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

Primary Purpose

Leptomeningeal Metastasis

Status

Completed

Phase

Phase 2

Locations

China

Study Type

Interventional

Intervention

MTX

Ara-C

Radiotherapy

About this trial

This is an interventional treatment trial for Leptomeningeal Metastasis

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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;
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;
No severe abnormal liver and kidney function; WBC≥2500/mm3, Plt≥60000/mm3;
No other severe chronic diseases;
No history of severe nervous system disease;
No severe dyscrasia;
Signed informed consent form.

Exclusion Criteria:

Patients with leptomeningeal metastasis from unknown primary tumor;
Patients who had received radiotherapy to the brain in the past 6 months;
Patients who had accepted systemic chemotherapy within one month before the treatment, or molecular targeted therapy less than 3 months;
Patients with poor compliance, or for other reasons, the researchers considered unsuitable to participate in this clinical study.

Sites / Locations

The First Hospital of Jilin University

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

Group 1: RT-Intra-MTX

Group2: RT-Intra-Ara-C

Arm Description

Intrathecal chemotherapy: MTX 15 mg, plus dexamethasone 5 mg, via lumbar puncture,once per week, 4 weeks in total.

Intrathecal chemotherapy:Ara-C 50 mg, plus dexamethasone 5 mg, via lumbar puncture, once per week, 4 weeks in total.

Outcomes

Primary Outcome Measures

Clinical Response Rate (CRR)

The RANO proposal for response criteria of LM disease was used to assess the clinical response in this study.

Secondary Outcome Measures

Incidence of severe adverse events (SAE)

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)

Survival time was recorded since the date of patient enrollment. All patients were followed up until death or the end of the study.

Full Information

NCT ID

NCT03082144

First Posted

March 5, 2017

Last Updated

July 30, 2019

Sponsor

The First Hospital of Jilin University

1. Study Identification

Unique Protocol Identification Number

NCT03082144

Brief Title

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

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

Study Type

Interventional

2. Study Status

Record Verification Date

July 2019

Overall Recruitment Status

Completed

Study Start Date

February 1, 2017 (Actual)

Primary Completion Date

May 30, 2018 (Actual)

Study Completion Date

December 30, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

The First Hospital of Jilin University

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Leptomeningeal Metastasis

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

53 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Group 1: RT-Intra-MTX

Arm Type

Active Comparator

Arm Description

Intrathecal chemotherapy: MTX 15 mg, plus dexamethasone 5 mg, via lumbar puncture,once per week, 4 weeks in total.

Arm Title

Group2: RT-Intra-Ara-C

Arm Type

Experimental

Arm Description

Intrathecal chemotherapy:Ara-C 50 mg, plus dexamethasone 5 mg, via lumbar puncture, once per week, 4 weeks in total.

Intervention Type

Drug

Intervention Name(s)

MTX

Other Intervention Name(s)

Intrathecal chemotherapy

Intervention Description

MTX 15 mg,via lumbar puncture,once per week, 4 weeks in total

Intervention Type

Drug

Intervention Name(s)

Ara-C

Other Intervention Name(s)

Intrathecal chemotherapy

Intervention Description

Ara-C 50mg,via lumbar puncture,once per week, 4 weeks in total

Intervention Type

Radiation

Intervention Name(s)

Radiotherapy

Intervention Description

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.

Primary Outcome Measure Information:

Title

Clinical Response Rate (CRR)

Description

The RANO proposal for response criteria of LM disease was used to assess the clinical response in this study.

Time Frame

The evaluation was performed once per week from the beginning of LM-related therapy, till 4 weeks later after concomitant therapy.

Secondary Outcome Measure Information:

Title

Incidence of severe adverse events (SAE)

Description

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.

Time Frame

At least 7 months after LM diagnosis or until death.

Title

Overall survival(OS)

Description

Survival time was recorded since the date of patient enrollment. All patients were followed up until death or the end of the study.

Time Frame

At least 7 months after LM diagnosis or until death.

