Leptomeningeal Metastasis of Breast CancerPhase 2NCT06543992
Efficacy and Safety of Intrathecal Administration of Thiotepa in Combination With Methotrexate in Breast Cancer With Leptomeningeal Metastasis
A Phase 2 study testing Intrathecal Administration of Thiotepa in Combination with Methotrexate via the Ommaya Reservoir in people with Leptomeningeal Metastasis of Breast Cancer, run by The First Affiliated Hospital with Nanjing Medical University at 1 site in China.
Trial summary
Evaluate the efficacy and safety of Intrathecal Administration of Thiotepa in Combination with Methotrexate via the Ommaya Reservoir in Breast Cancer with Leptomeningeal Metastasis Read more about this study
- Who is it for?
- Ages 18 to 75 years, women only
- Conditions the study is for
- Leptomeningeal Metastasis of Breast Cancer
- What is being tested?
- Intrathecal Administration of Thiotepa in Combination with Methotrexate via the Ommaya Reservoir
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 22 participants
- Where
- 1 siteChina
- Study dates
- 8 Aug 2024to 13 Dec 2026
- Phase
- Phase 2
- 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 to 75 years
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patient is an adult female ≥18 and ≤75 years old at the time of informed consent.
- ECGO rating 0-3.
- Histologically or cytologically confirmed breast cancer.
- A new diagnosis of LM, established either by the presence of malignant cells in the CSF or by the combination of characteristic clinical manifestations and magnetic resonance imaging (MRI) findings
- Patients can be implanted or have been implanted with Ommaya reservoirs;
- Patient must have at least one measurable lesion (according to RECIST 1.1 criteria);
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- Postmenopausal or pre/perimenopausal female patients are eligible for enrolment; pre or perimenopausal female patients must be willing to receive LHRHa during the study period.
- All patients were required to meet the following laboratory biochemical values prior to enrolment:
- Haematology: Hb ≥90 g/L, WBC ≥3.5×109/L, ANC ≥1.5×109/L, PLT ≥100×109/L;
- Liver function: for those without liver metastases, AST, ALT, ALP ≤2.5 times the upper limit of normal values, and ≤1.25 x the upper limit of normal values for total bilirubin; for those with liver metastases, AST, ALT, ALP ≤ 5 times the upper limit of normal value, and total bilirubin ≤ 1.5 x upper limit of normal value.
Who cannot join
- Patients with other malignant tumors, excluding basal cell carcinoma and carcinoma in situ
- Patients with severe or uncontrolled systemic disease, including uncontrolled hypertension or active bleeding tendency
- The investigator considers the patient unsuitable for entry into this study.
- Patients with toxicity from prior therapy that has not returned to normal or NCI-CTCAE grade 5.0
- Patients who have a drug allergy or metabolic disorder to the drugs in this regimen
- Pregnant or lactating women (women of childbearing age must have had a negative pregnancy test within 14 days prior to the first dose; if positive, pregnancy must be ruled out by ultrasound).
- Patients who are concurrently enrolled in other clinical studies
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site, 1 recruiting
- Recruiting
Jiangsu Provincial People's Hospital
Nanjing, Jiangsu, 210000
Wei Li, Ph.D, 25-68307102, real.lw@163.com
Wei Li, Ph.D
About this study
Official title: Efficacy and Safety of Intrathecal Administration of Thiotepa in Combination With Methotrexate Via the Ommaya Reservoir in Breast Cancer With Leptomeningeal Metastasis: a Phase II Multicenter Clinical Trial
Evaluate the efficacy and safety of Intrathecal Administration of Thiotepa in Combination with Methotrexate via the Ommaya Reservoir in Breast Cancer with Leptomeningeal Metastasis
Read the detailed description
This was a II, single-arm, prospective, multicenter study designed to estimate the efficacy and safety of intrathecal administration of thiotepa in combination with methotrexate via the Ommaya Reservoir in breast cancer with leptomeningeal metastasis.
The primary end point was iORR [complete response (CR) + partial response (PR)] according to RANO-LM. Scoring based on radiographic assessment in leptomeningeal metastases . A composite score (total score) is calculated and compared with the baseline total score. A 25% worsening in the current score relative to baseline defines radiographic progressive disease. A 50% improvement in the current score defines a radiographic partial response. Resolution of all baseline radiographic abnormalities defines a complete response. All other situations define stable disease. The secondary end points were changes in iPFS, iDoR, ORR, PFS, OS, DoR and exploratory analysis of the relationship between molecular markers and therapeutic efficacy.
