Concurrent Involved-field Radiotherapy and Intrathecal Chemotherapy for Leptomeningeal Metastases From Solid Tumors

July 30, 2019 updated by: Zhenyu Pan, The First Hospital of Jilin University

Involved-field Radiotherapy Combined With Concurrent Intrathecal-MTX Versus Intrathecal-Ara-C for Leptomeningeal Metastases From Solid Tumor: A Randomized Phase II Clinical Trial

It has been proved that concurrent radiotherapy (RT) and intrathecal methotrexate (MTX) for leptomeningeal metastases (LM) from solid tumors with adverse prognostic factors showed great effectiveness and safety. Cytarabine(Ara-C) is another agent which is commonly used for intrathecal chemotherapy. The purpose of the study is to observe the effectiveness and safety of concurrent RT and intrathecal chemotherapy for LM from solid tumors. In addition, the effectiveness of these two types of agents (MTX and Ara-C) in the concurrent chemo-radiotherapy will be compared in this study. This is a randomized controlled, parallel group, and phase II clinical trial. The object of this study is newly diagnosis patients with leptomeningeal metastases from solid tumors, who will accept the treatment of involved-field RT combined with concurrent intrathecal-MTX or intrathecal-Ara-C, respectively. Major endpoint is clinical response rate. Secondary endpoints are time to progression,severe adverse events and overall survival.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

The patients were randomly divided into two groups, who will accept the treatment of involved-field RT combined with concurrent intrathecal-MTX or intrathecal-Ara-C, respectively. Concomitant regimen consisted of intrathecal chemotherapy (via lumbar puncture, MTX 15 mg, plus dexamethasone 5 mg, or Ara-C 50mg, plus dexamethasone 5 mg, once per week, 4 weeks in total) and RT. RT 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 MRI, including the whole brain and basis cranii received 40 Gy in 20 fractions and/or segment of spinal canal received 40-50 Gy. The RANO proposal for response criteria of LM disease was used to assess the clinical response in this study.

Study Type

Interventional

Enrollment (Actual)

53

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 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

18 years to 75 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 cytology or neuroimaging, or patients who got the clinical diagnosis by combining with the history of cancer, clinical manifestation, cerebrospinal fluid examination, neuroimaging etc;
  2. Patients who have been diagnosed as malignant solid tumor with definite pathologic type, excluding hematological malignancies (e.g., leukemia and lymphoma) or primary brain tumors;
  3. No severe abnormal liver and kidney function; WBC≥2500/mm3, Plt≥60000/mm3;
  4. No other severe chronic diseases;
  5. No history of severe nervous system disease;
  6. No severe dyscrasia;
  7. Signed informed consent form.

Exclusion Criteria:

  1. Patients with leptomeningeal metastasis from unknown primary tumor;
  2. Patients who had received radiotherapy to the brain in the past 6 months;
  3. Patients who had accepted systemic chemotherapy within one month before the treatment, or molecular targeted therapy less than 3 months;
  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: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Group 1: RT-Intra-MTX
Intrathecal chemotherapy: MTX 15 mg, plus dexamethasone 5 mg, via lumbar puncture,once per week, 4 weeks in total.
Drug: MTX
MTX 15 mg,via lumbar puncture,once per week, 4 weeks in total
Other Names:
  • Intrathecal chemotherapy
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.
Experimental: Group2: RT-Intra-Ara-C
Intrathecal chemotherapy:Ara-C 50 mg, plus dexamethasone 5 mg, via lumbar puncture, once per week, 4 weeks in total.
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: Ara-C
Ara-C 50mg,via lumbar puncture,once per week, 4 weeks in total
Other Names:
  • Intrathecal chemotherapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Clinical Response Rate (CRR)
Time Frame: The evaluation was performed once per week from the beginning of LM-related therapy, till 4 weeks later after concomitant therapy.
The RANO proposal for response criteria of LM disease was used to assess the clinical response in this study.
The evaluation was performed once per week from the beginning of LM-related therapy, till 4 weeks later after concomitant therapy.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence of severe adverse events (SAE)
Time Frame: At least 7 months after LM diagnosis or until death.
Adverse events (AEs) were evaluated according to the Common Terminology Criteria for Adverse Events (CTCAE, version 4.03). Events of grade 3-5 was defined as moderate and severe adverse events.
At least 7 months after LM diagnosis or until death.
Overall survival(OS)
Time Frame: At least 7 months after LM 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.
At least 7 months after LM diagnosis or until death.

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)

February 1, 2017

Primary Completion (Actual)

May 30, 2018

Study Completion (Actual)

December 30, 2018

Study Registration Dates

First Submitted

March 5, 2017

First Submitted That Met QC Criteria

March 10, 2017

First Posted (Actual)

March 17, 2017

Study Record Updates

Last Update Posted (Actual)

August 1, 2019

Last Update Submitted That Met QC Criteria

July 30, 2019

Last Verified

July 1, 2019

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • MVARTICLM

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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