Molecularly Stratified Trial for Newly Diagnosed Infant-Type Hemispheric Glioma
A Molecularly Stratified Phase II Trial for Newly Diagnosed Infant-Type Hemispheric Glioma (IHG)
The purpose of this study is to test whether giving treatment before surgery helps babies who are newly diagnosed with Infant-Type Hemispheric Glioma (IHG) have safer and better surgery results.
調査の概要
状態
詳細な説明
Primary Objective
- To estimate the complete tumor response rate (CTR) associated with molecularly directed neoadjuvant treatment (entrectinib for NTRK1/2/3 and ROS1, alectinib for ALK, and chemotherapy for tumors with other fusions and no fusions). (Strata A, B, and C)
- To estimate the safe surgical resection rate associated with molecular-directed neo-adjuvant treatment entrectinib for NTRK1/2/3 and ROS1, alectinib for ALK, and chemotherapy for tumors with other fusions and no fusions. (Strata A, B, and C)
Secondary Objectives
- To estimate the stratum-specific and study-wide event-free survival (EFS) and overall survival (OS) for patients enrolled in SJIHG25 (Strata A, B, C, and D)
- To estimate the change in neurodevelopment and cognitive performance pre- and post-primary surgery in infants with newly diagnosed IHG treated with molecularly directed neoadjuvant treatment. (Strata A, B, and C)
This is a phase II clinical trial evaluating the use of molecularly directed neoadjuvant treatment for patients with newly diagnosed Infant-Type Hemispheric Glioma (IHG) to improve surgical outcome (efficacy and safety).
Bridge Therapy is recommended for participants who are being screened (participants who have signed the screening consent) for the following reasons:
- Participant can be enrolled on the stratum bridge and 1-4 courses of cytotoxic chemotherapy CCE (carboplatin IV day 2, cyclophosphamide IV day1, and etoposide IV days 1 and 2), which may be given prior to surgical intervention to stabilize the patient. Each cycle of CCE treatment cycle is approximately 28 days in length.
- If the waiting period for diagnostic work-up is deemed unsafe for clinical reasons, the participant may enroll in the stratum bridge and receive one course of bridge chemotherapy with CCE before enrollment to stratum A, B, or C.
- Where a molecular target has been identified prior to screening and confirmation of diagnosis by central pathology review, the participant can be enrolled on stratum bridge and started on treatment based on the molecular target (alectinib po day1-28, entrectinib po day1-28, or chemotherapy (CCE), with pending central pathology review, if waiting for completion of the central pathology review is deemed to put the patient at increased risk of tumor progression.
Decisions regarding bridge therapy need to be discussed and approved by the study PI/team before starting treatment.
Enrollment in strata A, B, C, and D can occur only after central pathology review at St. Jude Children's Research Hospital confirms the diagnosis. Participants will be assigned to treatment strata based on whether residual tumor is present and types of RTK fusion.
Participants with ALK fusion will receive alectinib as neoadjuvant treatment (Stratum A), participants with NTRK 1/2/3 or ROS1 fusions will receive entrectinib as neoadjuvant treatment (Stratum B), and participants with no RTK fusion or RTK fusions other than ALK, ROS1 or NTRK1/2/3 (including MET fusion) will receive chemotherapy with carboplatin, etoposide, and cyclophosphamide as neoadjuvant treatment (Stratum C). Post primary surgery all participants on Strata A, B and C will be treated with 4 courses (1 course = 28 days) of adjuvant chemotherapy with carboplatin, etoposide, and cyclophosphamide.
The participants who have no residual disease at the time of enrollment will be treated with 4 courses (1 course = 28 days) of adjuvant chemotherapy with carboplatin, etoposide, and cyclophosphamide on stratum D.
Participants will be followed for five years following enrollment.
研究の種類
入学 (推定)
段階
- フェーズ2
連絡先と場所
研究連絡先
- 名前：Tabatha E. Doyle, RN
- 電話番号：901-595-2544
- メール：tabatha.doyle@stjude.org
研究場所
-
-
Tennessee
-
Memphis、Tennessee、アメリカ、38105
- St. Jude Children's Research Hospital
-
コンタクト：
- Tabatha E. Doyle, RN
- 電話番号：901-595-2544
- メール：tabatha.doyle@stjude.org
-
主任研究者：
- Aditi Bagchi, M.D., Ph.D.
-
-
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: Screening
- Patient with presumptive or suspected (new) diagnosis of Infant-Type Hemispheric Glioma (IHG)
- Patient age at diagnosis is from birth to ≤ 60 months
- Patient has MRI/CT scan imaging of a supra-tentorial, hemispheric tumor avail-able for review before screening consent.
