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

NCT03082144 | Completed Phase 2 DMC

• 1 other identifier: MVARTICLM
• Study Type: interventional
• Target: 53
• Locations: 1 country
• Sites: 1

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.

Conditions

Leptomeningeal Metastasis

Outcome Measures

Primary Outcomes (1)

• Clinical Response Rate (CRR)

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

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

Secondary Outcomes (2)

• Incidence of severe adverse events (SAE)

  At least 7 months after LM diagnosis or until death.

• Overall survival(OS)

  At least 7 months after LM diagnosis or until death.

Study Arms (2)

Group 1: RT-Intra-MTX

ACTIVE COMPARATOR

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

Drug: MTX; Radiation: Radiotherapy

Group2: RT-Intra-Ara-C

EXPERIMENTAL

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

Drug: Ara-C; Radiation: Radiotherapy

Interventions

MTX DRUG

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

Also known as: Intrathecal chemotherapy

Group 1: RT-Intra-MTX

Ara-C DRUG

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

Also known as: Intrathecal chemotherapy

Group2: RT-Intra-Ara-C

Radiotherapy 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.

Group 1: RT-Intra-MTX; Group2: RT-Intra-Ara-C

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• The First Hospital of Jilin University: lead

Study Sites (1)

The First Hospital of Jilin University

Changchun, Jilin, 130021, China

Location

Related Publications (9)

• 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.

  PMID: 27243238 RESULT

• 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.

  PMID: 25850010 RESULT

• 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.

  PMID: 24893802 RESULT

• 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.

  PMID: 25142885 RESULT

• 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.

  PMID: 26827696 RESULT

• 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.

  PMID: 21874597 RESULT

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

  PMID: 20689429 RESULT

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

  PMID: 19738466 RESULT

• 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.

  PMID: 23717798 RESULT

MeSH Terms

Conditions

Meningeal Carcinomatosis

Interventions

Cytarabine; Radiotherapy

Condition Hierarchy (Ancestors)

Meningeal Neoplasms; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Therapeutics

Study Officials

• Zhenyu Pan, Professor

  The First Hospital of Jilin University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: March 5, 2017
• First Posted: March 17, 2017
• Study Start: February 1, 2017
• Primary Completion: May 30, 2018
• Study Completion: December 30, 2018
• Last Updated: August 1, 2019

Record last verified: 2019-07

Locations

CN (1)