Nivolumab and Bevacizumab in Patients With Advanced and or Metastatic Hepatocellular Carcinoma (NUANCE)
A Phase I Open Label Trial of a Combination of Nivolumab and Bevacizumab in Patients With Advanced and or Metastatic Hepatocellular Carcinoma
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
-
-
Utah
-
Salt Lake City、Utah、アメリカ、84112
- Huntsman Cancer Institute
-
-
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:
- Confirmed unresectable or metastatic hepatocellular carcinoma. Confirmation either by histologic confirmation or accepted radiographic criteria.
- Received at least one line of therapy with a TKI (including, but not limited to sorafenib, lenvatinib, and/or regorafenib) with evidence of disease progression clinically or radiographically as deemed by investigator, or refused therapy with a TKI. No more than two lines of prior therapy are allowed.
- Measurable disease per RECIST1.1.
- Age ≥18 years.
- ECOG performance status of 0 to 1.
- Life expectancy ≥ 12 weeks.
- Childs Pugh A (5-6 points). Demonstrate adequate organ function as defined in the table below
Hematologic:
Absolute neutrophil count (ANC) ≥ 1.5 k/µL. Platelets ≥ 100 k/µL Hemoglobin ≥ 9 g/dL
Renal:
Creatinine < 2 × ULN OR
- Able to provide informed consent and willing to sign an approved consent form that conforms to federal and institutional guidelines.
Exclusion Criteria:
- Prior treatment with anti-PD1 or anti-PD-L1 antibody therapy.
- Subjects with a prior history of DVT/PE, who have not been on stable doses of anticoagulation with low molecular weight heparin or oral anticoagulant for at least two weeks.
- History of arterial thromboembolic event in past 6 months (including CVA, MI).
- Systemic anti-cancer treatment within 2 weeks, all ongoing adverse events related to previous systemic anti-cancer therapy resolved to grade ≤1.
- Radiotherapy within 2 weeks of first dose of study medications.
- Major surgery within 6 weeks of first dose of study medications. Minor procedures (e.g. port placement, endoscopy with intervention) within 4 weeks of first dose of study medications.
- Presence of ≥ CTCAE grade 2 toxicity due to prior cancer therapy (except alopecia, peripheral neuropathy which are excluded if ≥ CTCAE grade 3).
- Medical condition that requires chronic systemic steroid therapy, or any other form of immunosuppressive medication.
- Active ongoing infection requiring therapy.
- Active HIV infection.
- History of severe hypersensitivity reaction to another monoclonal antibody.
- Active central nervous system metastases and/or carcinomatous meningitis (stable treated brain metastases not requiring steroids >4 weeks allowed).
- Cardiac conditions: class 3-4 New York Heart Association congestive heart failure, known baseline LVEF < 50%, transmural myocardial infarction, uncontrolled hypertension, angina pectoris requiring medication, clinically significant valvular disease, high-risk arrhythmia in the past 12 months.
- Any history of autoimmune disease requiring treatment in the past 5 years or felt to be at risk to reactivate autoimmune disease. Patients who are felt to no longer be at risk of activating a known autoimmune disease (e.g. type 1 diabetes, ulcerative colitis s/p complete colectomy, autoimmune thyroiditis s/p thyroidectomy or medical ablation, etc.) may be allowed to participate after discussion with the PI
- Pregnant, breast feeding, or planning to become pregnant.
- Women of childbearing potential (WOCBP) must agree to follow instructions for method(s) of contraception for the duration of study treatment with nivolumab and 5 months after the last dose of study treatment i.e., 30 days (duration of ovulatory cycle) plus the time required for the investigational drug to undergo approximately five half-lives. Contraception as described in section 7.3
- Males who are sexually active with WOCBP must agree to follow instructions for method(s) of contraception for the duration of study treatment with nivolumab and 7 months after the last dose of study treatment i.e., 90 days (duration of sperm turnover) plus the time required for the investigational drug to undergo approximately five half-lives. Contraception as described in section 7.3
- Received any live vaccine within the last 30 days.
- Other malignancy requiring treatment in the prior 2 years with the exception of locally treated squamous or basal cell carcinoma.
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:Nivolumab and bevacizumab, all patients
|
Nivolumab will be administered as a 240mg IV infusion given once every two weeks (+/- 3 days). Subjects will remain on study treatment for up to two years or until progression or excessive toxicity
他の名前:
Bevacizumab will be administered as an IV infusion from 1-10mg/kg in accordance with the appropriate subject cohort being examined as described below: Dose level 1: 5 mg/kg intravenously once every two weeks Dose level 2: 10 mg/kg intravenously once every two weeks Dose level -1: 1 mg/kg intravenously once every two weeks Dosing is based on actual body weight. There is no dose adjustment for obese or frail individuals. Dosing is recalculated if patient weight changes by more than 10% as reviewed by the principal investigator. Subjects will remain on study treatment for up to two years or until progression or excessive toxicity |
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 |
---|---|---|
Adverse Events that occur
時間枠:Every 14 day cycle for up to 2 years - Patients are expected to be on treatment for an average of 6 months
|
Investigate the safety and tolerability of 14-day cycles of nivolumab plus bevacizumab. Adverse events will be collected for each subject that received the study treatment combination. |
Every 14 day cycle for up to 2 years - Patients are expected to be on treatment for an average of 6 months
|
Determine the maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D)
時間枠:The DLT period will begin at Cycle 1 Day 1 and continue through Cycle 1 Day 28 for each patient
|
Determine the maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D). Dose Limiting Toxicities (DLT) will define subsequent subject accrual and dose escalation |
The DLT period will begin at Cycle 1 Day 1 and continue through Cycle 1 Day 28 for each patient
|
二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
---|---|---|
Progression Free Survival (PFS)
時間枠:3 years after treatment stops
|
To examine the effect of the study treatment combination on the rate of progression-free survival (PFS). Subjects will have regular imaging scans to measure disease status and response will be defined by RECIST1.1. |
3 years after treatment stops
|
Overall Survival
時間枠:3 years after treatment stops
|
To examine the effect of the study treatment combination on the rate of overall survival.
|
3 years after treatment stops
|
協力者と研究者
スポンサー
捜査官
- 主任研究者:Glynn W Gilcrease, MD、University of Utah
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。
Nivolumabの臨床試験
-
Yonsei University募集
-
Roswell Park Cancer InstituteNational Cancer Institute (NCI)募集
-
Alliance for Clinical Trials in OncologyNational Cancer Institute (NCI)募集