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

Leiomyosarcoma Clinical Trial

Official title: 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 Not yet recruiting

Clinical Trial 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.

Clinical Trial 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, ;

Related Conditions & MeSH terms

• Leiomyosarcoma
• Sarcoma
• Soft-tissue Sarcomas

• NCT number: NCT06308419
• Study type: Interventional
• Source: M.D. Anderson Cancer Center
• Contact: Elise Nassif, MD
• Phone: (281) 460-0607
• Email: efnassif@mdanderson.org
• Status: Not yet recruiting
• Phase: Phase 1
• Start date: July 31, 2024
• Completion date: February 1, 2031