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

NCT06308419 | Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: 2023-0900NCI-2024-01751
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Leiomyosarcoma; Soft-tissue Sarcomas

Outcome Measures

Primary Outcomes (1)

• Safety and adverse events (AEs)

  Incidence of Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0

  Through study completion; an average of 1 year

Study Arms (1)

Gemcitabine + Nab-sirolimus

EXPERIMENTAL

Participants found to be eligible to take part in this study, participants will be assigned to a dose level of gemcitabine and nab-sirolimus based on when participants join this study.

Drug: Gemcitabine; Drug: Nab-Sirolimus

Interventions

Gemcitabine DRUG

Given by IV

Also known as: Gemcitabine Hydrochloride, Gemzar®

Gemcitabine + Nab-sirolimus

Nab-Sirolimus DRUG

Given by IV

Gemcitabine + Nab-sirolimus

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have histologically confirmed leiomyosarcoma or sarcoma with TSC2 or TSC1 loss-of-function mutations or deletions based on standard-of-care genomic testing.
• Sarcoma that is metastatic or unresectable and for which standard curative measures do not exist or are no longer effective. One prior standard systemic therapy is required for leiomyosarcoma (LMS) Patients.
• Prior gemcitabine-based chemotherapy is allowed if the last dose of gemcitabine was given more than 12 months prior to the first dose of treatment on trial, there was no progression of disease while on treatment with gemcitabine, and there was intolerable toxicity.
• Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as ≥20 mm (≥2 cm) by chest x-ray or as ≥10 mm (≥1 cm) with CT scan, MRI, or calipers by clinical exam.
• Age ≥18 years. Because no dosing or adverse event data are currently available on the use of nab-sirolimus in combination with gemcitabine in patients \<18 years of age, children are excluded from this study.
• ECOG performance status ≤2 (Karnofsky ≥60%,).
• Life expectancy of \>3 months, as determined by the investigator.
• Patients must have adequate organ and marrow function as defined below:
• i. absolute neutrophil count ≥1,500/mcL ii. platelets ≥100,000/mcL iii. hemoglobin ≥9 gm/dL iv. total bilirubin ≤ 2 x institutional upper limit of normal (ULN) (except patients with Gilbert's syndrome, who must have total bilirubin \< 3.0 mg/dL) v. AST(SGOT)/ALT(SGPT) ≤2 × institutional ULN vi. eGFR (calculated by CKD-EPI) ≥ 60 mL/min vii. Serum triglyceride \<300 mg/dL viii. Serum cholesterol \<350 mg/dL
• For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated.
• Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For Participants with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load.
• Patients with Human Immunodeficiency Virus (HIV) with a viral load \<400copies/mL, no IADS-defining illness within 12 months of enrollment, and no CYP3A4 inducers or inhibitors in the antiretroviral treatment.
• Patients with treated brain metastases are eligible if follow-up brain imaging after central nervous system (CNS)-directed therapy shows no evidence of progression.
• Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class 2B or better.
• Postmenopausal (no menses in greater than or equal to 12 consecutive months). History of hysterectomy or bilateral salpingo-oophorectomy. Ovarian failure (Follicle Stimulating Hormone and Estradiol in menopausal range).

You may not qualify if:

• Patients who are receiving any other investigational agents or have received any other investigational agent within 3 weeks prior to enrollment.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to nab-sirolimus or gemcitabine.
• Use of strong inhibitors and inducers of CYP3A4 within the 7 days prior to receiving the first dose of nab-sirolimus. Additionally, use of any known CYP3A4 substrates with narrow therapeutic window (such as fentanyl, alfentanil, astemizole,cisapride, dihydroergotamine, pimozide, quinidine, terfanide) within the 7 days prior to receiving the first dose of nab-sirolimus.
• Patients with active concurrent malignancy.
• Recent stroke or thromboembolic event (within 6 months) requiring anticoagulation that cannot be interrupted. Non-life threatening deep venous thrombosis on stable anticoagulation within 6 months is allowed.
• Active gastro-intestinal bleeding.
• Pre-existing thyroid abnormality is allowed provided thyroid can be controlled with medication.
• Prior treatment with radiotherapy (including radio-labeled spheres and/or cyberknife, hepatic arterial embolization (with or without chemotherapy) or cyrotherapy/ablation) is allowed if these therapies did not affect the areas of measurable disease being used for this protocol.
• Uncontrolled diabetes mellitus as defined by HbA1c \>8% despite adequate therapy.
• Evidence of severe or uncontrolled systemic disease or any other concurrent condition, including psychiatric, that would significantly limit the ability to participate safely in this study.
• Pregnant women are excluded from this study because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with nab-sirolimus, breastfeeding should be discontinued if the mother is treated with nab-sirolimus. These potential risks may also apply to other agents used in this study.
• Prior treatment of sarcoma with mTOR inhibitors.
• Vulnerable populations will not be enrolled.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• Aadi Bioscience: collaborator

Study Sites (1)

MD Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

Related Links

• MD Anderson Cancer Center

MeSH Terms

Conditions

Leiomyosarcoma; Sarcoma

Interventions

Gemcitabine

Condition Hierarchy (Ancestors)

Neoplasms, Muscle Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring

Study Officials

• Elise Nassif, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Elise Nassif, MD

CONTACT

(281) 460-0607; efnassif@mdanderson.org

Gracy Zacharian, BSN,MSN,RN

CONTACT

(713) 792-2669; gzachari@mdanderson.org

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 23, 2024
• First Posted: March 13, 2024
• Study Start: August 14, 2024
• Primary Completion (Estimated): February 1, 2029
• Study Completion (Estimated): February 1, 2031
• Last Updated: February 25, 2026

Record last verified: 2026-02

Locations

US (1)