Concurrent Intrathecal-pemetrexed and Involved-field Radiotherapy for Leptomeningeal Metastasis From Solid Tumors

December 23, 2019 updated by: Zhenyu Pan, The First Hospital of Jilin University

Intrathecal-pemetrexed Combined With Concurrent Involved-field Radiotherapy for Leptomeningeal Metastasis From Solid Tumor: a Phase I/II Clinical Trial

Intrathecal chemotherapy is one of the most important treatment modalities for leptomeningeal metastasis of solid tumors. In the previous retrospective study, it has been proved that concurrent radiotherapy and intrathecal methotrexate for leptomeningeal metastasis from solid tumors with adverse prognostic factors showed great effectiveness and safety. The preliminary results of investigators' current prospective clinical study (Involved-field Radiotherapy Combined With Concurrent Intrathecal-methotrexate Versus Intrathecal-Ara-C for Leptomeningeal Metastases From Solid Tumor: A Randomized Phase II Clinical Trial. ClinicalTrials.gov identification number: NCT03082144) also showed that the regimen of concurrent intrathecal chemotherapy and radiotherapy may serve as an optimal therapeutic option for treatment of leptomeningeal metastases from solid tumors. Pemetrexed is a newer multitargeted antifolate which has shown activity in various tumors. In investigators' current study (Intrathecal Pemetrexed for Recurrent Leptomeningeal Metastasis From Non-small Cell Lung Cancer: A Prospective Pilot Clinical Trial. ClinicalTrials.gov identification number: NCT03101579), the regimen of intrathecal pemetrexed with folic acid and vitamin B12 supplementation may provide higher effectiveness and safety for recurrent leptomeningeal metastasis from non-small cell lung cancer. Therefore, the purpose of the study is to evaluate the tolerability, safety and effectiveness of intrathecal pemetrexed combined with involved-field radiotherapy as the first line treatment in patients with leptomeningeal metastases from malignant solid tumors.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

This study is a single arm, open clinical trial. Consecutive patients with leptomeningeal metastases from malignant solid tumors are enrolled into this study. Concomitant regimen consisted of intrathecal chemotherapy (via lumbar puncture, pemetrexed 10 mg, plus dexamethasone 5 mg, once per week, 5 to 8 times, 4 to 7 weeks in total) and radiotherapy. Radiotherapy consisted of fractionated, conformal radiation given at a daily dose of 2 Gy. The planning volume consisted of sites of symptomatic disease, bulky disease observed on magnetic resonance imaging(MRI), including the whole brain and basis cranii received 40 Gy in 20 fractions, 4 weeks in total, and/or segment of spinal canal received 40-50 Gy. The RANO proposal for response criteria of leptomeningeal metastasis was used to assess the clinical response in this study.

Study Type

Interventional

Enrollment (Actual)

34

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

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

Study Locations

  • China
    • Jilin
      • Changchun, Jilin, China, 130021
        • The First Hospital of Jilin University

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

16 years to 73 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Patients who have been definitely diagnosed as leptomeningeal metastasis according to cerebrospinal fluid (CSF) cytology, or patients who got the clinical diagnosis by combining history of cancer, neuroimaging, clinical manifestation, and CSF examination, etc.
  2. Patients who have been diagnosed as malignant solid tumor with definite pathologic type, excluding hematological malignancies (e.g., leukemia and lymphoma) or intracranial germ cell tumors;
  3. No severe abnormal liver function; normal kidney function; WBC≥4000/mm3, Plt≥110000/mm3;
  4. No other severe chronic diseases;
  5. No severe dyscrasia.

Exclusion Criteria:

  1. Patients with leptomeningeal metastasis from unknown primary tumor;
  2. Patients who had received whole brain radiotherapy in the past 10 months;
  3. Patients who had accepted systemic chemotherapy within two weeks, or molecular targeted therapy less than two weeks;
  4. Patients with poor compliance, or for other reasons, the researchers considered unsuitable to participate in this clinical study.

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: Group 1,Intra-pemetrexed, radiotherapy
The treatment regimen consisted of intrathecal chemotherapy (via lumbar puncture, pemetrexed 10 mg, plus dexamethasone 5 mg, once per week, 5-8 times, 4-7 weeks in total) and radiotherapy. Radiotherapy consisted of fractionated, conformal radiation given at a daily dose of 2 Gy. The planning volume consisted of sites of symptomatic disease, bulky disease observed on magnetic resonance imaging, including the whole brain and basis cranii received 40 Gy in 20 fractions, 4 weeks in total, and/or segment of spinal canal received 40-50 Gy.
Radiation: Radiotherapy
The sites of symptomatic disease, bulky disease observed on MRI, including the whole brain and basis cranii, 40 Gy in 20 fractions;and/or segment of spinal canal received 40-50 Gy in 20-25 fractions.
Drug: Pemetrexed
Pemetrexed, 10 mg,intrathecal injection, plus dexamethasone 5 mg, once per week, 5 to 8 times, 4 to 7 weeks in total.
Drug: Dexamethasone
Dexamethasone, 5 mg, intrathecal injection, simultaneously with pemetrexed, once per week, 5 to 8 times, 4 to 7 weeks in total.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence of treatment-related adverse events
Time Frame: The evaluation was performed at 3 months after the end of treatment or when patient died.
The incidence of treatment-related adverse events were measured for determing tolerability and safety. Adverse events (AEs) are evaluated according to the Common Terminology Criteria for Adverse Events (CTCAE, version 4.03). Events of grade 3-5 are defined as moderate and severe adverse events.
The evaluation was performed at 3 months after the end of treatment or when patient died.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Clinical response rate
Time Frame: The evaluation was performed at 3 months after the end of treatment or when patient died.
The RANO proposal for response criteria of leptomeningeal metastasis was used to assess the clinical response in this study.
The evaluation was performed at 3 months after the end of treatment or when patient died.
Overall survival
Time Frame: The evaluation was performed at least 7 months after leptomeningeal metastasis diagnosis or until death.
Survival time was recorded since the date of patient enrollment. All patients were followed up until death or the end of the study.
The evaluation was performed at least 7 months after leptomeningeal metastasis diagnosis or until death.
Neurological progression-free survival (NPFS)
Time Frame: All patients were followed up at least 6 months, and the evaluation of NPFS was performed from the beginning of treatment until the date of first documented neurological progression or date of death from any cause, whichever came first.
NPFS was defined as time from the start of treatment until neurological progression or death. The neurological progression was determined based on the RANO proposal evaluation criteria which have been established and published on Neuro Oncol.
All patients were followed up at least 6 months, and the evaluation of NPFS was performed from the beginning of treatment until the date of first documented neurological progression or date of death from any cause, whichever came first.

Collaborators and Investigators

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

Sponsor

The First Hospital of Jilin University

Investigators

  • Principal Investigator: Zhenyu Pan, Professor, The First Hospital of Jilin University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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)

April 12, 2018

Primary Completion (Actual)

January 15, 2019

Study Completion (Actual)

July 30, 2019

Study Registration Dates

First Submitted

March 31, 2018

First Submitted That Met QC Criteria

April 23, 2018

First Posted (Actual)

April 25, 2018

Study Record Updates

Last Update Posted (Actual)

December 26, 2019

Last Update Submitted That Met QC Criteria

December 23, 2019

Last Verified

December 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • IPLM

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

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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