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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 : Recruiting
First Posted : April 25, 2018
Last Update Posted : November 21, 2018
Sponsor:
Information provided by (Responsible Party):
Zhenyu Pan, 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. In investigators' previous study, criteria of evaluation for clinical response has been established based on improvement of neurologic symptoms/signs and changes of Karnofsky Performance Status(KPS). The criteria were proved as effective method for the evaluation of prognosis. The method was used to assess the clinical response in this study.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
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
Estimated Primary Completion Date : May 31, 2019
Estimated Study Completion Date : December 31, 2019

Resource links provided by the National Library of Medicine


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 3.0). 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 clinical response rate will be determined based on the evaluation criteria which have been established and published on the previous paper by the investigators (Pan Z, et al. Int J Cancer. 2016;139:1864-72). This evaluation criteria were mainly based on two factors, including improvement of neurologic symptoms/signs and changes of Karnofsky Performance Status.

  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 leptomeningeal metastasis diagnosis. All patients were followed up until death or the end of the study.



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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


Contacts
Contact: Zhenyu Pan, Professor +8615804302753 dr-zypan@163.com
Contact: Guozi Yang, Professor +8615804302755 guoziyang_1982@163.com

Locations
China, Jilin
The First Hospital of Jilin University Recruiting
Changchun, Jilin, China, 130021
Contact: Zhenyu Pan, Professor    +8615804302753    dr-zypan@163.com   
Contact: Guozi Yang, Professor    +8615804302755    guoziyang_1982@163.com   
Sponsors and Collaborators
First Hospital of Jilin University
Investigators
Principal Investigator: Zhenyu Pan, Professor First Hospital of Jilin University

Publications of Results:

Responsible Party: Zhenyu Pan, Professor, First Hospital of Jilin University
ClinicalTrials.gov Identifier: NCT03507244     History of Changes
Other Study ID Numbers: IPLM
First Posted: April 25, 2018    Key Record Dates
Last Update Posted: November 21, 2018
Last Verified: November 2018

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, First Hospital of Jilin University:
Leptomeningeal metastasis
Malignant solid tumors
Pemetrexed
Intrathecal chemotherapy
Radiotherapy

Additional relevant MeSH terms:
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 acetate
Dexamethasone
Pemetrexed
BB 1101
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
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Folic Acid Antagonists