Intra-pemetrexed Alone or Combined With Concurrent Radiotherapy for Leptomeningeal Metastasis

NCT05305885 | Unknown DMC

• 1 other identifier: PMRT
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

Intrathecal chemotherapy is one of the mainstay treatment options for leptomeningeal metastases. Owing to the limited number of agents available for intrathecal chemotherapy, it is crucial to find a novel agent with efficacy and safety. In our phase 1 study, intrathecal pemetrexed showed controllable toxicities and potential promising efficacy for refractory leptomeningeal metastases from non-small-cell lung cancer patients. In our further study, intrathecal pemetrexed combined with involved-field radiation therapy was administered as the first-line intrathecal chemotherapy for leptomeningeal metastases from solid tumors. In this study, intrathecal pemetrexed combined with involved-field radiation therapy showed feasibility and controllable adverse events. It has been proved that pemetrexed as a novel intrathecal drug exhibited promising antitumor effects in cerebrospinal fluid. Moreover, the concomitant therapeutic modality is an optimal treatment option for leptomeningeal metastases from solid tumors. Central nervous system radiotherapy is a part of the specific treatment of leptomeningeal metastases. Radiotherapy has been proved to improve neurologic function and control of parenchymal brain metastases in leptomeningeal metastases treatment. Additionally, radiotherapy is revealed to improve the efficacy and attenuate toxicity of intrathecal chemotherapy as a result of normal cerebrospinal fluid reestablishing. However, it is still controversial whether radiotherapy can improve the overall survival. We conduct this study to further demonstrate the efficacy and safety of intrathecal pemetrexed administration for patients with leptomeningeal metastases from solid tumors by multicenter study. Furthermore, the study of effective treatment modality is of great significance. The safety and antitumor activity of intrathecal pemetrexed combined with involved-field radiation therapy and intrathecal pemetrexed alone were also compared to confirm an optimized therapeutic regimen.

Conditions

Leptomeningeal Metastasis

Keywords

Leptomeningeal metastasis; Malignant solid tumors; Pemetrexed; Intrathecal chemotherapy; Radiotherapy

Outcome Measures

Primary Outcomes (2)

• Clinical response rate

  The response assessment in neuro-oncology criteria (RANO) proposal for response criteria of leptomeningeal metastasis was used to assess the clinical response in this study.

  From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 6 months.

• Incidence of treatment-related adverse events

  The incidence of treatment-related adverse events were measured for determining 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.

  From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 6 months.

Secondary Outcomes (2)

• Overall survival

  From the enrollment of this study until date of death from any cause, whichever came first, or the last follow-up (at least 7 months).

• Neurological progression-free survival (NPFS)

  From date of randomization until the date of first documented neurological progression or date of death from any cause, whichever came first, assessed up to 6 months.

Study Arms (2)

Group 1

EXPERIMENTAL

Intrathecal administration, intraventricular administration or via lumbar puncture, pemetrexed plus dexamethasone, first induction intra-cerebrospinal fluid chemotherapy twice per week for 2 weeks, then once per week for 4 times, 6 weeks in total. Concurrent 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 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 Gy.

Drug: Pemetrexed; Radiation: Radiotherapy

Group 2

EXPERIMENTAL

Intrathecal administration, intraventricular administration or via lumbar puncture, pemetrexed plus dexamethasone, first induction intra-cerebrospinal fluid chemotherapy twice per week for 2 weeks, then once per week for 4 times, 6 weeks in total.

Drug: Pemetrexed

Interventions

Pemetrexed DRUG

Intrathecal administration, intraventricular administration or via lumbar puncture, pemetrexed plus dexamethasone, first induction intra-cerebrospinal fluid chemotherapy twice per week for 2 weeks, then once per week for 4 times, 6 weeks in total.

Group 1; Group 2

Radiotherapy RADIATION

Concurrent 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 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 Gy.