This study is planned to include 22 patients with leptomeningeal metastasis from breast cancer who meet the entry criteria.
- Being tested
- Intrathecal Administration of Thiotepa in Combination with Methotrexate via the Ommaya Reservoir
- Keywords
- methotrexate, thiotepa, intrathecal chemotherapy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Intrathecal Administration of Thiotepa in Combination with Methotrexate via the Ommaya ReservoirDrug
Patients received 15 mg MTX intrathecally combined with 10 mg thiotepa twice a week for 2 weeks (4 injections), followed by a maintenance phase in which the same agents and dosages were administered every three weeks until an event meeting the termination criteria occurs.
| Study group | Role | What they receive |
|---|---|---|
| Intrathecal chemotherapy group | Experimental | Intraventricular administration was carried out using an Ommaya reservoir. The treatment protocol consisted of an induction phase: thiotepa (10 mg) and MTX (15 mg) were administered twice weekly for a total of four consecutive doses, followed by a maintenance phase in which the same agents and dosages were administered every three weeks. Treatment was continued until the occurrence of an event meeting predefined discontinuation criteria. Receives: Drug: Intrathecal Administration of Thiotepa in Combination with Methotrexate via the Ommaya Reservoir |
What is being measured
The primary outcome is the main question the study is designed to answer.
Intracranial Overall Response Rate
Intracranial overall response rate (iORR) is defined as the proportion of patients whose best overall response is either complete response (CR) or partial response (PR), as per local review and according to RANO-LM.
Measured: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months
Secondary outcomes (7)
Intracranial Progression Free Survival
Intracranial progression-free survival (iPFS) is defined as the time from the date of randomization to the date of the first documented progression, as per local review and according to RANO-LM or death due to any cause.
Measured: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months
Intracranial Duration of Response
Intracranial duration of response (iDoR) is defined as the time from randomization to disease progression or death in patients who achieve complete or partial response, as per local review and according to RANO-LM.
Measured: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months
Overall Response Rate
Overall response rate (ORR) is defined as the proportion of patients whose best overall response is either complete response (CR) or partial response (PR), as per local review and according to RECIST 1.1.
Measured: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months
Progression Free Survival
Progression-free survival (PFS) is defined as the time from the date of randomization to the date of the first documented progression as per local review and according to RECIST 1.1 or death due to any cause.
Measured: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months
Overall Survival
Overall survival is defined as the time from the date of randomization to the date of death due to any cause
Measured: From date of randomization until the date of death from any cause, assessed up to 100 months
Duration of Response
Duration of response (DoR) is defined as the time from randomization to disease progression or death in patients who achieve complete or partial response, as per local review and according to RECIST 1.1.
Measured: From date of randomization until the date of death from any cause, assessed up to 100 months
frequency/severity of adverse events, lab abnormalities
Number of participants with treatment-related adverse events as assessed by CTCAE v5.0
Measured: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Aug 2024
- Study start8 Aug 2024
- Primary completion13 Dec 2026 (estimated)
- Study completion13 Dec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Leptomeningeal Metastasis of Breast CancerStudies of the same condition, open and under way.
- More trials run by The First Affiliated Hospital with Nanjing Medical UniversityThe 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 22 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Collaborators
- The Affiliated Brain Hospital of Nanjing Medical University
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06543992
- Sponsor's protocol ID
- NJMU-BC04
- Status last verified
- Jul 2025
- First submitted
- 26 Jul 2024
- Last updated
- 21 Jul 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 21 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy and Safety of Intrathecal Administration of Thiotepa in Combination With Methotrexate Via the Ommaya Reservoir in Breast Cancer With Leptomeningeal Metastasis: a Phase II Multicenter Clinical Trial
- ClinicalTrials.gov ID
- NCT06543992
- Acronym / sponsor ID
- NJMU-BC04
- Keywords
- methotrexate, thiotepa, intrathecal chemotherapy
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 22 participants (estimated)
- Lead sponsor
- The First Affiliated Hospital with Nanjing Medical UniversityUniversity, hospital or other
- Collaborators
- The Affiliated Brain Hospital of Nanjing Medical University
- Study start
- 8 Aug 2024 (actual)
- Primary completion
- 13 Dec 2026 (estimated)
- Study completion
- 13 Dec 2026 (estimated)
- First posted
- 9 Aug 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.
