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Melphalan, Carboplatin, Mannitol, and Sodium Thiosulfate in Treating Patients With Recurrent or Progressive CNS Embryonal or Germ Cell Tumors | Clinical Trials | Clareo Health

UNKNOWNPHASE1/PHASE2

Melphalan, Carboplatin, Mannitol, and Sodium Thiosulfate in Treating Patients With Recurrent or Progressive CNS Embryonal or Germ Cell Tumors

Phase I/II Study of Intra-Arterial Melphalan Given With Intra-Arterial Carboplatin, Osmotic Blood-Brain Barrier Disruption and Delayed Otoprotective Sodium Thiosulfate for Patients With Recurrent or Progressive CNS Embryonal or Germ Cell Tumors

NCT00983398•OHSU Knight Cancer Institute

View on ClinicalTrials.gov

Summary

This phase I/II trial studies the side effects and best dose of melphalan when given together with carboplatin, mannitol, and sodium thiosulfate, and to see how well they work in treating patients with central nervous system (CNS) embryonal or germ cell tumors that is growing, spreading, or getting worse (progressive) or has come back (recurrent). Drugs used in chemotherapy, such as melphalan and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Osmotic blood-brain barrier disruption (BBBD) uses mannitol to open the blood vessels around the brain and allow cancer-killing substances to be carried directly to the brain. Sodium thiosulfate may help lessen or prevent hearing loss and toxicities in patients undergoing chemotherapy with carboplatin and BBBD. Giving melphalan together with carboplatin, mannitol, and sodium thiosulfate may be an effective treatment for recurrent or progressive CNS embryonal or germ cell tumors.

Detailed Description

PRIMARY OBJECTIVES: I. To determine the maximum tolerated dose (MTD) of intra-arterial (IA) melphalan given with IA carboplatin, osmotic BBBD and delayed intravenous (IV) sodium thiosulfate (STS) in subjects with recurrent or progressive embryonal and germ cell tumors of the CNS. (Phase I) II. To estimate the response rate in subjects with recurrent or progressive CNS embryonal and germ cell tumors treated with IA carboplatin, IA melphalan, osmotic BBBD and delayed IV STS. (Phase II) SECONDARY OBJECTIVES: I. To describe 2-year progression-free survival (PFS) and overall survival (OS) rates in subjects with recurrent or progressive CNS embryonal and germ cell tumors treated with IA carboplatin, IA melphalan, osmotic BBBD and delayed IV STS. (Phase II) II. To describe neuropsychological and audiology outcomes in subjects with recurrent or progressive CNS embryonal and germ cell tumors treated with IA carboplatin, IA melphalan, osmotic BBBD and delayed IV STS. (Phase II) III. To describe the overall toxicity of IA carboplatin and IA melphalan in conjunction with osmotic BBBD and delayed STS chemoprotection in subjects with recurrent or progressive CNS embryonal or germ cell tumors. (Phase II) OUTLINE: This is a phase I, dose-escalation study of melphalan followed by a phase II study. Patients receive mannitol IA over 30 seconds, melphalan IA over 10 minutes, and carboplatin IA over 10 minutes. Patients then receive sodium thiosulfate IV over 15 minutes at 4 and 8 hours after carboplatin. Treatment repeats every 4-6 weeks for up to 12 cycles in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 3 months for 1 year, every 6 months for 1 year, and then annually for 3 years.

Eligibility

Age

18 - 45 years

Sex

ALL

Healthy Volunteers

Inclusion Criteria

•Subjects with histologically confirmed CNS embryonal tumor (primitive neuroectodermal tumor \[PNET\], medulloblastoma, atypical teratoid rhabdoid tumor \[ATRT\], medulloepithelioma, pineoblastoma or ependymoblastoma), or germ cell tumor, are eligible; subjects may be enrolled on study as first-line treatment; diagnosis will be made on the basis of computed tomography (CT)-assisted or stereotactic biopsy, open biopsy, surgical resection, cerebrospinal fluid (CSF) cytology, or elevated tumor markers
•Subjects may be enrolled as part of first-line treatment; those subjects who enroll as first-line treatment will not be restricted from traditional treatments in the future; at least 14 days must have elapsed since completion of cranial radiotherapy and 28 days since completion of chemotherapy; at least 28 days must have elapsed since completion of total spine radiotherapy
•Subjects with no previous radiotherapy treatment must have a consultation with a radiation oncologist or providers must have a discussion in the context of Neuro-Oncology Tumor Board within 60 days prior to start of IA/BBBD chemotherapy to determine the need for radiotherapy prior to or after IA/BBBD
•Glomerular filtration rate (GFR) or creatinine clearance (CrCl) (24 hour urine) greater than 30 ml/min corrected for body surface area
•Absolute granulocyte count \>= 1.0 x 10\^3/mm\^3
•Platelets \>= 100 x 10\^3/mm\^3
•Creatinine \< 1.5
•Total bilirubin \< 2.0 mg/dl
•Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) \< 2.5 x upper limits of normal
•Subject's Karnofsky performance status (KPS) must be \>= 50% (Eastern Cooperative Oncology Group \[ECOG\] performance score \< 3)
+2 more criteria

