XB2001 と ONIVYDE + 5-FU/LV (+フォリン酸) の併用による進行性膵臓がん (1-BETTER)
XB2001 (抗 IL-1⍺ 真のヒト抗体) を ONIVYDE + 5-FU/LV (+フォリン酸) と組み合わせて検討する第 I/II 相無作為化二重盲検プラセボ対照試験 (1-BETTER)膵臓癌
このトライアルには、2 つの部分 (フェーズ 1 とフェーズ 2) が含まれます。
最初の部分は、ONIVYDE + LV + 5-FU化学療法レジメンと組み合わせて、用量制限毒性（DLT）によって測定されるXB2001の最大耐用量（MTD）を確立するための第I相、非盲検、用量漸増試験です。進行膵臓癌の患者とその後の第 2 相試験の推奨用量を決定します。
フェーズ 2 の部分は、XB2001 の確立された最大許容用量 (MTD) で実施されます。 第 2 相部分の目標登録は 60 人の患者で、XB2001 と ONIVYDE + LV + 5-FU (アーム 1) またはプラセボと ONIVYDE + LV + 5-FU (アーム 2) に 1:1 で無作為化されます。
調査の概要
状態
条件
詳細な説明
研究タイトル: XB2001 (抗 IL-1⍺ 真のヒト抗体) と ONIVYDE + 5-FU/LV (+フォリン酸) 進行膵臓癌
スポンサー: XBiotech USA, Inc.
研究委員長: Benjamin Musher, M.D.
サンプルサイズ: 米国では約 69 人の患者が登録されます (非盲検第 1 相部分で少なくとも 9 人の患者、無作為化された第 2 相部分で 60 人の患者)。
おおよその所要時間:
このトライアルには 2 つのフェーズが含まれます。 最初の部分は、ONIVYDE + ロイコボリン l + d ラセミ体を投与されている転移性膵臓腺癌の少なくとも 9 人の患者における XB2001 の安全性、忍容性を評価し、最大耐量 (MTD) を確立する第 I 相、非盲検、用量漸増試験です。 + 5-フルオロウラシル化学療法による治療。 第I相部分の各患者の期間は14日間（1治療サイクル）で、ONIVYDE +ロイコボリンl + dラセミ+ 5-フルオロウラシル化学療法を受ける前にXB2001を1回静脈内投与し、投与量を評価します。限定毒性（DLT）。 フェーズ II の部分は、フェーズ I の完了と MTD の宣言に続いて実施されます。 試験の無作為化二重盲検プラセボ対照第II相部分への被験者の参加期間は約28週間で、最大30日間のスクリーニング期間と24週間の治療期間が含まれます。 すべての研究対象者は、臨床的に有益であると判断され、許容できない毒性がないと判断される限り、XB2001 による非盲検延長での治療を継続できます。
研究の種類
入学 (実際)
段階
- フェーズ2
- フェーズ 1
連絡先と場所
研究場所
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Arizona
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Tucson、Arizona、アメリカ、85711
- Arizona Oncology Associates
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California
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Burbank、California、アメリカ、91505
- Disney Family Cancer Center at Providence St. Joseph Medical Center
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Cerritos、California、アメリカ、90703
- TOI Clinical Research
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Fullerton、California、アメリカ、92835
- Providence St. Joseph Heritage - Fullerton, CA
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Newport Beach、California、アメリカ、92663
- Hoag Memorial Hospital Presbyterian
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Colorado
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Grand Junction、Colorado、アメリカ、81505
- Grand Valley Oncology
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Florida
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Lake Mary、Florida、アメリカ、32746
- Sarah Cannon - Florida Cancer Specialists
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Miami Beach、Florida、アメリカ、33140
- Mt. Sinai Comprehensive Cancer Center
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Sarasota、Florida、アメリカ、34239
- Sarasota Memorial Hospital
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Weston、Florida、アメリカ、33331
- Cleveland Clinic of Florida
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Indiana
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Goshen、Indiana、アメリカ、46526
- Goshen Center for Cancer Care
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Kansas
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Merriam、Kansas、アメリカ、66204
- Alliance for Multispecialty Research, LLC
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Louisiana
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New Orleans、Louisiana、アメリカ、70121
- Ochsner Clinic Foundation
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Michigan
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Detroit、Michigan、アメリカ、48201
- Barbara Ann Karmanos Cancer Institute
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Farmington Hills、Michigan、アメリカ、48334
- Revive Research - Farmington Hills
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Sterling Heights、Michigan、アメリカ、48126
- Revive Research - Sterling Heights
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Montana
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Billings、Montana、アメリカ、59102
- St. Vincent Frontier Cancer Center
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New Jersey
