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

This study is currently recruiting participants.
Verified March 2017 by Zhenyu Pan, First Hospital of Jilin University
Sponsor:
ClinicalTrials.gov Identifier:
NCT03082144
First Posted: March 17, 2017
Last Update Posted: March 17, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Information provided by (Responsible Party):
Zhenyu Pan, First Hospital of Jilin University
  Purpose
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.

Condition Intervention Phase
Leptomeningeal Metastasis Drug: MTX Drug: Ara-C Radiation: Radiotherapy Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Involved-field Radiotherapy Combined With Concurrent Intrathecal-MTX Versus Intrathecal-Ara-C for Leptomeningeal Metastases From Solid Tumor: A Randomized Phase II Clinical Trial

Resource links provided by NLM:


Further study details as provided by Zhenyu Pan, First Hospital of Jilin University:

Primary Outcome Measures:
  • 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. ]
    In the previous study, investigators established the criteria of evaluation for clinical response based on improvement of neurologic symptoms/signs and changes of KPS. The clinical response was evaluated by at least two experienced neuro-oncologists. The evaluation consists of 5 layers, including complete response (CR), obvious response (OR), partial response (PR), stable disease (SD) and progressive disease (PD). Clinical response was defined as continuous presence of CR, OR or PR within an interval of at least 1 week. Stable disease (SD) and progressive disease (PD) were defined as ineffective.


Secondary Outcome Measures:
  • Time-to-Progression (TTP) [ Time Frame: At least 7 months after LM diagnosis or until death. ]
    From time of patients defined as clinical response, till LM-relative neurological symptoms or signs relapse or progress.

  • 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 3.0). Events of grade 3-5 was defined as moderate and severe adverse events.

  • Overall survival(OS) [ Time Frame: At least 7 months after LM diagnosis or until death. ]
    Survival time was recorded since the date of LM diagnosis. All patients were followed up until death or the end of the study.


Estimated Enrollment: 70
Actual Study Start Date: February 1, 2017
Estimated Study Completion Date: February 2019
Estimated Primary Completion Date: June 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: 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.
Drug: Ara-C
Ara-C 50mg,via lumbar puncture,once per week, 4 weeks in total
Other Name: 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.

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. In the investigator's previous study, criteria of evaluation for clinical response that has been established was based on improvement of neurologic symptoms/signs and changes of karnofsky performance status(KPS). The criteria were proved as effective method for the evaluation of prognosis. The method was used to assess the clinical response in this study.
  Eligibility

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03082144


Contacts
Contact: Zhenyu Pan, Professor +8615804302753 dr-zypan@163.com
Contact: Guozi Yang, Professor +8615804302755 guoziyang_1982@163.com

Locations
China, Jilin
The First Hospital of Jilin University Recruiting
Changchun, Jilin, China, 130021
Contact: Zhenyu Pan, Professor    +8615804302753    dr-zypan@163.com   
Contact: Guozi Yang, Professor    +8615804302755    guoziyang_1982@163.com   
Sponsors and Collaborators
First Hospital of Jilin University
Investigators
Principal Investigator: Zhenyu Pan, Professor First Hospital of Jilin University
  More Information

Publications:

Responsible Party: Zhenyu Pan, Professor, First Hospital of Jilin University
ClinicalTrials.gov Identifier: NCT03082144     History of Changes
Other Study ID Numbers: MVARTICLM
First Submitted: March 5, 2017
First Posted: March 17, 2017
Last Update Posted: March 17, 2017
Last Verified: March 2017

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Neoplasm Metastasis
Meningeal Carcinomatosis
Neoplastic Processes
Neoplasms
Pathologic Processes
Meningeal Neoplasms
Central Nervous System Neoplasms
Nervous System Neoplasms
Neoplasms by Site
Nervous System Diseases
Cytarabine
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Antiviral Agents
Anti-Infective Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs