Leptomeningeal MetastasisPhase 2NCT03082144
Concurrent Involved-field Radiotherapy and Intrathecal Chemotherapy for Leptomeningeal Metastases From Solid Tumors
A Phase 2 study testing MTX, Ara-C and Radiotherapy in people with Leptomeningeal Metastasis, run by The First Hospital of Jilin University at 1 site in China.
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. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Leptomeningeal Metastasis
- What is being tested?
- MTX, Ara-C and Radiotherapy
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 53 participants
- Where
- 1 siteChina
- Study dates
- 1 Feb 2017to 30 Dec 2018
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
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
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.
Read the 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.
- Conditions
- Leptomeningeal Metastasis
- Being tested
- MTX, Ara-C, Radiotherapy
- Medical subject headings
- Meningeal Carcinomatosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MTXDrug
Also called Intrathecal chemotherapy
MTX 15 mg,via lumbar puncture,once per week, 4 weeks in total
Ara-CDrug
Also called Intrathecal chemotherapy
Ara-C 50mg,via lumbar puncture,once per week, 4 weeks in total
RadiotherapyRadiation
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: Ara-C; Radiation: Radiotherapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Clinical Response Rate (CRR)
The RANO proposal for response criteria of LM disease was used to assess the clinical response in this study.
Measured: 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)
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.
Measured: At least 7 months after LM diagnosis or until death.
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.
Measured: At least 7 months after LM diagnosis or until death.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Mar 2017
- Study start1 Feb 2017
- Primary completion30 May 2018
- Study completion30 Dec 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (9)Papers the sponsor has linked to this study.
- Other trials for Leptomeningeal MetastasisStudies of the same condition, open and under way.
- More trials run by The First Hospital of Jilin UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 53 participants (actual)
Sponsor and investigators
- Lead sponsor
- The First Hospital of Jilin University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Zhenyu Pan, The First Hospital of Jilin University
- Investigators
- Zhenyu Pan, Professor, Principal investigator, The First Hospital of Jilin University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03082144
- Sponsor's protocol ID
- MVARTICLM
- Status last verified
- Jul 2019
- First submitted
- 5 Mar 2017
- Last updated
- 1 Aug 2019
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
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.
PubMed 27243238Pan 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.
PubMed 25850010Pan 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.
PubMed 24893802Pan 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.
PubMed 25142885Mack 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.
PubMed 26827696Grewal 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.
PubMed 21874597Chamberlain MC. Leptomeningeal metastasis. Curr Opin Oncol. 2010 Nov;22(6):627-35. doi: 10.1097/CCO.0b013e32833de986.
PubMed 20689429Chamberlain MC. Leptomeningeal metastasis. Curr Opin Neurol. 2009 Dec;22(6):665-74. doi: 10.1097/WCO.0b013e3283322a92.
PubMed 19738466Le 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.
PubMed 23717798
Study at a glance
From the registry record, last updated by the sponsor on 1 Aug 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03082144
- Acronym / sponsor ID
- MVARTICLM
- Conditions
- Leptomeningeal Metastasis
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 53 participants (actual)
- Lead sponsor
- The First Hospital of Jilin UniversityUniversity, hospital or other
- Study start
- 1 Feb 2017 (actual)
- Primary completion
- 30 May 2018 (actual)
- Study completion
- 30 Dec 2018 (actual)
- First posted
- 17 Mar 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Group 1: RT-Intra-MTX | Active comparator | Drug: MTX, Radiation: RadiotherapyIntrathecal chemotherapy: MTX 15 mg, plus dexamethasone 5 mg, via lumbar puncture,once per week, 4 weeks in total. |
| Group2: RT-Intra-Ara-C | Experimental | Drug: Ara-C, Radiation: RadiotherapyIntrathecal chemotherapy:Ara-C 50 mg, plus dexamethasone 5 mg, via lumbar puncture, once per week, 4 weeks in total. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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;
Key exclusion criteria (4 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MTXAlso: Intrathecal chemotherapyMTX 15 mg,via lumbar puncture,once per week, 4 weeks in total | Drug | Group 1: RT-Intra-MTX |
| Ara-CAlso: Intrathecal chemotherapyAra-C 50mg,via lumbar puncture,once per week, 4 weeks in total | Drug | Group2: RT-Intra-Ara-C |
| RadiotherapyThe 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. | Radiation | Group 1: RT-Intra-MTX, Group2: RT-Intra-Ara-C |
Primary outcome
Clinical Response Rate (CRR)
Time frame: 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.
2 secondary outcomes
Incidence of severe adverse events (SAE)
Time frame: At least 7 months after LM diagnosis or until death.
Overall survival(OS)
Time frame: At least 7 months after LM diagnosis or until death.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Aug 2019.
- Results publication: PubMed 27243238Pan 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 publication: PubMed 25850010Pan 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 publication: PubMed 24893802Pan 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 publication: PubMed 25142885Pan 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 publication: PubMed 26827696Mack 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 publication: PubMed 21874597Grewal 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 publication: PubMed 20689429Chamberlain MC. Leptomeningeal metastasis. Curr Opin Oncol. 2010 Nov;22(6):627-35. doi: 10.1097/CCO.0b013e32833de986.
- Results publication: PubMed 19738466Chamberlain MC. Leptomeningeal metastasis. Curr Opin Neurol. 2009 Dec;22(6):665-74. doi: 10.1097/WCO.0b013e3283322a92.
- Results publication: PubMed 23717798Le 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Zhenyu Pan, Professor principal investigator
The First Hospital of Jilin University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing MTX, Ara-C and Radiotherapy in people with Leptomeningeal Metastasis, run by The First Hospital of Jilin University at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 1 Aug 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Clinical Response Rate (CRR) (time frame: The evaluation was performed once per week from the beginning of LM-related therapy, till 4 weeks later after concomitant therapy.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03082144, which also lists 9 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Aug 2019.