Study of Pembrolizumab Combined With Anlotinib in the First Line Therapy for R/M HNSCC With CPS≥1
A Prospective Clinical Study to Evaluate the Efficacy and Safety of Pembrolizumab Combined With Anlotinib in First-line Treatment for Patients With of R/M HNSCC PD-L1 CPS≥1
調査の概要
詳細な説明
研究の種類
入学 (予想される)
段階
- フェーズ2
連絡先と場所
研究連絡先
- 名前:Yuankai Shi, MD
- 電話番号:+86-10-87788293
- メール:syuankaipumc@126.com
研究場所
-
-
Beijing
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Beijing、Beijing、中国、100021
- 募集
- National Cancer Center/Cancer Hospitial,Chinese Academy of Medical Sciences and Peking Union Medical College
-
コンタクト:
- Yuankai Shi, MD
- 電話番号:+86-10-87788293
- メール:syuankaipumc@126.com
-
-
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:
- 1) Voluntarily sign written informed consent before screening; 2) Age ≥18 years old; 3) ECOG physical status score 0-1; 4) Histologically or cytologically confirmed squamous cell carcinoma of the head and neck (HNSCC) with primary site of oral cavity, oropharynx, hypopharynx or larynx; 5) Recurrent and/or metastatic HNSCC without indications of local radical treatment; 6) According to the efficacy evaluation criteria for solid tumors (RECIST version 1.1), at least one measurable lesion can be selected as the target lesion after receiving previous radiotherapy only if there has been definite disease progression 3 months after the end of radiotherapy; 7) Sufficient tumor tissue samples for PD-L1 immunohistochemical detection; 8) Expected survival of more than 3 months; 9) The main organs function normally, that is, they meet the following criteria: I. Blood routine (no blood transfusion, erythropoietin (EPO), granulocyte colony-stimulating factor (G-CSF) or granulocyte-macrophage colony-stimulating factor (GM-CSF) treatment within 14 days before screening examination) : neutrophils ≥1.5× L09 /L, platelets ≥100×109/L, hemoglobin ≥90g/L; II. Liver function: ALT and AST, ALT and AST≤3×ULN in patients without liver metastasis, ALT and AST≤5×ULN in patients with liver metastasis;Total bilirubin (TBil) ≤1.5×ULN (Gilbert syndrome patients, ≤3 ×ULN); Iii. Renal function: Serum creatinine (CR) ≤1.5×ULN or creatinine clearance (CCR) ≥50ml/ min (subjects receiving carboplatin) or ≥60ml/ min (subjects receiving cisplatin); IV. Coagulation function: APTT, INR, PT ≤1.5×ULN; V. Echocardiography: left ventricular ejection fraction (LVEF) ≥50%; 10) Women should agree to use contraceptives (such as intrauterine devices [IUDs], contraceptives or condoms) during the study period and for 6 months after the end of the study;Negative blood pregnancy test within 7 days prior to study enrolment and must be non-lactating;Men should agree to use contraception during the study period and within 6 months after the end of the study period.
Exclusion Criteria:
1) The patient had necrotic lesions and was judged by the investigator to be at risk of massive bleeding; 2) A history of hypersensitivity to amlotinib or pabrizumab or any excipients; 3) Previous use of antiangiogenic drugs (such as amlotinib, apatinib, bevacizumab, Endox, etc.); 4) The patient is using (or cannot be discontinued within 1 week prior to the first dosing of the study treatment) a Chinese herbal medicine indicated for antitumor use; 5) poorly controlled pleural effusion, pericardial effusion or ascites requiring frequent drainage;Patients with indwelling catheters (such as the Pleurx ® catheter) are allowed to participate; 6) At the beginning of study treatment, there was still an uncured toxic reaction from previous treatment and CTCAE 5.0 was higher than level 1 (except for alopecia); 7) Spinal cord compression or symptomatic untreated brain or spinal cord metastases (except asymptomatic, stable condition, and no need for steroid therapy for 4 weeks prior to study treatment); 8) poorly controlled tumor-related pain.Patients who require analgesics must receive a steady dose before entering the study.Symptomatic lesions suitable for palliative radiotherapy (e.g., bone metastases or metastases leading to nerve damage) should be treated before enrolment.Prior to enrolment, local-regional treatment of asymptomatic metastatic lesions with further growth that may result in functional deficits or intractable pain (e.g., epidural metastases currently not associated with spinal cord compression) should be considered, if appropriate.
