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