Group 1

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 with a confirmed or probable diagnosis of leptomeningeal metastasis according to European Association of Neuro-Oncology-European Society for Medical Oncology (EANO-ESMO) guidelines；Patients who have been definitely diagnosed as leptomeningeal metastasis according to cerebrospinal fluid cytology, or patients who got the clinical diagnosis by combining with neuroimaging, history of cancer, clinical manifestation, cerebrospinal fluid examination, etc.
• Participants with histologically or cytologically confirmed disease from solid tumors;
• No history of whole brain radiotherapy;
• Normal liver and kidney function; WBC≥4000/mm3, Plt≥100000/mm3.

You may not qualify if:

• Patients with primary tumor of hematological tumors or primary central germ cell tumors;
• Patients administrated with new molecular targeted therapy which is effective for leptomeningeal metastasis in 2 weeks;
• Patients with hydrocephalus or other factors suggestive of cerebrospinal fluid circulation obstruction;
• Patients with severe encephalopathy, grade 3 leukoencephalopathy, Glasgow Coma Scale less than 8 score;
• Patients with extensive and lethal systemic diseases with few treatment options;
• 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
• The Second Hospital of Hebei Medical University: collaborator
• Second Affiliated Hospital of Guangzhou Medical University: collaborator
• Affiliated Hospital of Guangdong Medical University: collaborator
• Guangdong 999 Brain Hospital: collaborator
• Wuxi People's Hospital: collaborator
• Huizhou Third People's Hospital, Guangzhou Medical University: collaborator
• Panjin Liaoyou Gem Flower Hospital: collaborator

Study Sites (1)

The First Hospital of Jilin University

Changchun, Jilin, 130021, China

RECRUITING

Related Publications (3)

• Pan Z, Yang G, He H, Cui J, Li W, Yuan T, Chen K, Jiang T, Gao P, Sun Y, Cong X, Li Z, Wang Y, Pang X, Song Y, Zhao G. Intrathecal pemetrexed combined with involved-field radiotherapy as a first-line intra-CSF therapy for leptomeningeal metastases from solid tumors: a phase I/II study. Ther Adv Med Oncol. 2020 Jul 17;12:1758835920937953. doi: 10.1177/1758835920937953. eCollection 2020.

  PMID: 32733606 BACKGROUND

• Pan Z, Yang G, He H, Gao P, Jiang T, Chen Y, Zhao G. Identification of Cerebrospinal Fluid MicroRNAs Associated With Leptomeningeal Metastasis From Lung Adenocarcinoma. Front Oncol. 2020 Apr 3;10:387. doi: 10.3389/fonc.2020.00387. eCollection 2020.

  PMID: 32328453 BACKGROUND

• Pan Z, Yang G, Cui J, Li W, Li Y, Gao P, Jiang T, Sun Y, Dong L, Song Y, Zhao G. A Pilot Phase 1 Study of Intrathecal Pemetrexed for Refractory Leptomeningeal Metastases From Non-small-cell Lung Cancer. Front Oncol. 2019 Aug 30;9:838. doi: 10.3389/fonc.2019.00838. eCollection 2019.

  PMID: 31544065 BACKGROUND

MeSH Terms

Conditions

Meningeal Carcinomatosis

Interventions

Pemetrexed; Radiotherapy

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Dicarboxylic; Therapeutics

Study Officials

• Zhenyu Pan, PhD.

  The First Hospital of Jilin University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Zhenyu Pan, PhD.

CONTACT

+8615804302753; dr-zypan@163.com

Guozi Yang, PhD.

CONTACT

+8615804302755; guoziyang_1982@163.com

Study Design

• Study Type: interventional
• Phase: not applicable
• 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 14, 2022
• First Posted: March 31, 2022
• Study Start: August 19, 2022
• Primary Completion: October 1, 2023
• Study Completion: July 1, 2024
• Last Updated: September 30, 2022

Record last verified: 2022-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• Time Frame: Starting 6 months after publication.
• Access Criteria: Individual participant data will be public accessable via contacting with principal investigator by email within 6 months after the trial complete.

Locations

CN (1)