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Florham Park、New Jersey、アメリカ、07932
- Summit Medical Group
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New York
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Stony Brook、New York、アメリカ、11794
- Stony Brook Cancer Center
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The Bronx、New York、アメリカ、10461
- Montefiore Einstein Medical Center
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Oregon
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Portland、Oregon、アメリカ、97213
- Providence Portland
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Pennsylvania
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Pittsburgh、Pennsylvania、アメリカ、15232
- UPMC Hillman Cancer Center
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Tennessee
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Knoxville、Tennessee、アメリカ、37920
- University of Tennessee Medical Center Cancer Institute
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Nashville、Tennessee、アメリカ、37232
- Vanderbilt University
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Nashville、Tennessee、アメリカ、37203
- Sarah Cannon - Tennessee Oncology
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Texas
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Arlington、Texas、アメリカ、76012
- Texas Oncology - Arlington
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Dallas、Texas、アメリカ、75230
- Mary Crowley Cancer Research
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Utah
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Ogden、Utah、アメリカ、84405
- Community Cancer Trials of Utah
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Virginia
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Fairfax、Virginia、アメリカ、22031
- Virginia Cancer Specialists
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Midlothian、Virginia、アメリカ、23114
- Bon Secours St. Francis Cancer Center
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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
説明
包含基準:
- -組織学的または細胞学的に確認された、転移性、切除不能、または再発性の膵臓外分泌腺癌
- -固形腫瘍V1.1の反応評価基準による少なくとも1つの測定可能な病変
- 1回のゲムシタビンベースの治療または1回のFOLFIRINOXとゲムシタビンの併用療法後の記録された疾患進行
- -0または1のEastern Cooperative Oncology Group（ECOG）パフォーマンスまたはKarnofskyパフォーマンスステータス（KPS）≥70
- 十分な肝機能、腎機能、骨髄機能
除外基準:
- 初回投与予定日から2週間以内のパフォーマンスステータス（医療記録）の臨床的に有意な低下
- 臨床的に重要な胃腸障害
- -組み入れ前6か月未満の重度の動脈血栓塞栓性イベント
- 以前の全脳放射線療法（WBRT）
- 脳転移の証拠
- -NYHA クラス III または IV のうっ血性心不全、心室性不整脈、または制御されていない血圧 (≥ 160/100 mm Hg として定義)
- -強力なCYP3A4誘導剤または阻害剤および/またはUGT1A1阻害剤の使用は、訪問1 /ベースライン訪問の14日前まで。
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：順次割り当て
- マスキング：4倍
武器と介入
参加者グループ / アーム |
介入・治療 |
|---|---|
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実験的：Phase I: Dose Escalation Phase
In Phase I (Dose escalation phase), 3 sequential dose levels were administered by participants; 250 mg (dose cohort 1), 500 mg (dose cohort 2), and 1000 mg (dose cohort 3), and traditional 3:3 design was used. Dose-escalation will continue if none of three subjects experience a dose-limiting toxicity (DLT). After enrollment participants received two treatment cycles (a total of 28 days) in which they were given one intravenous (IV) dose of XB2001 prior to receiving ONIVYDE 70 mg/m2 IV over 90 minutes, followed by leucovorin 400 mg/m2 IV over 30 minutes, followed by 5-Fluorouracil 2400 mg/m2 intravenously over 46 hours at each cycle. |
Subjects were administered one intravenous (IV) dose of XB2001 250 mg prior to receiving ONIVYDE 70 mg/m2 IV over 90 minutes, followed by leucovorin 400 mg/m2 IV over 30 minutes, followed by 5-Fluorouracil 2400 mg/m2 intravenously over 46 hours at each cycle.
他の名前：
Subjects were administered one intravenous (IV) dose of XB2001 500 mg prior to receiving ONIVYDE 70 mg/m2 IV over 90 minutes, followed by leucovorin 400 mg/m2 IV over 30 minutes, followed by 5-Fluorouracil 2400 mg/m2 intravenously over 46 hours at each cycle.