9) Hepatitis B, hepatitis C or human immunodeficiency virus (HIV antibody positive).Patients with positive hepatitis B antibodies were only eligible to participate in the study if they had HBV DNA ˂2000cps/ml.Patients with hepatitis C antibody positive were eligible to participate in the study only if polymerase chain reaction showed HCV RNA negative; 10) Randomization of malignancies other than advanced head and neck squamous cell carcinoma with negligible risk of metastasis or death and expected radical outcome after treatment within the first 5 years (e.g.,Adequately treated carcinoma in situ of the cervix, basal or squamous cell skin cancer, localized prostate cancer for radical treatment, and ductal carcinoma in situ for radical surgery); 11) Had major surgery other than a diagnosis of advanced head and neck squamous cell carcinoma within 28 days prior to randomization or was expected to require major surgery during the study period; 12) patients who have had previous bone marrow transplantation or previous solid organ transplantation; 13) Any live vaccine (for example, vaccines against infectious diseases, such as influenza, varicella, etc.) was given within the first 4 weeks (28 days) of randomization; 14) any factors that may affect the patient's oral administration, such as inability to swallow, post-gastrointestinal resection, chronic diarrhea, and intestinal obstruction; 15) Meets any of the following cardiac criteria: mean corrected QT interval (QTc) from an electrocardiogram (ECG) in the resting state;470 msec (for the first anomaly, the test was retest once within 48 h, calculated based on the average result of two times).A variety of clinically significant cardiac rhythm, conduction, and resting ECG abnormalities, such as complete left bundle branch block, degree III, degree II, PR interval >250 msec.Various factors that may increase the risk of prolonged QTC or arrhythmic events, such as coronary heart disease, heart failure, hypokalemia, congenital long QT syndrome, a family history of first-degree relative with long QT syndrome or sudden unexplained death under age 40, and being on any known medication for prolonged QT; 16) Patients with any severe and/or uncontrolled disease, including but not limited to: patients with poor blood pressure control (systolic > 150 mmHg, diastolic > 100 mmHg);Suffer from myocardial ischemia or myocardial infarction, arrhythmias (including QTc ≥440ms) and congestive heart failure (New York Heart Association (NYHA) grade) of grade I or above;Active or uncontrolled severe infection (≥CTC AE grade 2 infection);Cirrhosis, decompensated liver disease;Renal failure requires hemodialysis or peritoneal dialysis;Poor diabetes control (fasting blood glucose (FBG) > 10mmol/L);Routine urine indicated urinary protein ≥++, and confirmed 24-hour urinary protein quantitative > 1.0 g; 17) Patients with epileptic seizures requiring treatment, with a history of psychotropic substance abuse and unable to quit or with mental disorders; 18) Previous history of interstitial lung disease, drug-induced interstitial lung disease, radiation pneumonia requiring steroid treatment, and clinically evidenced active interstitial lung disease; 19) thrombotic or embolic venous or arterial events, such as cerebrovascular accidents, including transient ischemic attack, arterial thrombosis, deep vein thrombosis and pulmonary embolism, occurred within 6 months before enrollment;Has a history of hemorrhagic disease or abnormal blood clotting.
20) Lactating female patients.
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:Pembrolizumab combined with Anlotinib
Anlotinib 12 mg QD p.o for 2 weeks and then stop for 1 week, combined with Pembrolizumab 200 mg iv on day 1, and every 21 days is a treatment cycle until the disease progresses or the toxicity cannot be tolerated
|
Pembrolizumab (formerly lambrolizumab, brand name Keytruda) is a humanized antibody used in cancer immunotherapy.
This includes to treat melanoma, lung cancer, head and neck cancer, Hodgkin lymphoma, an stomach cancer
他の名前:
Anlotinib is an oral small molecule multi-target receptor tyrosine kinase inhibitor
他の名前:
|
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 |
---|---|---|
objective response rates(ORR)
時間枠:1 year
|
To evaluate objective response rates of first-line Pembrolizumab combined with Anlotinib in Chinese patients with recurrent and/or metastatic head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS≥1
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1 year
|
二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
---|---|---|
disease control rate(DCR)
時間枠:3 year
|
To evaluate other efficacy indicators of first-line Pembrolizumab combined with Anlotinib in Chinese patients with recurrent and/or metastatic head and neck squamous cell carcinoma with PD-L1 CPS≥1, including disease control rate(DCR)
|
3 year
|
duration of response(DOR)
時間枠:3 year
|
To evaluate other efficacy indicators of first-line Pembrolizumab combined with Anlotinib in Chinese patients with recurrent and/or metastatic head and neck squamous cell carcinoma with PD-L1 CPS≥1, duration of response(DOR)
|
3 year
|
progression-free survival(PFS)
時間枠:3 year
|
To evaluate other efficacy indicators of first-line Pembrolizumab combined with Anlotinib in Chinese patients with recurrent and/or metastatic head and neck squamous cell carcinoma with PD-L1 CPS≥1, progression-free survival(PFS)
|
3 year
|
overall survival (OS)
時間枠:5 year
|
To evaluate other efficacy indicators of first-line Pembrolizumab combined with Anlotinib in Chinese patients with recurrent and/or metastatic head and neck squamous cell carcinoma with PD-L1 CPS≥1, overall survival (OS)
|
5 year
|
その他の成果指標
結果測定 |
メジャーの説明 |
時間枠 |
---|---|---|
tumor mutation burden(TMB)
時間枠:3 year
|
Correlation results of tumor mutation burden(TMB)
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3 year
|
T cell gene expression
時間枠:3 year
|
Correlation results of T cell gene expression
|
3 year
|
協力者と研究者
スポンサー
捜査官
- 主任研究者:Yuankai Shi, MD、Cancer Institute/Hospital, Chinese Academy of Medical Sciences&Peking Union Medical college
研究記録日
主要日程の研究
研究開始 (実際)
一次修了 (予想される)
研究の完了 (予想される)
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
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
- NCT20217
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?
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米国FDA規制医薬品の研究
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