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Concurrent Intrathecal-pemetrexed and Involved-field Radiotherapy for Leptomeningeal Metastasis From Solid Tumors

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ClinicalTrials.gov Identifier: NCT03507244
Recruitment Status : Completed
First Posted : April 25, 2018
Last Update Posted : December 26, 2019
Sponsor:
Information provided by (Responsible Party):
Zhenyu Pan, The First Hospital of Jilin University

Brief Summary:
Intrathecal chemotherapy is one of the most important treatment modalities for leptomeningeal metastasis of solid tumors. In the previous retrospective study, it has been proved that concurrent radiotherapy and intrathecal methotrexate for leptomeningeal metastasis from solid tumors with adverse prognostic factors showed great effectiveness and safety. The preliminary results of investigators' current prospective clinical study (Involved-field Radiotherapy Combined With Concurrent Intrathecal-methotrexate Versus Intrathecal-Ara-C for Leptomeningeal Metastases From Solid Tumor: A Randomized Phase II Clinical Trial. ClinicalTrials.gov identification number: NCT03082144) also showed that the regimen of concurrent intrathecal chemotherapy and radiotherapy may serve as an optimal therapeutic option for treatment of leptomeningeal metastases from solid tumors. Pemetrexed is a newer multitargeted antifolate which has shown activity in various tumors. In investigators' current study (Intrathecal Pemetrexed for Recurrent Leptomeningeal Metastasis From Non-small Cell Lung Cancer: A Prospective Pilot Clinical Trial. ClinicalTrials.gov identification number: NCT03101579), the regimen of intrathecal pemetrexed with folic acid and vitamin B12 supplementation may provide higher effectiveness and safety for recurrent leptomeningeal metastasis from non-small cell lung cancer. Therefore, the purpose of the study is to evaluate the tolerability, safety and effectiveness of intrathecal pemetrexed combined with involved-field radiotherapy as the first line treatment in patients with leptomeningeal metastases from malignant solid tumors.

Condition or disease Intervention/treatment Phase
Leptomeningeal Metastasis Drug: Pemetrexed Drug: Dexamethasone Radiation: Radiotherapy Phase 1 Phase 2

Detailed Description:
This study is a single arm, open clinical trial. Consecutive patients with leptomeningeal metastases from malignant solid tumors are enrolled into this study. Concomitant regimen consisted of intrathecal chemotherapy (via lumbar puncture, pemetrexed 10 mg, plus dexamethasone 5 mg, once per week, 5 to 8 times, 4 to 7 weeks in total) and radiotherapy. Radiotherapy 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 magnetic resonance imaging(MRI), including the whole brain and basis cranii received 40 Gy in 20 fractions, 4 weeks in total, and/or segment of spinal canal received 40-50 Gy. The RANO proposal for response criteria of leptomeningeal metastasis was used to assess the clinical response in this study.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 34 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Intrathecal-pemetrexed Combined With Concurrent Involved-field Radiotherapy for Leptomeningeal Metastasis From Solid Tumor: a Phase I/II Clinical Trial
Actual Study Start Date : April 12, 2018
Actual Primary Completion Date : January 15, 2019
Actual Study Completion Date : July 30, 2019

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Arm Intervention/treatment
Experimental: Group 1,Intra-pemetrexed, radiotherapy
The treatment regimen consisted of intrathecal chemotherapy (via lumbar puncture, pemetrexed 10 mg, plus dexamethasone 5 mg, once per week, 5-8 times, 4-7 weeks in total) and radiotherapy. Radiotherapy 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 magnetic resonance imaging, including the whole brain and basis cranii received 40 Gy in 20 fractions, 4 weeks in total, and/or segment of spinal canal received 40-50 Gy.
Drug: Pemetrexed
Pemetrexed, 10 mg,intrathecal injection, plus dexamethasone 5 mg, once per week, 5 to 8 times, 4 to 7 weeks in total.

Drug: Dexamethasone
Dexamethasone, 5 mg, intrathecal injection, simultaneously with pemetrexed, once per week, 5 to 8 times, 4 to 7 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.




Primary Outcome Measures :
  1. Incidence of treatment-related adverse events [ Time Frame: The evaluation was performed at 3 months after the end of treatment or when patient died. ]
    The incidence of treatment-related adverse events were measured for determing tolerability and safety. Adverse events (AEs) are evaluated according to the Common Terminology Criteria for Adverse Events (CTCAE, version 4.03). Events of grade 3-5 are defined as moderate and severe adverse events.


Secondary Outcome Measures :
  1. Clinical response rate [ Time Frame: The evaluation was performed at 3 months after the end of treatment or when patient died. ]
    The RANO proposal for response criteria of leptomeningeal metastasis was used to assess the clinical response in this study.

  2. Overall survival [ Time Frame: The evaluation was performed at least 7 months after leptomeningeal metastasis diagnosis or until death. ]
    Survival time was recorded since the date of patient enrollment. All patients were followed up until death or the end of the study.

  3. Neurological progression-free survival (NPFS) [ Time Frame: All patients were followed up at least 6 months, and the evaluation of NPFS was performed from the beginning of treatment until the date of first documented neurological progression or date of death from any cause, whichever came first. ]
    NPFS was defined as time from the start of treatment until neurological progression or death. The neurological progression was determined based on the RANO proposal evaluation criteria which have been established and published on Neuro Oncol.



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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Patients who have been definitely diagnosed as leptomeningeal metastasis according to cerebrospinal fluid (CSF) cytology, or patients who got the clinical diagnosis by combining history of cancer, neuroimaging, clinical manifestation, and CSF examination, etc.
  2. Patients who have been diagnosed as malignant solid tumor with definite pathologic type, excluding hematological malignancies (e.g., leukemia and lymphoma) or intracranial germ cell tumors;
  3. No severe abnormal liver function; normal kidney function; WBC≥4000/mm3, Plt≥110000/mm3;
  4. No other severe chronic diseases;
  5. No severe dyscrasia.

Exclusion Criteria:

  1. Patients with leptomeningeal metastasis from unknown primary tumor;
  2. Patients who had received whole brain radiotherapy in the past 10 months;
  3. Patients who had accepted systemic chemotherapy within two weeks, or molecular targeted therapy less than two weeks;
  4. Patients with poor compliance, or for other reasons, the researchers considered unsuitable to participate in this clinical study.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03507244


Locations
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China, Jilin
The First Hospital of Jilin University
Changchun, Jilin, China, 130021
Sponsors and Collaborators
The First Hospital of Jilin University
Investigators
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Principal Investigator: Zhenyu Pan, Professor The First Hospital of Jilin University
Publications of Results:

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Zhenyu Pan, Professor, The First Hospital of Jilin University
ClinicalTrials.gov Identifier: NCT03507244    
Other Study ID Numbers: IPLM
First Posted: April 25, 2018    Key Record Dates
Last Update Posted: December 26, 2019
Last Verified: December 2019

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by Zhenyu Pan, The First Hospital of Jilin University:
Leptomeningeal metastasis
Malignant solid tumors
Pemetrexed
Intrathecal chemotherapy
Radiotherapy
Additional relevant MeSH terms:
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Neoplasm Metastasis
Neoplasms, Second Primary
Meningeal Carcinomatosis
Neoplastic Processes
Neoplasms
Pathologic Processes
Meningeal Neoplasms
Central Nervous System Neoplasms
Nervous System Neoplasms
Neoplasms by Site
Nervous System Diseases
Dexamethasone
Pemetrexed
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Folic Acid Antagonists
Nucleic Acid Synthesis Inhibitors