他の名前：
Subjects were administered one intravenous (IV) dose of XB2001 1000 mg prior to receiving ONIVYDE 70 mg/m2 IV over 90 minutes, followed by leucovorin 400 mg/m2 IV over 30 minutes, followed by 5-Fluorouracil 2400 mg/m2 intravenously over 46 hours at each cycle.
他の名前：
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実験的：Phase II: Dose Expansion Phase
In Phase II (dose expansion phase), participants were randomized in 1:1 fashion and received:
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Subjects were administered one intravenous (IV) dose of XB2001 1000 mg prior to receiving ONIVYDE 70 mg/m2 IV over 90 minutes, followed by leucovorin 400 mg/m2 IV over 30 minutes, followed by 5-Fluorouracil 2400 mg/m2 intravenously over 46 hours at each cycle.
他の名前：
Subjects were administered one intravenous (IV) dose of placebo 1000 mg prior to receiving ONIVYDE 70 mg/m2 IV over 90 minutes, followed by leucovorin 400 mg/m2 IV over 30 minutes, followed by 5-Fluorouracil 2400 mg/m2 intravenously over 46 hours at each cycle.
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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 |
|---|---|---|
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To Establish the Maximum Tolerated Dose (MTD) of XB2001 as Measured by Dose-Limiting Toxicity (DLT), in Combination With ONIVYDE + LV + 5-FU Chemotherapy Regimen in Patients With Advanced Pancreatic Cancer.
時間枠：28 days (consisting of the first two 14-day treatment cycles or the formal DLT observation window).
|
The primary objective of the Phase I portion is to identify the MTD of XB2001 when administered in combination with ONIVYDE + LV + 5-FU. The MTD is defined as the highest dose level at which no more than one out of six subjects experience a DLT. If two or more subjects in a cohort of six experience a DLT, the MTD is considered exceeded, and the previous lower dose level will be identified as the MTD. If no DLTs are observed at the highest dose level studied, that dose will be used for Phase II. A DLT is defined as any Grade 3-4 adverse event (per NCI CTCAE v5.0) occurring within the first 28 days that is deemed possibly related to the combination regimen, unless the toxicity is clearly attributable to a single non-XB2001 component. Specific DLT criteria include:
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28 days (consisting of the first two 14-day treatment cycles or the formal DLT observation window).
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Safety and Tolerability of XB2001 in Combination With ONIVYDE + LV + 5-FU
時間枠：From post-infusion visit 1(week 0) through visit 13 (week 24), which is two weeks after the last infusion.
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This endpoint evaluates the cumulative safety profile and patient tolerance of XB2001 when administered at the Maximum Tolerated Dose (MTD) or the maximum dose studied in Phase I, in combination with the ONIVYDE + LV + 5-FU regimen. Safety is characterized by the total number of participants in each cohort who experienced one or more adverse events. For the purpose of this count, each participant is counted only once, regardless of the total number of individual adverse events experienced. |
From post-infusion visit 1(week 0) through visit 13 (week 24), which is two weeks after the last infusion.
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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 |
|---|---|---|
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Progression Free Survival (PFS)
時間枠：From baseline until the date of first documented disease progression or date of death (from any cause), whichever come first.
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Progression free survival (PFS) was defined as the time from randomization to first progression based on RECIST v1.1 criteria or death from any cause, whichever occurred first.
Subjects who had no baseline and post-baseline tumor assessment and no death, or no adequate post-baseline tumor assessment and no death were censored at the date of randomization.
Subjects alive and without documented disease progression at the time of data analysis are censored at the date of the last adequate tumor assessment.
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From baseline until the date of first documented disease progression or date of death (from any cause), whichever come first.
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Overall Survival (OS)
時間枠：From baseline until death from any cause
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OS was defined as the duration from the date of randomization until death irrespective of the cause.
Subjects who were alive at the time of analysis were censored at the last known date alive.
Subjects without any data after baseline were censored on the randomization day.
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From baseline until death from any cause
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Objective Response Rate (ORR)
時間枠：Analyses performed at Visit 5 (Week 8), Visit 9 (Week 16), and Visit 13 (Week 24). This outcome measure was reported for Visit 13.