Exclusion Criteria

•Subjects with radiographic signs of excessive intracranial mass effect with associated rapid neurologic deterioration and/or spinal cord block
•Subjects at significant risk with general anesthesia
•Subjects with uncontrolled (over the last 30 days) clinically significant confounding medical conditions
•Subject is pregnant or is lactating
•Subjects who have contraindications to carboplatin, melphalan, or STS

Locations (2)

University of Minnesota/Masonic Cancer Center

Minneapolis, Minnesota, United States

OHSU Knight Cancer Institute

Portland, Oregon, United States

Key Dates

Start Date

July 9, 2009

Primary Completion Date

December 31, 2021

Completion Date

December 31, 2022

Last Updated

October 26, 2021

Enrollment

ACTUAL participants

Conditions

Central Nervous System Embryonal NeoplasmEmbryonal Tumor With Multilayered Rosettes, C19MC-AlteredGerm Cell TumorMedulloblastomaMedulloepitheliomaPrimitive Neuroectodermal TumorRecurrent Childhood Central Nervous System Embryonal NeoplasmRecurrent Malignant Germ Cell TumorRecurrent MedulloblastomaRecurrent Primitive Neuroectodermal Tumor

Interventions

Carboplatin

DRUG

Mannitol

DRUG

Melphalan

DRUG

Quality-of-Life Assessment

OTHER

Questionnaire Administration

OTHER

Sodium Thiosulfate

DRUG

Active Surveillance, Bleomycin, Etoposide, Carboplatin or Cisplatin in Treating Pediatric and Adult Patients With Germ Cell Tumors

NCT03067181

Childhood Extracranial Germ Cell TumorExtragonadal Embryonal Carcinoma+28 more

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Testing the Addition of Pedmark to Cisplatin Chemotherapy for Reducing Drug-Induced Ear Damage in Men With Stage II-III Metastatic Testicular Germ Cell Tumors

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Hearing LossMetastatic Malignant Germ Cell Tumor+5 more

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Data Source & Attribution

This clinical trial information is sourced from ClinicalTrials.gov, a service of the U.S. National Institutes of Health.

ClinicalTrials.gov last update: October 26, 2021Data synced to Clareo: March 29, 2026

Modifications: This data has been reformatted for display purposes. Eligibility criteria have been parsed into inclusion/exclusion sections. Location data has been geocoded to enable distance-based search. For the authoritative and most current information, please visit ClinicalTrials.gov.

Neither the United States Government nor Clareo Health make any warranties regarding the data. Check ClinicalTrials.gov frequently for updates.

View ClinicalTrials.gov Terms and Conditions

Melphalan, Carboplatin, Mannitol, and Sodium Thiosulfate in Treating Patients With Recurrent or Progressive CNS Embryonal or Germ Cell Tumors

Inclusion Criteria

Exclusion Criteria

Active Surveillance, Bleomycin, Etoposide, Carboplatin or Cisplatin in Treating Pediatric and Adult Patients With Germ Cell Tumors

Testing the Addition of Pedmark to Cisplatin Chemotherapy for Reducing Drug-Induced Ear Damage in Men With Stage II-III Metastatic Testicular Germ Cell Tumors

Observational Study for Assessing Treatment and Outcome of Patients With Primary Brain Tumours Using cIMPACT-NOW and 2021 WHO Classification

Maintenance Zanzalintinib With Etoposide After HDCT in GCT

Molecular Epidemiology of Pediatric Germ Cell Tumors

Treatment of Newly Diagnosed Central Malignant Germ Cell Tumor People With Teniposide Injection Combined With Cisplatin.