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

NCT00983398 | Unknown Phase 1 DMC FDA Drug

• 6 other identifiers: IRB00005056NCI-2013-00790OHSU-5056MR000425515056R01NS044687
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 2

Brief 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.

Conditions

Central Nervous System Embryonal Neoplasm; Embryonal Tumor With Multilayered Rosettes, C19MC-Altered; Germ Cell Tumor; Medulloblastoma; Medulloepithelioma; Primitive Neuroectodermal Tumor; Recurrent Childhood Central Nervous System Embryonal Neoplasm; Recurrent Malignant Germ Cell Tumor; Recurrent Medulloblastoma; Recurrent Primitive Neuroectodermal Tumor

Outcome Measures

Primary Outcomes (2)

• Maximum tolerated dose (Phase I)

  Will be assessed based on the incidence of dose-limiting toxicity, graded using the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0. All toxicities will be tabulated by event and by overall. The toxicities will also be tabulated by highest grade. The recovery from toxicities (i.e. hematologic toxicities) will also be summarized.

  6 weeks

• Response rate (Phase II)

  Descriptive statistics will be estimated.

  Up to 5 years

Secondary Outcomes (4)

• Progression free survival rate (Phase II)

  Time from first study treatment to evidence of first progression, assessed at 2 years

• Overall survival rate (Phase II)

  Time from time of first study treatment until death, assessed at 2 years

• Change in neurocognitive assessment scores (Phase II)

  Baseline to 90 days after completion of study treatment

• Proportion of patients with ototoxicity (Phase II)

  Up to 30 days after completion of study treatment

Study Arms (1)

Treatment (mannitol, melphalan, carboplatin, STS)

EXPERIMENTAL

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.

Drug: Carboplatin; Drug: Mannitol; Drug: Melphalan; Other: Quality-of-Life Assessment; Other: Questionnaire Administration; Drug: Sodium Thiosulfate

Interventions

Carboplatin DRUG

Given IA

Also known as: Blastocarb, Carboplat, Carboplatin Hexal, Carboplatino, Carboplatinum, Carbosin, Carbosol, Carbotec, CBDCA, Displata, Ercar, JM-8, Nealorin, Novoplatinum, Paraplatin, Paraplatin AQ, Paraplatine, Platinwas, Ribocarbo

Treatment (mannitol, melphalan, carboplatin, STS)

Mannitol DRUG

Given IA

Also known as: D-Mannitol, Mannitol, D-, Osmitrol, Resectisol

Treatment (mannitol, melphalan, carboplatin, STS)

Melphalan DRUG

Given IA

Also known as: Alanine Nitrogen Mustard, CB-3025, L-PAM, L-Phenylalanine Mustard, L-Sarcolysin, L-Sarcolysin Phenylalanine mustard, L-Sarcolysine, Melphalanum, Phenylalanine Mustard, Phenylalanine Nitrogen Mustard, Sarcoclorin, Sarkolysin, WR-19813

Treatment (mannitol, melphalan, carboplatin, STS)

Quality-of-Life Assessment OTHER

Ancillary studies

Also known as: Quality of Life Assessment

Treatment (mannitol, melphalan, carboplatin, STS)

Questionnaire Administration OTHER

Ancillary studies

Treatment (mannitol, melphalan, carboplatin, STS)

Sodium Thiosulfate DRUG

Given IV

Also known as: Cyanide Antidote Package, Disodium Thiosulfate, S-Hydril, Sodium Hyposulfate, Sodium Thiosulfate Pentahydrate, Sodium Thiosulphate, Sodothiol, Thiosulfate, Sodium, Pentahydrate, Thiosulfuric Acid Disodium Salt

Treatment (mannitol, melphalan, carboplatin, STS)

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• OHSU Knight Cancer Institute: lead
• National Institute of Neurological Disorders and Stroke (NINDS): collaborator
• Oregon Health and Science University: collaborator

Study Sites (2)

University of Minnesota/Masonic Cancer Center

Minneapolis, Minnesota, 55455, United States

Location

OHSU Knight Cancer Institute

Portland, Oregon, 97239, United States

Location

MeSH Terms

Conditions

Neuroectodermal Tumors, Primitive; Neoplasms, Germ Cell and Embryonal; Medulloblastoma

Interventions

Carboplatin; Mannitol; Melphalan; sodium thiosulfate

Condition Hierarchy (Ancestors)

Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Glioma

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Sugar Alcohols; Alcohols; Carbohydrates; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins

Study Officials

• Edward A Neuwelt

  OHSU Knight Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: September 23, 2009
• First Posted: September 24, 2009
• Study Start: July 9, 2009
• Primary Completion: December 31, 2021
• Study Completion: December 31, 2022
• Last Updated: October 26, 2021

Record last verified: 2021-10

Locations

US (2)