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

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

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

Brief Summary: 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.

Detailed Summary: 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.
Sponsor: First Hospital of Jilin University

Current Primary Outcome: 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.


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • 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.


Original Secondary Outcome: Same as current

Information By: First Hospital of Jilin University

Dates:
Date Received: March 5, 2017
Date Started: February 1, 2017
Date Completion: February 2019
Last Updated: March 10, 2017
Last Verified: March 2017