- Patient is willing to undergo a biopsy procedure to confirm tissue diagnosis.
- Adequate tumor tissue for central review of pathology, at the St. Jude Children's Research Hospital, DNA methylation array analysis, and NGS testing should be provided, if available from previous surgery, but is not required for screening eligibility.
- The parent or legal guardian of the patient should be able to understand and be willing to sign a written informed consent document according to institutional guidelines
Inclusion Criteria: Enrollment
-
Without a central pathology confirmed diagnosis of IHG
-
Stratum-Bridge
- The patient should meet all screening criteria and should have signed the screening consent.
- Meets one of the exception/modification criteria
-
-
Centrally confirmed diagnosis of IHG
-
Strata A and B
- The tumor has confirmed in-frame gene fusions involving ALK (Stratum A)
- The tumor has confirmed in-frame gene fusions involving NTRK1/2/3 or ROS1 (Stratum B).
- A measurable primary residual tumor at the time of enrollment
-
Stratum C
- Central pathology review doesn't detect in-frame gene fusion involving ALK, NTRK 1/2/3, or ROS1in the tumor
- Central pathology review confirms the presence of in-frame MET gene fusion or any other in frame fusion other than those involving ALK, NTRK1/2/3, or ROS1 gene fusions
- A measurable primary residual tumor at the time of enrollment
-
Stratum D
- No measurable primary residual tumor at the time of enrollment
-
Exclusion Criteria: (All Strata)
- Age > 60 months
- Any prior cancer-directed therapy
- Organ Dysfunction, or a medical condition that, in the principal investigator's judgment, could compromise their ability to tolerate or absorb protocol therapy or would interfere with study procedures and results.
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：非ランダム化
- 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：Stratum A
|
By mouth, nasogastric, or gastronomy/stomach tube, Day 1-28
他の名前：
Primary surgery (Strata A, B, and C) post Neoadjuvant therapy with a goal of attaining gross total (GTR) or near total resection (NTR) of the tumor.
他の名前：
IV (intravenous) day 1
他の名前：
IV (intravenous) days 1 and 2
他の名前：
IV (intravenous) day 2
他の名前：
Subcutaneous (under the skin) or IV (intravenous) day 3
他の名前：
Subcutaneous (under the skin) day 3
他の名前：
|
|
実験的：Stratum B
|
Primary surgery (Strata A, B, and C) post Neoadjuvant therapy with a goal of attaining gross total (GTR) or near total resection (NTR) of the tumor.
他の名前：
IV (intravenous) day 1
他の名前：
IV (intravenous) days 1 and 2
他の名前：
IV (intravenous) day 2
他の名前：
Subcutaneous (under the skin) or IV (intravenous) day 3
他の名前：
Subcutaneous (under the skin) day 3
他の名前：
By mouth, nasogastric, or gastronomy/stomach tube, Day 1-28
他の名前：
|
|
実験的：Stratum C
|
Primary surgery (Strata A, B, and C) post Neoadjuvant therapy with a goal of attaining gross total (GTR) or near total resection (NTR) of the tumor.
他の名前：
IV (intravenous) day 1
他の名前：
IV (intravenous) days 1 and 2
他の名前：
IV (intravenous) day 2
他の名前：
Subcutaneous (under the skin) day 3
他の名前：
|
|
実験的：Stratum D
Participants who have no measurable residual disease at the time of enrollment.
