NCT06308419

A Phase I Trial of Combination Gemcitabine and Nab-Sirolimus in Advanced Leiomyosarcomas or Advanced Soft-Tissue Sarcomas With TSC2 or TSC1 Loss-of-function Mutations or Deletions

• Status: Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 18 (estimated)
• Sponsor: M.D. Anderson Cancer Center · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

To find a recommended dose of gemcitabine and nab-sirolimus that can be given in combination to participants with advanced leiomyosarcomas or soft-tissue sarcomas.

Detailed description

Primary Objectives: * To estimate the Maximum Tolerated Dose (MTD) of gemcitabine and nab-sirolimus combination in patients with advanced leiomyosarcomas or advanced soft-tissue sarcomas with TSC2 or TSC1 loss-of-function mutations or deletions. Secondary Objectives * To estimate the rate of toxicity in the combination of gemcitabine and nab-sirolimus in participants with advanced leiomyosarcomas or advanced soft-tissue sarcomas with TSC2 or TSC1 loss-of-function mutations or deletions. * To describe anti-tumor activity (ORR) by radiographic evaluation (RECIST 1.1) * To describe Progression-Free Survival (PFS) and Overall Survival (OS). Exploratory Objectives * To estimate the rate of detection of ctDNA in blood samples of participants with advanced leiomyosarcomas or advanced soft-tissue sarcomas with TSC2 or TSC1 loss-of-function mutations or deletions. * To describe the relationship of ctDNA changes in blood samples and anti-tumor activity of gemcitabine and nab-sirolimus in patients with advanced leiomyosarcomas or advanced soft-tissue sarcomas with TSC2 or TSC1 loss-of-function mutations or deletions. * To describe the relationship between baseline expression of pERK1/2 by IHC on tumor samples and anti-tumor activity of gemcitabine and nab-sirolimus in participants with advanced leiomyosarcomas or advanced soft-tissue sarcomas with TSC2 or TSC1 loss-of-function mutations or deletions. * To describe the relationship between decreased expression of pAKT and pS6 after two cycles of gemcitabine and nab-sirolimus and anti-tumor activity in participants with advanced leiomyosarcomas or advanced soft-tissue sarcomas with TSC2 or TSC1 loss-of-function mutations or deletions. * To obtain discovery genomic data with RNA sequencing and whole genome sequencing for rare tumors (planned through the MD Anderson Cancer Center Patient Mosaic project). This will be part of a separate IRB-approved consent, which includes RNA sequencing and whole genome sequencing of the tumor and whole genome sequencing of the germline. The Patient Mosaic project takes a patient-centric approach to learn more about different cancer types, with a focus on rare cancers. This approach includes comprehensive molecular profiling including: germline whole genome sequencing, tumor whole genome sequencing, tumor transcriptome sequencing, and gut microbiome sequencing,

Conditions

• Leiomyosarcoma
• Soft-tissue Sarcomas

Interventions

Type	Name	Description
DRUG	Gemcitabine	Given by IV
DRUG	Nab-Sirolimus	Given by IV

Timeline

• Start date: 2024-08-14
• Primary completion: 2029-02-01
• Completion: 2031-02-01
• First posted: 2024-03-13
• Last updated: 2026-02-25

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study