Study of Novel Therapies for Young People With Recurrent/Progressive Atypical Teratoid Rhabdoid Tumor (ATRT)

NCT07447076 | Not Yet Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 25083
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 1

Brief Summary

This is a multi-treatment arm study that will be conducted through the Pacific Pediatric Neuro-oncology Consortium (PNOC).The study will assess the safety and efficacy of novel therapies and combinatorial strategies for participants with recurrent or progressive ATRT.

Conditions

Recurrent Atypical Teratoid/Rhabdoid Tumor; Atypical Teratoid/Rhabdoid Tumor (ATRT) of the CNS

Keywords

Novel therapies

Outcome Measures

Primary Outcomes (3)

• Arm A (Phase I): Proportion of participants who experience dose-limiting toxicity (DLT)

  Tolerability is defined as the proportion of participants receiving at least one dose of combination gemcitabine and paxalisib with a reported dose-limiting toxicity (DLT) during cycle 1 for all participants in Phase I.

  up to 28 days

• Arm A (Phase I): Recommended Phase 2 Dose (RP2D) (Phase I)

  The confirmed RP2D of combination gemcitabine and paxalisib implemented for participants enrolled in Phase II will be reported.

  up to 28 days

• Arm A (Phase II): Rate of Clinical Benefit

  Assess the efficacy of combination gemcitabine and paxalisib for participants in Phase II. Clinical Benefit rate (CBR) is defined as complete response (CR) + partial response (PR) + stable disease (SD), where SD is sustained over 4 months.

  up to 2 years (24 cycles)

Study Arms (2)

Treatment Arm A: Phase I

EXPERIMENTAL

Participants will receive a combination of gemcitabine and paxalisib with starting dose, 1,200mg/m2 gemcitabine and 15mg/m2 paxalisib (phase I). If this dose level is tolerated, it will be confirmed as the RP2D. However, if the dose limiting toxicity (DLT) is not tolerated, the RP2D will be set at the highest dose level tolerated by the previous group.

Procedure: Lumber Puncture; Procedure: Blood Specimen Collection; Procedure: Magnetic resonance imaging (MRI); Drug: Gemcitabine; Drug: Paxalisib; Procedure: Tumor Biopsy

Treatment Arm A: Efficacy (Phase II)

EXPERIMENTAL

All participants will receive a combination of gemcitabine and paxalisib over a 28-day cycle, for up to 24 cycles or until they meet criteria to stop treatment, whichever comes first. Gemcitabine will be administered via infusion on days 1, 8, and 15 of each cycle, while paxalisib will be taken daily throughout each cycle.

Procedure: Lumber Puncture; Procedure: Blood Specimen Collection; Procedure: Magnetic resonance imaging (MRI); Drug: Gemcitabine; Drug: Paxalisib; Procedure: Tumor Biopsy

Interventions

Lumber Puncture PROCEDURE

Cerebral Spinal Fluid (CSF) will be collected for research

Treatment Arm A: Efficacy (Phase II); Treatment Arm A: Phase I

Blood Specimen Collection PROCEDURE

Perform blood draw

Treatment Arm A: Efficacy (Phase II); Treatment Arm A: Phase I

Magnetic resonance imaging (MRI) PROCEDURE

Undergo imaging procedure

Treatment Arm A: Efficacy (Phase II); Treatment Arm A: Phase I

Gemcitabine DRUG

Given IV

Treatment Arm A: Efficacy (Phase II); Treatment Arm A: Phase I

Paxalisib DRUG

Given orally (PO)