Evaluate the efficacy and safety of Intrathecal Administration of Thiotepa in Combination with Methotrexate via the Ommaya Reservoir in Breast Cancer with Leptomeningeal Metastasis
Detailed description
This was a II, single-arm, prospective, multicenter study designed to estimate the efficacy and safety of intrathecal administration of thiotepa in combination with methotrexate via the Ommaya Reservoir in breast cancer with leptomeningeal metastasis.
The primary end point was iORR [complete response (CR) + partial response (PR)] according to RANO-LM. Scoring based on radiographic assessment in leptomeningeal metastases . A composite score (total score) is calculated and compared with the baseline total score. A 25% worsening in the current score relative to baseline defines radiographic progressive disease. A 50% improvement in the current score defines a radiographic partial response. Resolution of all baseline radiographic abnormalities defines a complete response. All other situations define stable disease. The secondary end points were changes in iPFS, iDoR, ORR, PFS, OS, DoR and exploratory analysis of the relationship between molecular markers and therapeutic efficacy.
This study is planned to include 22 patients with leptomeningeal metastasis from breast cancer who meet the entry criteria.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Intrathecal chemotherapy group | Experimental | Drug: Intrathecal Administration of Thiotepa in Combination with Methotrexate via the Ommaya ReservoirIntraventricular administration was carried out using an Ommaya reservoir. The treatment protocol consisted of an induction phase: thiotepa (10 mg) and MTX (15 mg) were administered twice weekly for a total of four consecutive doses, followed by a maintenance phase in which the same agents and dosages were administered every three weeks. Treatment was continued until the occurrence of an event meeting predefined discontinuation criteria. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Patient is an adult female ≥18 and ≤75 years old at the time of informed consent.
- ECGO rating 0-3.
- Histologically or cytologically confirmed breast cancer.
- A new diagnosis of LM, established either by the presence of malignant cells in the CSF or by the combination of characteristic clinical manifestations and magnetic resonance imaging (MRI) findings
- Patients can be implanted or have been implanted with Ommaya reservoirs;
Key exclusion criteria (7 listed)
- Patients with other malignant tumors, excluding basal cell carcinoma and carcinoma in situ
- Patients with severe or uncontrolled systemic disease, including uncontrolled hypertension or active bleeding tendency
- The investigator considers the patient unsuitable for entry into this study.
- Patients with toxicity from prior therapy that has not returned to normal or NCI-CTCAE grade 5.0
- Patients who have a drug allergy or metabolic disorder to the drugs in this regimen
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 |
|---|---|---|
| Intrathecal Administration of Thiotepa in Combination with Methotrexate via the Ommaya ReservoirPatients received 15 mg MTX intrathecally combined with 10 mg thiotepa twice a week for 2 weeks (4 injections), followed by a maintenance phase in which the same agents and dosages were administered every three weeks until an event meeting the termination criteria occurs. | Drug | Intrathecal chemotherapy group |
Primary outcome
Intracranial Overall Response Rate
Time frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months
Intracranial overall response rate (iORR) is defined as the proportion of patients whose best overall response is either complete response (CR) or partial response (PR), as per local review and according to RANO-LM.
7 secondary outcomes
Intracranial Progression Free Survival
Time frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months
Intracranial Duration of Response
Time frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months
Overall Response Rate
Time frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months
Progression Free Survival
Time frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months
Overall Survival
Time frame: From date of randomization until the date of death from any cause, assessed up to 100 months
Duration of Response
Time frame: From date of randomization until the date of death from any cause, assessed up to 100 months
frequency/severity of adverse events, lab abnormalities
Time frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months
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 21 Jul 2026.
- Individual participant dataSharing planned: Yes
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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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Intrathecal Administration of Thiotepa in Combination with Methotrexate via the Ommaya Reservoir in people with Leptomeningeal Metastasis of Breast Cancer, run by The First Affiliated Hospital with Nanjing Medical University at 1 site in China.
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 10 inclusion and 7 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: looking for participants now, as of the sponsor's last update on 21 Jul 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 China. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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?
Contact Wei Li, Ph.D (025-68307102, real.lw@163.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Intracranial Overall Response Rate (time frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months). 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 21 Jul 2026.