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Objective Response Rate (ORR) is defined as the proportion of subjects in the Phase II Population who achieved a Best Overall Response (BOR) of either Complete Response (CR) or Partial Response (PR), as defined by RECIST v1.1 criteria.
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Analyses performed at Visit 5 (Week 8), Visit 9 (Week 16), and Visit 13 (Week 24). This outcome measure was reported for Visit 13.
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Time to Treatment Failure(TTF)
時間枠：From baseline until treatment failure assessed up to Visit 13 (Week 24)
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TTF measures the time from randomization to discontinuation of treatment for any reason, including, but not limited to, disease progression, treatment-related toxicity, and/or death during study.
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From baseline until treatment failure assessed up to Visit 13 (Week 24)
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Number of Serious Adverse Events (SAEs)
時間枠：From post-infusion visit 1(week 0) through visit 13 (week 24), which is two weeks after the last infusion.
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This outcome measure calculates the total number of unique participants who reported serious adverse events (SAEs) in each group.
An SAE is defined as any untoward medical occurrence that results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, or is a congenital anomaly/birth defect.
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From post-infusion visit 1(week 0) through visit 13 (week 24), which is two weeks after the last infusion.
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Incidence of Grade 3-4 Diarrhea
時間枠：From post-infusion visit 1(week 0) through visit 13 (week 24), which is two weeks after the last infusion.
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This measure tracks the overall burden of severe (Grade 3) or life-threatening (Grade 4) diarrhea as defined by the NCI CTCAE v5.0.
Grade 3 events are severe enough to require medical intervention or significantly limit a person's ability to care for themselves, while Grade 4 events represent urgent, life-threatening clinical situations.
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From post-infusion visit 1(week 0) through visit 13 (week 24), which is two weeks after the last infusion.
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Duration of Hospitalization
時間枠：From post-infusion visit 1(week 0) through visit 13 (week 24), which is two weeks after the last infusion.
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This outcome measure calculates the sum of duration of hospitalizations during the study period in phase II population for both groups.
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From post-infusion visit 1(week 0) through visit 13 (week 24), which is two weeks after the last infusion.
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Plasma Concentration of Natrunix
時間枠：Reported results Natrunix: Phase I: V1 post-dose collected at 30 min post-infusion at visit 1(Week 0), which represents Cmax of Cycle 1. Phase II: V6 pre-dose, at Visit 6 (Week 10), represents the trough of steady state concentration.
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Measurement of the concentration of Natrunix in plasma samples to evaluate the pharmacokinetic profile. Due to reporting limitations on this portal, results from only one time point are reported here. For Phase 1, samples were collected at V1 pre-dose, V1 post-dose, V2 pre-dose, V3 follow up. For phase 2, samples were collected at V1 pre-dose, V1 post-dose, V1 Day 4, V1 Day 7, V2 pre-dose, V3 pre-dose, V4 pre-dose, V6 pre-dose, V8 pre-dose, and V13 follow up. Placebo patients were tested at V1 post-dose only for verification. |
Reported results Natrunix: Phase I: V1 post-dose collected at 30 min post-infusion at visit 1(Week 0), which represents Cmax of Cycle 1. Phase II: V6 pre-dose, at Visit 6 (Week 10), represents the trough of steady state concentration.
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Number of Treatment Cycles
時間枠：From randomization to end of study or study discontinuation for any reasons, up to 24 weeks
|
This measures the total number of cycles (total number of doses) received by subjects after randomization in each arm.
|
From randomization to end of study or study discontinuation for any reasons, up to 24 weeks
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その他の成果指標
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
症状アンケートの結果は、注入後のさまざまな時点で治療群ごとに要約され、経時的に比較されます
時間枠：22週間まで評価された注入後のさまざまな時点で
|
スコアの範囲は 12 ～ 48 です。
高いスコアは悪い結果を表します。
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22週間まで評価された注入後のさまざまな時点で
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必要な心電図の数によって測定された心毒性と、治療群ごとに要約され、経時的に比較された心毒性関連イベント
時間枠：経時的に比較し、22 週間まで評価
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探索的エンドポイント (フェーズ 2 部分のみ)
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経時的に比較し、22 週間まで評価
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協力者と研究者
スポンサー
捜査官
- スタディチェア：David J Park、Providence St. Joseph Heritage
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。