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

Leptomeningeal Metastasis Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03082144
• Other study ID #: MVARTICLM
• Status: Completed
• Phase: Phase 2
• Start date: February 1, 2017
• Est. completion date: December 30, 2018

Study information

• Verified date: July 2019
• Source: First Hospital of Jilin University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 53
• Est. completion date: December 30, 2018
• Est. primary completion date: May 30, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Leptomeningeal Metastasis
• Meningeal Carcinomatosis
• Neoplasm Metastasis

Intervention

Drug:
• MTX
MTX 15 mg,via lumbar puncture,once per week, 4 weeks in total
• Ara-C
Ara-C 50mg,via lumbar puncture,once per week, 4 weeks in total

Radiation:
• 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.

Locations

Country	Name	City	State
China	The First Hospital of Jilin University	Changchun	Jilin

Sponsors (1)

Lead Sponsor	Collaborator
First Hospital of Jilin University

Country where clinical trial is conducted

China, 

References & Publications (9)

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

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

Mack F, Baumert BG, Schäfer 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. Review. — View 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 — View 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 f — View 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. Review. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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.	At least 7 months after LM diagnosis or until death.
Secondary	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.	At least 7 months after LM diagnosis or until death.