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.
Study Overview
Status
Conditions
Detailed Description
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.
Study Type
Enrollment (Estimated)
Phase
- Phase 2
Contacts and Locations
Study Contact
- Name: Tabatha E. Doyle, RN
- Phone Number: 901-595-2544
- Email: tabatha.doyle@stjude.org
Study Locations
-
-
Tennessee
-
Memphis, Tennessee, United States, 38105
- St. Jude Children's Research Hospital
-
Contact:
- Tabatha E. Doyle, RN
- Phone Number: 901-595-2544
- Email: tabatha.doyle@stjude.org
-
Principal Investigator:
- Aditi Bagchi, M.D., Ph.D.
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
|---|---|
|
Experimental: Stratum A
|
By mouth, nasogastric, or gastronomy/stomach tube, Day 1-28
Other Names:
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.
Other Names:
IV (intravenous) day 1
Other Names:
IV (intravenous) days 1 and 2
Other Names:
IV (intravenous) day 2
Other Names:
Subcutaneous (under the skin) or IV (intravenous) day 3
Other Names:
Subcutaneous (under the skin) day 3
Other Names:
|
|
Experimental: 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.
Other Names:
IV (intravenous) day 1
Other Names:
IV (intravenous) days 1 and 2
Other Names:
IV (intravenous) day 2
Other Names:
Subcutaneous (under the skin) or IV (intravenous) day 3
Other Names:
Subcutaneous (under the skin) day 3
Other Names:
By mouth, nasogastric, or gastronomy/stomach tube, Day 1-28
Other Names:
|
|
Experimental: 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.
Other Names:
IV (intravenous) day 1
Other Names:
IV (intravenous) days 1 and 2
Other Names:
IV (intravenous) day 2
Other Names:
Subcutaneous (under the skin) day 3
Other Names:
|
|
Experimental: Stratum D
Participants who have no measurable residual disease at the time of enrollment.
|
IV (intravenous) day 1
Other Names:
IV (intravenous) days 1 and 2
Other Names:
IV (intravenous) day 2
Other Names:
Subcutaneous (under the skin) or IV (intravenous) day 3
Other Names:
Subcutaneous (under the skin) day 3
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Rate of Complete Tumor Response (CTR) among patients in Strata A, B, and C
Time Frame: 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
Time Frame: 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
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Event free survival (EFS)
Time Frame: 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)
Time Frame: 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
Time Frame: 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
Time Frame: 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
|
Collaborators and Investigators
Investigators
- Principal Investigator: Aditi Bagchi, M.D., Ph.D., St. Jude Children's Research Hospital
Publications and helpful links
Study record dates
Study Major Dates
Study Start (Estimated)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
- Surgery
- Brain Tumor
- Newly Diagnosed
- Adjuvant treatment
- Neoadjuvant treatment
- 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
Additional Relevant MeSH Terms
- Brain Diseases
- Central Nervous System Diseases
- Nervous System Diseases
- Neoplasms by Site
- Neoplasms
- Nervous System Neoplasms
- Central Nervous System Neoplasms
- Brain Neoplasms
- Peptides
- Amino Acids, Peptides, and Proteins
- Proteins
- Organic Chemicals
- Hydrocarbons
- Hydrocarbons, Cyclic
- Biological Factors
- Carbohydrates
- Podophyllotoxin
- Tetrahydronaphthalenes
- Naphthalenes
- Polycyclic Aromatic Hydrocarbons
- Hydrocarbons, Aromatic
- Polycyclic Compounds
- Glucosides
- Glycosides
- Coordination Complexes
- Phosphoramide Mustards
- Nitrogen Mustard Compounds
- Mustard Compounds
- Hydrocarbons, Halogenated
- Phosphoramides
- Organophosphorus Compounds
- Intercellular Signaling Peptides and Proteins
- Glycoproteins
- Glycoconjugates
- Colony-Stimulating Factors
- Hematopoietic Cell Growth Factors
- Cytokines
- Cyclophosphamide
- Etoposide
- Carboplatin
- Surgical Procedures, Operative
- Granulocyte Colony-Stimulating Factor
- Filgrastim
- entrectinib
- pegfilgrastim
- alectinib
Other Study ID Numbers
- SJIHG25
- NCI-2026-07231 (Registry Identifier: NCI Clinical Trial Registration Program)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
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 Sharing Time Frame
Data will be made available at the time of article publication.
IPD Sharing Access Criteria
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 Sharing Supporting Information Type
- STUDY_PROTOCOL
- SAP
- ICF
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
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