PD-1 Blockade and Bevacizumab Replace Cisplatin in Locoregionally Advanced Nasopharyngeal Carcinoma
PD-1 Inhibitor and Bevacizumab Replace Cisplatin in Induction, Concurrent, and/or Adjuvant Therapy for High-risk Locoregionally Advanced Nasopharyngeal Carcinoma.
調査の概要
状態
条件
詳細な説明
研究の種類
入学 (予想される)
段階
- フェーズ2
- フェーズ 1
連絡先と場所
研究連絡先
- 名前:Xi Ding, MD
- 電話番号:86-19880836260
- メール:dingxi@sysucc.org.cn
研究場所
-
-
Guangdong
-
Guangzhou、Guangdong、中国、510060
- Department of Nasopharyngeal Carcinoma, Sun Yat-sen University Cancer Center
-
コンタクト:
- Ming-Yuan Chen, MD,PhD
- 電話番号:86-20-8734-2422
- メール:chenmy@sysucc.org.cn
-
-
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:
- Voluntary participation with Written informed consent.
- Age ≥ 18 years and ≤ 65 years.
- Histologically confirmed with Nonkeratinizing carcinoma of the nasopharynx (differentiated or undifferentiated type).
- Original clinical staged as III-IVa (according to the 8th AJCC edition).
- Stage III patients should meet the criteria of EBV DNA≥4000 cps/ml.
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1.
Patients must have adequate organ function:
- White blood cell count (WBC)≥4.0×109 /L, Hemoglobin ≥ 90g/L, Platelet count ≥100×109/L.
- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5×upper limit of normal (ULN),serum total bilirubin (TBIL) ≤2.0 times the upper limit of normal (ULN) .
- Adequate renal function: creatinine clearance rate≥60 ml/min or Creatinine ≤1.5× upper limit of normal value.
- INR, APTT≤1.5 x ULN.
Exclusion Criteria:
- Subjects with recurrent or metastatic nasopharyngeal carcinoma.
- Histologically or cytologically confirmed with keratinizing squamous cell carcinoma of the nasopharynx.
- Prior therapy with systemic therapy for nasopharyngeal carcinoma.
- Prior exposure to immune checkpoint inhibitors,including anti-PD-1, anti-PD-L1, anti-CTLA-4 antibodies.
- Prior exposure to antiangiogenic agents.
- Tumor invasion to the intracranial with clinical symptoms accompanied by cerebral edema, requiring hormone therapy.
- Any grade ≥2 bleeding event (according to CTCAE 5.0) occurred within 4 weeks prior to enrollment.
- Subjects with an active, known or suspected autoimmune disease.
- Subjects with clinically significant cardiovascular and cerebrovascular diseases.
- Subjects with high blood pressure who cannot be controlled well with antihypertensive drugs.
- Subjects with previous digestive tract bleeding history within 3 months or evident gastrointestinal bleeding tendency.
- Subjects with arterial / venous thrombosis events occurred within 6 months of the first dose.
- Women in the period of pregnancy, lactation, or reproductive without effective contraceptive measures.
- Seropositivity for human immunodeficiency virus (HIV).
- Known history of other malignancies (except cured basal cell carcinoma or carcinoma in situ of the cervix).
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:ランダム化
- 介入モデル:並列代入
- 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:low risk
Patients will receive induction therapy with toripalimab plus bevacizumab and gemcitabine every 3 weeks for 3 cycles before radiotherapy, then followed by IMRT and concurrent therapy with toripalimab plus bevacizumab for 2 cycles, then followed by adjuvant therapy with toripalimab every 3 weeks for a maximum of 1 year after radiotherapy.
|
Induction therapy: Toripalimab (240mg iv drip)+Bevacizumab (7.5mg/kg iv drip)+gemcitabine (1,000 mg/m2), every 3 weeks for 3 cycles before radiotherapy. Concurrent therapy: Toripalimab (240mg iv drip)+Bevacizumab (7.5mg/kg iv drip), every 3 weeks for 2 cycles during radiotherapy. Adjuvant therapy: Toripalimab (240mg iv drip), every 3 weeks for 1 year after radiotherapy. Radiation: Intensity-modulated radiotherapy. |
実験的:high risk
Patients will receive induction therapy with toripalimab plus bevacizumab and gemcitabine every 3 weeks for 3 cycles before radiotherapy, then followed by IMRT and concurrent therapy with toripalimab plus bevacizumab for 2 cycles, then followed by adjuvant therapy with toripalimab and bevacizumab every 3 weeks for a maximum of 1 year after radiotherapy.
|
Induction therapy: Toripalimab (240mg iv drip)+Bevacizumab (7.5mg/kg iv drip)+gemcitabine (1,000 mg/m2), every 3 weeks for 3 cycles before radiotherapy. Concurrent therapy: Toripalimab (240mg iv drip)+Bevacizumab (7.5mg/kg iv drip), every 3 weeks for 2 cycles during radiotherapy. Adjuvant therapy: Toripalimab (240mg iv drip)+Bevacizumab (7.5mg/kg iv drip), every 3 weeks for 1 year after radiotherapy. Radiation: Intensity-modulated radiotherapy. |
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 |
---|---|---|
grade ≥3 nasopharyngeal necrosis or hemorrhage
時間枠:At the end of each cycle (each cycle is 21 days)
|
Incidence of nasopharyngeal necrosis or massive hemorrhage (grade ≥3). Grade ≥3 hemorrhage: Grade 3, Transfusion indicated; invasive intervention indicated; hospitalization. Grade 4, Life-threatening consequences; urgent intervention indicated (e.g., tracheotomy or intubation). Grade 5, death. Grade ≥3 nasopharyngeal necrosis: Grade 3, Severe pain; unable to adequately aliment or hydrate orally; limiting self care ADL. Grade 4, Life-threatening consequences; urgent intervention indicated. Grade 5, death. |
At the end of each cycle (each cycle is 21 days)
|
二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
---|---|---|
Objective response rate
時間枠:3 weeks after indution therapy; 3 months after concurrent therapy
|
The proportion of patients whose tumors shrink to a certain size and maintain such size for a certain period of time, including patients with complete response (CR) and partial response (PR).
|
3 weeks after indution therapy; 3 months after concurrent therapy
|
Progression-free survival
時間枠:3 year
|
Progress-free survival is calculated from the date of enrollment to the date of the first progression at any site or death from any cause or censored at the date of the last follow-up.
|
3 year
|
Overall survival
時間枠:3 year
|
Overall survival is calculated from the date of enrollment to the date of the death from any cause or censored at the date of the last follow-up.
|
3 year
|
Locoregional failure-free survival (LRRFS)
時間枠:3 year
|
Defined as the time from registration to local or regional relapse, or death from any cause.
|
3 year
|
Distant metastasis-free survival (DMFS)
時間枠:3 year
|
Defined as the time from registration to distant metastasis, or death from any cause.
|
3 year
|
Incidence rate of adverse events (AEs)
時間枠:3 year
|
Analysis of acute and late adverse events (AEs) are evaluated.
Numbers of patients of treatment-related adverse events (acute toxicity) and late radiation toxicities were assessed by CTCAE v5.0.
|
3 year
|
協力者と研究者
研究記録日
主要日程の研究
研究開始 (予想される)
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
- SYSUCC-CMY-2022-0416
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
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。