|
IV (intravenous) day 1
他の名前：
IV (intravenous) days 1 and 2
他の名前：
IV (intravenous) day 2
他の名前：
Subcutaneous (under the skin) or IV (intravenous) day 3
他の名前：
Subcutaneous (under the skin) day 3
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 |
|---|---|---|
|
Rate of Complete Tumor Response (CTR) among patients in Strata A, B, and C
時間枠：approximately 4 months after enrollment
|
The proportion of patients whose extent of tumor resection meets criteria for gross total / near total resection (GTR/NTR) after neoadjuvant therapy and surgery. |
approximately 4 months after enrollment
|
|
Rate of safe surgical resection among patients in Strata A, B, and C
時間枠：Up to 72 hours after surgery
|
Proportion of patients whose surgery is completed without clinically significant intra-operative blood loss/hemorrhage. Success for this outcome measure will include surgery without any of the following: (i) Initiation of massive transfusion protocol- i.e., requiring more than one volume (80ml/Kg) of transfusion over a period of 24 hours (ii) Hemorrhage leading to cessation of surgery (iii) Hemorrhagic complications leading to second neurosurgery within 72 hours of the first surgery. |
Up to 72 hours after surgery
|
二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Event free survival (EFS)
時間枠：2 years
|
EFS is defined as time from enrollment for treatment (including bridge therapy) until progression, subsequent malignancy or death for any reason or until last follow-up, whichever is earlier. |
2 years
|
|
Overall survival (OS)
時間枠：2 years
|
OS is defined as time from enrollment for treatment (including bridge therapy) until death for any reason or until last follow-up, whichever is earlier. |
2 years
|
|
Change in neurodevelopment and cognitive performance pre- and post-primary surgery in infants with newly diagnosed IHG treated with molecularly directed neoadjuvant treatment: BSID-4
時間枠：Pre-surgery/baseline and after the intervention/procedure/primary surgery for up to 12 weeks
|
Pre-surgery/baseline and after the intervention/procedure/primary surgery for up to 12 weeks
|
|
|
Change in neurodevelopment and cognitive performance pre- and post-primary surgery in infants with newly diagnosed IHG treated with molecularly directed neoadjuvant treatment: NIH Baby Toolbox
時間枠：Pre-surgery/baseline and after the intervention/procedure/primary surgery for up to 12 weeks
|
Pre-surgery/baseline and after the intervention/procedure/primary surgery for up to 12 weeks
|
協力者と研究者
捜査官
- 主任研究者：Aditi Bagchi, M.D., Ph.D.、St. Jude Children's Research Hospital
出版物と役立つリンク
研究記録日
主要日程の研究
研究開始 (推定)
一次修了 (推定)
研究の完了 (推定)
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
キーワード
- 手術
- 脳腫瘍
- 新たに診断された
- 補助療法
- ネオアジュバント治療
- Infant-Type Hemispheric Glioma
- Molecularly Stratified
- Gene fusions involving ALK
- Gene fusions involving NTRK1/2/3
- Gene fusions involving ROS1
- In-frame MET gene fusion or any other in frame fusion
- Measurable primary residual tumor
- No measurable primary residual tumor
- Supra-tentorial, hemispheric tumor
追加の関連 MeSH 用語
- 脳疾患
- 中枢神経系疾患
- 神経系疾患
- 部位別新生物
- 新生物
- 神経系腫瘍
- 中枢神経系腫瘍
- 脳腫瘍
- ペプチド
- アミノ酸、ペプチド、およびタンパク質
- タンパク質
- 有機化学物質
- 炭化水素
- 炭化水素、周期的
- 生物学的要因
- 炭水化物
- ポドフィロトキシン
- テトラヒドロノフタレン
- ナフタレン
- 多環芳香族炭化水素
- 炭化水素、芳香
- 多環式化合物
- グルコシド
- グリコシド
- 調整錯体
- ホスホルアミドマスタード
- 窒素マスタード化合物
- マスタード化合物
- 炭化水素、ハロゲン化
- ホスホラミド
- 有機リン化合物
- 細胞間シグナル伝達ペプチドとタンパク質
- 糖タンパク質
- グリココンジュゲート
- コロニー刺激因子
- 造血細胞成長因子
- サイトカイン
- シクロホスファミド
- エトポシド
- カルボプラチン
- 外科的処置、手術
- 顆粒球コロニー刺激因子
- Filgrastim
- Entrectinib
- Pegfilgrastim
- アレクチニブ
その他の研究ID番号
- SJIHG25
- NCI-2026-07231 (レジストリ識別子：NCI Clinical Trial Registration Program)
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?
IPD プランの説明
Individual participant de-identified datasets containing the variables analyzed in the published article will be made available (related to the study primary or secondary objectives contained in the publication). Supporting documents such as the protocol, statistical analyses plan, and informed consent are available through the CTG website for the specific study. Data used to generate the published article will be made available at the time of article publication. Investigators who seek access to individual level de-identified data will contact the computing team in the Department of Biostatistics (ClinTrialDataRequest@stjude.org) who will respond to the data request.
IPD 共有時間枠
Data will be made available at the time of article publication.
IPD 共有アクセス基準
Data will be provided to researchers following a formal request with the following information: full name of requestor, affiliation, data set requested, and timing of when data is needed. As an informational point, the lead statistician and study principal investigator will be informed that primary results datasets have been requested.
IPD 共有サポート情報タイプ
- STUDY_PROTOCOL
- SAP
- ICF
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
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