Overview

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

Status:
Active, not recruiting
Trial end date:
2022-12-31
Target enrollment:
0
Participant gender:
All
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.
Phase:
Phase 1/Phase 2
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
OHSU Knight Cancer Institute
Collaborators:
National Cancer Institute (NCI)
National Institute of Neurological Disorders and Stroke (NINDS)
Oregon Health and Science University
Treatments:
Antidotes
Carboplatin
Mannitol
Mechlorethamine
Melphalan
Nitrogen Mustard Compounds
Sodium thiosulfate
Criteria
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)

- Subjects or their legal guardian must sign a written informed consent in accordance
with institutional guidelines

- Sexually active women of child-bearing potential and men must agree to use adequate
contraception (hormonal or barrier method of birth control; abstinence) prior to study
treatment and for the duration of study treatment; should a female become pregnant or
suspect she is pregnant while participating in this study, she should inform her
treating physician immediately

- For the phase II portion of the study, subjects must have disease that is evaluable
for response; subjects who have had radiation to all sites of disease are not eligible
unless there is imaging evidence of active tumor, ie: increased blood volume

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