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

NCT ID: NCT03082144

Last Updated: 2019-08-01

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

53 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-02-01

Study Completion Date

2018-12-30

Brief Summary

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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

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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.

Conditions

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Leptomeningeal Metastasis

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Group 1: RT-Intra-MTX

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

Group Type ACTIVE_COMPARATOR

MTX

Intervention Type DRUG

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

Radiotherapy

Intervention Type RADIATION

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.

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.

Group Type EXPERIMENTAL

Ara-C

Intervention Type DRUG

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

Radiotherapy

Intervention Type RADIATION

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.

Interventions

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MTX

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

Intervention Type DRUG

Ara-C

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

Intervention Type DRUG

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.

Intervention Type RADIATION

Other Intervention Names

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Intrathecal chemotherapy Intrathecal chemotherapy

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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The First Hospital of Jilin University

OTHER

Sponsor Role lead

Responsible Party

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Zhenyu Pan

Professor

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Zhenyu Pan, Professor

Role: PRINCIPAL_INVESTIGATOR

The First Hospital of Jilin University

Locations

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The First Hospital of Jilin University

Changchun, Jilin, China

Site Status

Countries

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China

References

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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.

Reference Type RESULT
PMID: 27243238 (View on PubMed)

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.

Reference Type RESULT
PMID: 25850010 (View on PubMed)

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.

Reference Type RESULT
PMID: 24893802 (View on PubMed)

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.

Reference Type RESULT
PMID: 25142885 (View on PubMed)

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.

Reference Type RESULT
PMID: 26827696 (View on PubMed)

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.

Reference Type RESULT
PMID: 21874597 (View on PubMed)

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

Reference Type RESULT
PMID: 20689429 (View on PubMed)

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

Reference Type RESULT
PMID: 19738466 (View on PubMed)

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.

Reference Type RESULT
PMID: 23717798 (View on PubMed)

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

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MVARTICLM

Identifier Type: -

Identifier Source: org_study_id

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