin (Ig) G1 monoclonal antibody (mAb) intended to bind circulating human growth differentiation factor 15 (GDF-15), a cytokine involved in cancer-induced cachexia.
調査の概要
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
-
-
California
-
Beverly Hills、California、アメリカ、90211
- Beverly Hills Cancer Center
-
Lakewood、California、アメリカ、90712
- Cancer and Blood Specialty Clinic
-
Newport Beach、California、アメリカ、92663
- Hoag Memorial Hospital
-
-
Connecticut
-
Hartford、Connecticut、アメリカ、06102
- Hartford Hospital
-
-
Florida
-
Orlando、Florida、アメリカ、32804
- Advent Health Orlando Hospital
-
-
Nebraska
-
Omaha、Nebraska、アメリカ、68130
- Nebraska Cancer Specialists
-
-
New Jersey
-
East Brunswick、New Jersey、アメリカ、08816
- Astera Cancer Care
-
-
New York
-
Shirley、New York、アメリカ、11967
- New York Cancer And Blood Specialists
-
-
Oregon
-
Portland、Oregon、アメリカ、97239
- Oregon Health and Science University
-
-
South Carolina
-
Charleston、South Carolina、アメリカ、29425
- MUSC Hollings Cancer Center
-
-
Tennessee
-
Nashville、Tennessee、アメリカ、37232
- Vanderbilt University Henry-Joyce Cancer Clinic
-
-
Texas
-
Kingwood、Texas、アメリカ、77339
- Community Clinical Trials
-
-
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:
-
Patient must be ≥ 18 years of age at the time of signing the informed consent.
-
Patients with histologically confirmed solid tumor cancer who are actively receiving SoC therapy for this cancer.
-
Patients with cachexia as defined by Fearon criteria:
- Weight loss > 5% over past 6 months (in absence of simple starvation), or
- BMI < 20 kg/m2 and any degree of weight loss > 2%, or
- Sarcopenia and any degree of weight loss > 2%
-
Patients with life expectancy ≥ 3 months
Exclusion Criteria:
- History of allergic or anaphylactic reaction to any monoclonal antibody (IgG protein) or molecules made of components of monoclonal antibody
- Known brain metastases or cranial epidural disease unless adequately treated with radiotherapy and/or surgery (including radiosurgery) and stable for at least 2 weeks before first dose of study treatment.
- Myocardial infarction or heart failure of New York Heart Association Grade 3-4 within 3 months prior to start of protocol therapy
- Uncontrolled pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently)
- Cachexia is caused by other reasons (e.g., severe chronic obstructive pulmonary disease, heart failure, or HIV/AIDS), or the patient has uncontrolled reversible causes of reduced oral food intake, including, but not limited to, oral mucositis, nausea/vomiting, diarrhea, and/or obstruction, impairing the patient's ability to eat as determined by the Investigator.
- Patients receiving tube feedings or parenteral nutrition at the time of Screening.
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：順次割り当て
- 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：Dose Escalation Cohorts
Experimental: Dose escalation cohorts of AV-380 administered by IV infusion |
AV-380 is an immunoglobulin (Ig) G1 monoclonal antibody (mAb) intended to bind circulating human growth differentiation factor 15 (GDF-15), a cytokine involved in cancer-induced cachexia. |
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 |
|---|---|---|
|
Assessment of adverse events (AEs)
時間枠：From enrollment to the last follow-up visit approximately 60-days post dose
|
AEs as characterized by incidence, type, frequency, and severity (graded according to National Cancer Institute Common Terminology Criteria for Adverse Events [NCI CTCAE]) |
From enrollment to the last follow-up visit approximately 60-days post dose
|
|
Toxicity
時間枠：While receiving study drug (up to 4 months)
|
Dose-limiting Toxicity (DLT) events observed at increasing doses of AV-380 |
While receiving study drug (up to 4 months)
|
|
Laboratory Abnormalities
時間枠：From enrollment to the last follow-up visit approximately 60-days post dose.
|
Laboratory abnormalities as characterized by type, frequency, severity (graded according to NCI-CTCAE v5.0) and timing. |
From enrollment to the last follow-up visit approximately 60-days post dose.
|
二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Cmax
時間枠：From first dose to the last follow-up visit approximately 60-days post dose.
|
Maximum observed plasma concentration for AV-380 |
From first dose to the last follow-up visit approximately 60-days post dose.
|
|
Tmax
時間枠：From first dose to the last follow-up visit approximately 60-days post dose
|
Time to reach the Cmax for AV-380 |
From first dose to the last follow-up visit approximately 60-days post dose
|
|
AUC(0-t)
時間枠：From first dose to the last follow-up visit approximately 60-days post dose.
|
Area under the plasma concentration-time curve from zero time to the last measurable point for AV-380 |
From first dose to the last follow-up visit approximately 60-days post dose.
|
その他の成果指標
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
GDF-15の血清レベル
時間枠：登録から最後のフォローアップまで、約60日後の投与後に訪問します。
|
登録から最後のフォローアップまで、約60日後の投与後に訪問します。
|
|
|
Immunogenicity
時間枠：From first dose to the last follow-up visit approximately 60-days post dose.
|
Serum levels of Anti-Drug Antibody (ADA) against AV-380 and their potential relationship with AEs and serum levels of GDF-15 |
From first dose to the last follow-up visit approximately 60-days post dose.
|
|
Weight
時間枠：From enrollment to the last follow-up visit approximately 60-days post dose.
|
Change from baseline body weight during the study |
From enrollment to the last follow-up visit approximately 60-days post dose.
|
|
Patient-Reported Outcomes
時間枠：From enrollment to the end of treatment, approximately 4 months
|
Change from baseline in the following questionnaires: Functional Assessment of Anorexia Cachexia Therapy (FAACT); Patient global impression of severity (PGI-S) and patient global impression of change (PGI-C) for appetite, fatigue, and physical activity. |
From enrollment to the end of treatment, approximately 4 months
|
|
Lumbar (L3) Skeletal Muscle Index (L3SMI)
時間枠：From enrollment to the end of treatment, approximately 4 months
|
Measurement of a cross-sectional area of muscle at the level of the third lumbar vertebra (L3) using computed tomography (CT) scan |
From enrollment to the end of treatment, approximately 4 months
|
|
Physical Function
時間枠：From enrollment to the end of treatment, approximately 4 months
|
Change from baseline in physical function endpoints, including Short Physical Performance Battery test and digital measures of non-sedentary time |
From enrollment to the end of treatment, approximately 4 months
|
|
Albumin and CRP
時間枠：From enrollment to the last follow-up visit approximately 60-days post dose.
|
Change from baseline in albumin and CRP levels |
From enrollment to the last follow-up visit approximately 60-days post dose.
|
|
Tumor status
時間枠：From enrollment to the last follow-up visit approximately 60-days post dose.
|
Evaluate the effect of AV-380 on tumor burden and tumor status, per Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST 1.1) |
From enrollment to the last follow-up visit approximately 60-days post dose.
|
|
Biomarkers
時間枠：From first dose to the last follow-up visit approximately 60-days post dose.
|
including activin A and cytokine levels (e.g., monocyte chemoattractant protein-1 [MCP-1] and proinflammatory) |
From first dose to the last follow-up visit approximately 60-days post dose.
|
協力者と研究者
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 (実際)
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
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。