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.
Přehled studie
Postavení
Podmínky
Detailní popis
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.
Typ studie
Zápis (Odhadovaný)
Fáze
- Fáze 2
Kontakty a umístění
Studijní kontakt
- Jméno: Tabatha E. Doyle, RN
- Telefonní číslo: 901-595-2544
- E-mail: tabatha.doyle@stjude.org
Studijní místa
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Tennessee
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Memphis, Tennessee, Spojené státy, 38105
- St. Jude Children's Research Hospital
-
Kontakt:
- Tabatha E. Doyle, RN
- Telefonní číslo: 901-595-2544
- E-mail: tabatha.doyle@stjude.org
-
Vrchní vyšetřovatel:
- Aditi Bagchi, M.D., Ph.D.
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-
Kritéria účasti
Kritéria způsobilosti
Věk způsobilý ke studiu
Přijímá zdravé dobrovolníky
Pohlaví způsobilá ke studiu
Popis
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
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Stratum-Bridge
- The patient should meet all screening criteria and should have signed the screening consent.
- Meets one of the exception/modification criteria
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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
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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.
Studijní plán
Jak je studie koncipována?
Detaily designu
- Primární účel: Léčba
- Přidělení: Nerandomizované
- Intervenční model: Paralelní přiřazení
- Maskování: Žádné (otevřený štítek)
Zbraně a zásahy
Skupina účastníků / Arm |
Intervence / Léčba |
|---|---|
|
Experimentální: Stratum A
|
By mouth, nasogastric, or gastronomy/stomach tube, Day 1-28
Ostatní jména:
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.
Ostatní jména:
IV (intravenous) day 1
Ostatní jména:
IV (intravenous) days 1 and 2
Ostatní jména:
IV (intravenous) day 2
Ostatní jména:
Subcutaneous (under the skin) or IV (intravenous) day 3
Ostatní jména:
Subcutaneous (under the skin) day 3
Ostatní jména:
|
|
Experimentální: 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.
Ostatní jména:
IV (intravenous) day 1
Ostatní jména:
IV (intravenous) days 1 and 2
Ostatní jména:
IV (intravenous) day 2
Ostatní jména:
Subcutaneous (under the skin) or IV (intravenous) day 3
Ostatní jména:
Subcutaneous (under the skin) day 3
Ostatní jména:
By mouth, nasogastric, or gastronomy/stomach tube, Day 1-28
Ostatní jména:
|
|
Experimentální: 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.
Ostatní jména:
IV (intravenous) day 1
Ostatní jména:
IV (intravenous) days 1 and 2
Ostatní jména:
IV (intravenous) day 2
Ostatní jména:
Subcutaneous (under the skin) day 3
Ostatní jména:
|
|
Experimentální: Stratum D
Participants who have no measurable residual disease at the time of enrollment.
|
IV (intravenous) day 1
Ostatní jména:
IV (intravenous) days 1 and 2
Ostatní jména:
IV (intravenous) day 2
Ostatní jména:
Subcutaneous (under the skin) or IV (intravenous) day 3
Ostatní jména:
Subcutaneous (under the skin) day 3
Ostatní jména:
|
Co je měření studie?
Primární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
|
Rate of Complete Tumor Response (CTR) among patients in Strata A, B, and C
Časové okno: approximately 4 months after enrollment
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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
Časové okno: Up to 72 hours after surgery
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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
|
Sekundární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
|
Event free survival (EFS)
Časové okno: 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
|
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Overall survival (OS)
Časové okno: 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
Časové okno: Pre-surgery/baseline and after the intervention/procedure/primary surgery for up to 12 weeks
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Pre-surgery/baseline and after the intervention/procedure/primary surgery for up to 12 weeks
|
|
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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
Časové okno: 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
|
Spolupracovníci a vyšetřovatelé
Vyšetřovatelé
- Vrchní vyšetřovatel: Aditi Bagchi, M.D., Ph.D., St. Jude Children's Research Hospital
Publikace a užitečné odkazy
Termíny studijních záznamů
Hlavní termíny studia
Začátek studia (Odhadovaný)
Primární dokončení (Odhadovaný)
Dokončení studie (Odhadovaný)
Termíny zápisu do studia
První předloženo
První předloženo, které splnilo kritéria kontroly kvality
První zveřejněno (Aktuální)
Aktualizace studijních záznamů
Poslední zveřejněná aktualizace (Aktuální)
Odeslaná poslední aktualizace, která splnila kritéria kontroly kvality
Naposledy ověřeno
Více informací
Termíny související s touto studií
Klíčová slova
- Chirurgická operace
- Mozkový nádor
- Nově diagnostikováno
- Adjuvantní léčba
- Neoadjuvantní léčba
- 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
Další relevantní podmínky MeSH
- Onemocnění mozku
- Onemocnění centrálního nervového systému
- Nemoci nervového systému
- Novotvary podle místa
- Novotvary
- Novotvary nervového systému
- Novotvary centrálního nervového systému
- Novotvary mozku
- Peptidy
- Aminokyseliny, peptidy a proteiny
- Proteiny
- Organické chemikálie
- Uhlovodíky
- Uhlovodíky, cyklické
- Biologické faktory
- Uhlohydráty
- Podophyllotoxin
- Tetrahydronaftalenes
- Naftalenes
- Polycyklické aromatické uhlovodíky
- Uhlovodíky, aromatické
- Polycyklické sloučeniny
- Glukosidy
- Glykosidy
- Koordinační komplexy
- Fosforamidové hořčice
- Sloučeniny hořčice dusíku
- Hořčičné sloučeniny
- Uhlovodíky, halogenované
- Fosforamidy
- Organofosforové sloučeniny
- Mezibuněčné signalizační peptidy a proteiny
- Glykoproteiny
- Glykokonjugáty
- Faktory stimulující kolonie
- Růstové faktory hematopoetických buněk
- Cytokiny
- Cyklofosfamid
- Etoposid
- Karboplatina
- Chirurgické postupy, operativní
- Faktor stimulující kolonie granulocytů
- Filgrastim
- Entrectinib
- Pegfilgrastim
- Alektinib
Další identifikační čísla studie
- SJIHG25
- NCI-2026-07231 (Identifikátor registru: NCI Clinical Trial Registration Program)
Plán pro data jednotlivých účastníků (IPD)
Plánujete sdílet data jednotlivých účastníků (IPD)?
Popis plánu IPD
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.
Časový rámec sdílení IPD
Data will be made available at the time of article publication.
Kritéria přístupu pro sdílení IPD
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.
Typ podpůrných informací pro sdílení IPD
- PROTOKOL STUDY
- MÍZA
- ICF
Informace o lécích a zařízeních, studijní dokumenty
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