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

Phase 2

Completed

• Conditions: Leptomeningeal Metastasis
• Interventions: Drug: MTX; Drug: Ara-C; Radiation: Radiotherapy

• Registration Number: NCT03082144
• Lead Sponsor: The First Hospital of Jilin University

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 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 Timeline

• Study Start: 2017-02-01
• Study First Submitted: 2017-03-05
• Study First Submitted QC: 2017-03-10
• Study First Posted: 2017-03-17
• Primary Completion: 2018-05-30
• Study Completion: 2018-12-30
• Status Verified: 2019-07
• Last Update Submitted: 2019-07-30
• Last Update Posted: 2019-08-01

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 53

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Group 1: RT-Intra-MTX	MTX	Intrathecal chemotherapy: MTX 15 mg, plus dexamethasone 5 mg, via lumbar puncture,once per week, 4 weeks in total.
Group 1: RT-Intra-MTX	Radiotherapy	Intrathecal chemotherapy: MTX 15 mg, plus dexamethasone 5 mg, via lumbar puncture,once per week, 4 weeks in total.
Group2: RT-Intra-Ara-C	Ara-C	Intrathecal chemotherapy:Ara-C 50 mg, plus dexamethasone 5 mg, via lumbar puncture, once per week, 4 weeks in total.
Group2: RT-Intra-Ara-C	Radiotherapy	Intrathecal chemotherapy:Ara-C 50 mg, plus dexamethasone 5 mg, via lumbar puncture, once per week, 4 weeks in total.

Primary Outcome Measures

Name	Time	Method
Clinical Response Rate (CRR)	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.

Secondary Outcome Measures

Name	Time	Method
Incidence of severe adverse events (SAE)	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.
Overall survival(OS)	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.

Trial Locations

Locations (1)

The First Hospital of Jilin University; 🇨🇳 Changchun, Jilin, China