LeiomyosarcomaPhase 1NCT06308419
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
A Phase 1 study testing Gemcitabine and Nab-Sirolimus in people with Leiomyosarcoma and Soft-tissue Sarcomas, run by M.D. Anderson Cancer Center at 1 site in United States.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Leiomyosarcoma, Soft-tissue Sarcomas
- What is being tested?
- Gemcitabine and Nab-Sirolimus
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 18 participants
- Where
- 1 siteUnited States
- Study dates
- 14 Aug 2024to 1 Feb 2031
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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%,).
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- Life expectancy of >3 months, as determined by the investigator.
- Patients must have adequate organ and marrow function as defined below:
- 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.
- The effects of nab-sirolimus on the developing human fetus are unknown. For this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) from the time of study entry and for the duration of study participation. (Refer to Pregnancy Assessment Policy MD Anderson Institutional Policy # CLN1114). Negative serum HCG will be required before study drug administration. This includes all female patients, between the onset of menses (as early as 8 years of age) and 55 years unless the patient presents with an applicable exclusionary factor which may be one of the following:
- 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).
- History of bilateral tubal ligation or another surgical sterilization procedure.
- Approved methods of birth control are as follows: Hormonal contraception (i.e. birth control pills, injection, implant, transdermal patch, vaginal ring), Intrauterine device (IUD), Tubal Ligation or hysterectomy, Patient/Partner post vasectomy, Implantable or injectable contraceptives, and condoms plus spermicide. Not engaging in sexual activity for the total duration of the trial and the drug washout period is an acceptable practice; however periodic abstinence, the rhythm method, and the withdrawal method are not acceptable methods of birth control. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately.
- Ability to understand and the willingness to sign a written informed consent document.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
1 site in 1 country.
About this study
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.
Read the 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
- Being tested
- Gemcitabine, Nab-Sirolimus
- Medical subject headings
- Leiomyosarcoma, Sarcoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GemcitabineDrug
Also called Gemcitabine Hydrochloride, Gemzar®
Given by IV
Nab-SirolimusDrug
Given by IV
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Gemcitabine; Drug: Nab-Sirolimus |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: Through study completion; an average of 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Mar 2024
- Study start14 Aug 2024
- Primary completion1 Feb 2029 (estimated)
- Study completion1 Feb 2031 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for LeiomyosarcomaStudies of the same condition, open and under way.
- More trials run by M.D. Anderson Cancer CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 18 participants (actual)
Sponsor and investigators
- Lead sponsor
- M.D. Anderson Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- Aadi Bioscience
- Responsible party
- Sponsor
- Investigators
- Neeta Somaiah, MD, Principal investigator, M.D. Anderson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06308419
- Sponsor's protocol ID
- 2023-0900
- Other IDs
- NCI-2024-01751
- Status last verified
- Oct 2026
- First submitted
- 23 Feb 2024
- Last updated
- 27 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 27 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT06308419
- Acronym / sponsor ID
- 2023-0900
- Conditions
- Leiomyosarcoma, Soft-tissue Sarcomas
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 18 participants (actual)
- Lead sponsor
- M.D. Anderson Cancer CenterUniversity, hospital or other
- Collaborators
- Aadi Bioscience
- Study start
- 14 Aug 2024 (actual)
- Primary completion
- 1 Feb 2029 (estimated)
- Study completion
- 1 Feb 2031 (estimated)
- First posted
- 13 Mar 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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,
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Gemcitabine + Nab-sirolimus | Experimental | Drug: Gemcitabine, Drug: Nab-SirolimusParticipants 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (19 listed)
- 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.
Key exclusion criteria (13 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| GemcitabineAlso: Gemcitabine Hydrochloride, Gemzar®Given by IV | Drug | Gemcitabine + Nab-sirolimus |
| Nab-SirolimusGiven by IV | Drug | Gemcitabine + Nab-sirolimus |
Primary outcome
Safety and adverse events (AEs)
Time frame: Through study completion; an average of 1 year
Incidence of Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Oct 2026.
- MD Anderson Cancer CenterLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Neeta Somaiah, MD principal investigator
M.D. Anderson Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Gemcitabine and Nab-Sirolimus in people with Leiomyosarcoma and Soft-tissue Sarcomas, run by M.D. Anderson Cancer Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 19 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 27 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety and adverse events (AEs) (time frame: Through study completion; an average of 1 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Oct 2026.