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

NCT ID: NCT03507244

Last Updated: 2019-12-26

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1/PHASE2

Total Enrollment

34 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-04-12

Study Completion Date

2019-07-30

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Leptomeningeal Metastasis

Keywords

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Leptomeningeal metastasis Malignant solid tumors Pemetrexed Intrathecal chemotherapy Radiotherapy

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

Pemetrexed

Intervention Type DRUG

Pemetrexed, 10 mg,intrathecal injection, plus dexamethasone 5 mg, once per week, 5 to 8 times, 4 to 7 weeks in total.

Dexamethasone

Intervention Type DRUG

Dexamethasone, 5 mg, intrathecal injection, simultaneously with pemetrexed, once per week, 5 to 8 times, 4 to 7 weeks in total.

Radiotherapy

Intervention Type RADIATION

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.

Interventions

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Pemetrexed

Pemetrexed, 10 mg,intrathecal injection, plus dexamethasone 5 mg, once per week, 5 to 8 times, 4 to 7 weeks in total.

Intervention Type DRUG

Dexamethasone

Dexamethasone, 5 mg, intrathecal injection, simultaneously with pemetrexed, once per week, 5 to 8 times, 4 to 7 weeks in total.

Intervention Type DRUG

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.

Intervention Type RADIATION

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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The First Hospital of Jilin University

OTHER

Sponsor Role lead

Responsible Party

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Zhenyu Pan

Professor

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Zhenyu Pan, Professor

Role: PRINCIPAL_INVESTIGATOR

The First Hospital of Jilin University

Locations

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The First Hospital of Jilin University

Changchun, Jilin, China

Site Status

Countries

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China

References

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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.

Reference Type RESULT
PMID: 27243238 (View on PubMed)

Stoop MP, Visser S, van Dijk E, Aerts JGJV, Stricker BH, Luider TM. A new quantification method for assessing plasma concentrations of pemetrexed and its polyglutamate metabolites. J Pharm Biomed Anal. 2016 Sep 5;128:1-8. doi: 10.1016/j.jpba.2016.04.036. Epub 2016 Apr 30.

Reference Type RESULT
PMID: 27209449 (View on PubMed)

Chattopadhyay S, Moran RG, Goldman ID. Pemetrexed: biochemical and cellular pharmacology, mechanisms, and clinical applications. Mol Cancer Ther. 2007 Feb;6(2):404-17. doi: 10.1158/1535-7163.MCT-06-0343.

Reference Type RESULT
PMID: 17308042 (View on PubMed)

Sorensen JB. Pharmacokinetic evaluation of pemetrexed. Expert Opin Drug Metab Toxicol. 2011 Jul;7(7):919-28. doi: 10.1517/17425255.2011.587411. Epub 2011 May 21.

Reference Type RESULT
PMID: 21599552 (View on PubMed)

Adjei AA. Pharmacology and mechanism of action of pemetrexed. Clin Lung Cancer. 2004 Apr;5 Suppl 2:S51-5. doi: 10.3816/clc.2004.s.003.

Reference Type RESULT
PMID: 15117425 (View on PubMed)

Mita AC, Sweeney CJ, Baker SD, Goetz A, Hammond LA, Patnaik A, Tolcher AW, Villalona-Calero M, Sandler A, Chaudhuri T, Molpus K, Latz JE, Simms L, Chaudhary AK, Johnson RD, Rowinsky EK, Takimoto CH. Phase I and pharmacokinetic study of pemetrexed administered every 3 weeks to advanced cancer patients with normal and impaired renal function. J Clin Oncol. 2006 Feb 1;24(4):552-62. doi: 10.1200/JCO.2004.00.9720. Epub 2006 Jan 3.

Reference Type RESULT
PMID: 16391300 (View on PubMed)

McDonald AC, Vasey PA, Adams L, Walling J, Woodworth JR, Abrahams T, McCarthy S, Bailey NP, Siddiqui N, Lind MJ, Calvert AH, Twelves CJ, Cassidy J, Kaye SB. A phase I and pharmacokinetic study of LY231514, the multitargeted antifolate. Clin Cancer Res. 1998 Mar;4(3):605-10.

Reference Type RESULT
PMID: 9533527 (View on PubMed)

Rinaldi DA, Kuhn JG, Burris HA, Dorr FA, Rodriguez G, Eckhardt SG, Jones S, Woodworth JR, Baker S, Langley C, Mascorro D, Abrahams T, Von Hoff DD. A phase I evaluation of multitargeted antifolate (MTA, LY231514), administered every 21 days, utilizing the modified continual reassessment method for dose escalation. Cancer Chemother Pharmacol. 1999;44(5):372-80. doi: 10.1007/s002800050992.

Reference Type RESULT
PMID: 10501910 (View on PubMed)

Stapleton SL, Reid JM, Thompson PA, Ames MM, McGovern RM, McGuffey L, Nuchtern J, Dauser R, Blaney SM. Plasma and cerebrospinal fluid pharmacokinetics of pemetrexed after intravenous administration in non-human primates. Cancer Chemother Pharmacol. 2007 Mar;59(4):461-6. doi: 10.1007/s00280-006-0285-7. Epub 2006 Jul 20.

Reference Type RESULT
PMID: 16855840 (View on PubMed)

Kumthekar P, Grimm SA, Avram MJ, Kaklamani V, Helenowski I, Rademaker A, Cianfrocca M, Gradishar W, Patel J, Mulcahy M, McCarthy K, Raizer JJ. Pharmacokinetics and efficacy of pemetrexed in patients with brain or leptomeningeal metastases. J Neurooncol. 2013 Apr;112(2):247-55. doi: 10.1007/s11060-013-1055-0. Epub 2013 Jan 25.

Reference Type RESULT
PMID: 23354655 (View on PubMed)

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.

Reference Type DERIVED
PMID: 32733606 (View on PubMed)

Other Identifiers

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IPLM

Identifier Type: -

Identifier Source: org_study_id