Efficacy and Safety of Intrathecal Administration of Thiotepa in Combination With Methotrexate in Breast Cancer With Leptomeningeal Metastasis

August 6, 2024 updated by: The First Affiliated Hospital with Nanjing Medical University

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

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Estimated)

22

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • China
    • Jiangsu
      • Nanjing, Jiangsu, China, 210000
        • Recruiting
        • Jiangsu Provincial People's Hospital
        • Principal Investigator:
          • Wei Li, Ph.D
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Patient is an adult female ≥18 and ≤75 years old at the time of informed consent.
  2. ECGO rating 0-3.
  3. Histologically or cytologically confirmed breast cancer.
  4. Cerebrospinal fluid cytology combined with central nervous system function and brain imaging demonstrated the diagnosis of breast cancer with meningeal metastases;
  5. Patients can be implanted or have been implanted with Ommaya reservoirs;
  6. Patient must have at least one measurable lesion (according to RECIST 1.1 criteria);
  7. 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.

  8. 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.

Exclusion Criteria:

  1. Patients with other malignant tumors, excluding basal cell carcinoma and carcinoma in situ
  2. Patients with severe or uncontrolled systemic disease, including uncontrolled hypertension or active bleeding tendency
  3. The investigator considers the patient unsuitable for entry into this study.
  4. Patients with toxicity from prior therapy that has not returned to normal or NCI-CTCAE grade 5.0
  5. Patients who have a drug allergy or metabolic disorder to the drugs in this regimen
  6. 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).
  7. Patients who are concurrently enrolled in other clinical studies

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Intrathecal chemotherapy group
Patients received intrathecal 15mg MTX combination with 10mg thiotepa twice a week for 2 weeks (4 injections) followed by monthly injections of 15mg MTX combination with 10mg thiotepa until an event that meets the criteria for termination occurs.
Drug: Intrathecal Administration of Thiotepa in Combination with Methotrexate via the Ommaya Reservoir
Patients received intrathecal 15mg MTX combination with 10mg thiotepa twice a week for 2 weeks (4 injections) followed by monthly injections of 15mg MTX combination with 10mg thiotepa until an event that meets the criteria for termination occurs.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
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 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.
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
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.
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
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.
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
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.
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
Overall survival is defined as the time from the date of randomization to the date of death due to any cause
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
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.
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
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

The First Affiliated Hospital with Nanjing Medical University

Collaborators

The Affiliated Brain Hospital of Nanjing Medical University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 13, 2024

Primary Completion (Estimated)

December 13, 2026

Study Completion (Estimated)

December 13, 2026

Study Registration Dates

First Submitted

July 26, 2024

First Submitted That Met QC Criteria

August 6, 2024

First Posted (Actual)

August 9, 2024

Study Record Updates

Last Update Posted (Actual)

August 9, 2024

Last Update Submitted That Met QC Criteria

August 6, 2024

Last Verified

August 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Ommaya 01

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • ICF
  • ANALYTIC_CODE
  • CSR

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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