Treatment Arm A: Efficacy (Phase II); Treatment Arm A: Phase I

Tumor Biopsy PROCEDURE

Undergo biopsy

Treatment Arm A: Efficacy (Phase II); Treatment Arm A: Phase I

Eligibility Criteria

• Age: 1 Year - 39 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Participants must have a pathologic diagnosis of central nervous system (CNS) ATRT, with confirmation of SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin, subfamily b, member 1 (SMARCB1) (INI1) loss by immunohistochemistry (IHC) and/or biallelic loss of function of SMARCB1 by molecular report. Loss of SWI/SNF Related, Matrix Associated, Actin Dependent Regulator of Chromatin, Subfamily A, Member 4 (SMARCA4) as confirmed by IHC or molecular report is also acceptable but requires study chair approval.
• Participants must have confirmation of methylation report, co-enrollment on PNOC-030 or sufficient tumor tissue available for methylation-based subgrouping
• Participants must have recurrent or progressive ATRT.
• Prior Therapy: Participants must have fully recovered from the acute effects of prior anti-cancer therapy, and the following wash-out periods need to be observed prior to enrollment:
• Systemic myelosuppressive therapy: ≥ 21 days after the last dose (42 days for nitrosoureas or mitomycin C).
• Intrathecal/intraventricular chemotherapy: \> 7 days after the last dose.
• Small molecule/targeted/biologic agent: ≥ 7 days after the last dose.
• Monoclonal antibodies: ≥ 21 days after the last dose. Other non-myelosuppressive anti-cancer agents: ≥ 3 drug half-lives after the last dose.
• CAR-T cell therapy (systemic or intraventricular): \> 21 days.
• Previous radiotherapy. Participants will be eligible following radiotherapy, if they meet the following criteria:
• Previous craniospinal or total body radiotherapy: Participants must have received their last fraction ≥ 12 weeks prior to enrollment and have evidence of progressive/recurrent evaluable disease post radiation.
• Previous focal radiotherapy to target lesions: Participants must have received their last fraction to target lesions ≥12 weeks prior to enrollment and have evidence of progressive/recurrent evaluable disease post radiation; investigators are reminded to review potentially eligible cases to avoid confusion with pseudo-progression.
• Focal radiotherapy to non-target lesions: Participants may have received radiotherapy to nontarget lesions as long as the last fraction was \> 14 days prior to enrollment. Participants must have at least one non-irradiated lesion that is evaluable for response.
• Performance Score: Karnofsky ≥ 50 for participants \> 16 years of age and Lansky ≥ 50 for participants ≤ 16 years of age. Participants who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score.
• Organ Function Requirements.

You may not qualify if:

• Evidence of synchronous tumors or other extra-CNS malignancy
• Participants who are receiving any other investigational agents
• Participants who are currently receiving other anti-cancer agents
• Participants with uncontrolled infection or other uncontrolled systemic illness
• Female participants of childbearing potential who are pregnant or breast-feeding. Female participants of childbearing potential must have a negative serum or urine pregnancy test prior to the start of therapy and throughout study treatment.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition as the intended treatment regimen, as detailed in that arm's treatment description.
• Arm A
• Patients must be evaluable per Response Assessment in Pediatric Neuro-Oncology (RAPNO) criteria for medulloblastoma and other leptomeningeal seeding tumors to be evaluated for the primary endpoint (Warren et al. 2018); patients with evaluable but non-measurable disease, including leptomeningeal disease or positive CSF cytology only are eligible.
• Patients with recurrent or progressive ATRT who receive surgery only for their disease progression and do not have evaluable disease may be eligible for study treatment but would not be included towards the primary efficacy endpoint (to be discussed with study chairs).
• Subjects must be able to swallow intact capsules.
• Adequate Metabolic Function Defined as:
• Non-fasting glucose ≤ 140 milligrams per deciliter (mg/dL) without the use of antihyperglycemic agents.
• If non-fasting glucose \> 140 mg/dL, a fasting glucose should be done. If fasting glucose ≤ 125 mg/dL without the use of antihyperglycemic agents, participant will meet adequate metabolic function criteria.
• Triglycerides of \< 300 mg/dl and total cholesterol of \< 300 mg/dl - can be on lipid lowering medications as needed to achieve.
• Adequate Cardiac Function Defined as:

Sponsors & Collaborators

• Sabine Mueller, MD, PhD: lead
• Pacific Pediatric Neuro-Oncology Consortium: collaborator
• Rally Foundation: collaborator

Study Sites (1)

University of California, San Francisco

San Francisco, California, 94143, United States

Location

MeSH Terms

Conditions

Rhabdoid Tumor

Interventions

Blood Specimen Collection; Magnetic Resonance Spectroscopy; Gemcitabine

Condition Hierarchy (Ancestors)

Neoplasms, Complex and Mixed; Neoplasms by Histologic Type; Neoplasms

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques; Spectrum Analysis; Chemistry Techniques, Analytical; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring

Study Officials

• Sabine Mueller, MD, PhD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

• Ashley Margol, MD, MS

  Children's Hospital Los Angeles

  STUDY CHAIR

Central Study Contacts

PNOC Operations Office

CONTACT

415-502-1600; PNOC035@ucsf.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: February 25, 2026
• First Posted: March 3, 2026
• Study Start: May 1, 2026
• Primary Completion (Estimated): December 31, 2035
• Study Completion (Estimated): December 31, 2036
• Last Updated: March 3, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)