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

75 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 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; 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; No severe abnormal liver and kidney function; WBC≥2500/mm3, Plt≥60000/mm3; No other severe chronic diseases; No history of severe nervous system disease; No severe dyscrasia; Signed informed consent form. Exclusion Criteria: Patients with leptomeningeal metastasis from unknown primary tumor; Patients who had received radiotherapy to the brain in the past 6 months; Patients who had accepted systemic chemotherapy within one month before the treatment, or molecular targeted therapy less than 3 months; Patients with poor compliance, or for other reasons, the researchers considered unsuitable to participate in this clinical study.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Zhenyu Pan, Professor

Organizational Affiliation

The First Hospital of Jilin University

Official's Role

Principal Investigator

Facility Information:

Facility Name

The First Hospital of Jilin University

City

Changchun

State/Province

Jilin

ZIP/Postal Code

130021

Country

China

12. IPD Sharing Statement

Citations:

PubMed Identifier

27243238

Citation

Pan Z, Yang G, He H, Zhao G, Yuan T, Li Y, Shi W, Gao P, Dong L, Li Y. Concurrent radiotherapy and intrathecal methotrexate for treating leptomeningeal metastasis from solid tumors with adverse prognostic factors: A prospective and single-arm study. Int J Cancer. 2016 Oct 15;139(8):1864-72. doi: 10.1002/ijc.30214. Epub 2016 Jun 30.

Results Reference

result

PubMed Identifier

25850010

Citation

Pan Z, Yang G, Wang Y, He H, Pang X, Gao Y, Shi W, Li Y, Dong L, Song Y. Thinprep plus Papanicolaou stain method is more sensitive than cytospin-coupled Wright Giems stain method in cerebrospinal fluid cytology for diagnosis of leptomeningeal metastasis from solid tumors. PLoS One. 2015 Apr 7;10(4):e0122016. doi: 10.1371/journal.pone.0122016. eCollection 2015.

Results Reference

result

PubMed Identifier

24893802

Citation

Pan Z, Yang G, Yuan T, Pang X, Wang Y, Qu L, Dong L. Leptomeningeal metastasis from hepatocellular carcinoma with other unusual metastases: a case report. BMC Cancer. 2014 Jun 3;14:399. doi: 10.1186/1471-2407-14-399.

Results Reference

result

PubMed Identifier

25142885

Citation

Pan Z, Yang G, Wang Y, Yuan T, Gao Y, Dong L. Leptomeningeal metastases from a primary central nervous system melanoma: a case report and literature review. World J Surg Oncol. 2014 Aug 20;12:265. doi: 10.1186/1477-7819-12-265.

Results Reference

result

PubMed Identifier

26827696

Citation

Mack F, Baumert BG, Schafer N, Hattingen E, Scheffler B, Herrlinger U, Glas M. Therapy of leptomeningeal metastasis in solid tumors. Cancer Treat Rev. 2016 Feb;43:83-91. doi: 10.1016/j.ctrv.2015.12.004. Epub 2015 Dec 24.

Results Reference

result

PubMed Identifier

21874597

Citation

Grewal J, Saria MG, Kesari S. Novel approaches to treating leptomeningeal metastases. J Neurooncol. 2012 Jan;106(2):225-34. doi: 10.1007/s11060-011-0686-2. Epub 2011 Aug 28.

Results Reference

result

PubMed Identifier

20689429

Citation

Chamberlain MC. Leptomeningeal metastasis. Curr Opin Oncol. 2010 Nov;22(6):627-35. doi: 10.1097/CCO.0b013e32833de986.

Results Reference

result

PubMed Identifier

19738466

Citation

Chamberlain MC. Leptomeningeal metastasis. Curr Opin Neurol. 2009 Dec;22(6):665-74. doi: 10.1097/WCO.0b013e3283322a92.

Results Reference

result

PubMed Identifier

23717798

Citation

Le Rhun E, Taillibert S, Chamberlain MC. Carcinomatous meningitis: Leptomeningeal metastases in solid tumors. Surg Neurol Int. 2013 May 2;4(Suppl 4):S265-88. doi: 10.4103/2152-7806.111304. Print 2013.

Results Reference

result

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

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