PNOC035: A platform study of novel therapies for children, adolescents and young adults with recurrent/progressive atypical teratoid rhabdoid tumor (ATRT)
Summary
This is a multi-treatment arm platform study conducted through the Pacific Pediatric Neuro-oncology Consortium (PNOC) to assess the safety and efficacy of novel therapies and combinatorial strategies for participants with recurrent or progressive atypical teratoid rhabdoid tumor (ATRT).
Treatment Arm A evaluates the combination of gemcitabine (an IV chemotherapy) and paxalisib (an oral targeted therapy).
In the Phase I portion, dose-limiting toxicities will be monitored to confirm the Recommended Phase 2 Dose (RP2D).
In Phase II, participants will receive the combination over 28-day cycles (gemcitabine on Days 1, 8, and 15; daily paxalisib) for up to 24 cycles to evaluate clinical benefit rate, progression-free survival, and overall response.
Trial Information
What is Gemcitabine and Paxalisib? Gemcitabine is a chemotherapy drug administered intravenously that works by inhibiting DNA synthesis in rapidly dividing cancer cells. Paxalisib is an oral, brain-penetrant small molecule inhibitor targeting the PI3K/Akt/mTOR pathway, which is frequently dysregulated in pediatric brain tumors. Used in combination, these therapies aim to simultaneously block critical survival pathways and induce cellular damage in recurrent or progressive ATRT cells to enhance antitumor activity.
Approach
Primary Objective:
Phase I: To evaluate the safety, tolerability, and recommended phase 2 dose (RP2D) of gemcitabine in combination with paxalisib in participants with recurrent or progressive ATRT.
Phase II: To assess the efficacy of each treatment arm based on arm-specific endpoints, including Clinical Benefit Rate (CBR, defined as complete response + partial response + stable disease sustained over 4 months).
Exploratory Objectives:
To collect additional treatment arm-specific safety and tolerability information. To determine additional time-to-event endpoints. To assess correlations between methylation-based subgroups and objective response/outcome measures. To collect biologic samples (tumor, blood, CSF) for future biomarker discovery.
Additional Information
NCT07447076
Full Details on ClinicalTrials.Gov
Eligibility
For this trial, patients must be ≥ 1 year and ≤ 39 years old with recurrent or progressive CNS ATRT.
For full Inclusion and exclusion criteria please visit: https://clinicaltrials.gov/study/NCT07447076
Contact Information
Principal Investigator: Sabine Mueller, MD, PhD
University of California, San Francisco (UCSF), San Francisco, California
Additional Contacts:
Email: PNOC035@ucsf.edu or info@pnoc.us
Phone: (415) 502-1600