Carboplatin, Melphalan, Etoposide Phosphate, Mannitol, and Sodium Thiosulfate in Treating Patients With Previously Treated Brain Tumors

NCT00303849 | Completed Phase 1 DMC

• 4 other identifiers: IRB00002868NCI-2013-00786CR000024562868
• Study Type: interventional
• Target: 33
• 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, etoposide phosphate, mannitol, and sodium thiosulfate and to see how well they work in treating patients with previously treated brain tumors. Drugs used in chemotherapy, such as melphalan, carboplatin, and etoposide phosphate, work in different ways to stop the growth of tumor cells, either by killing the cells or 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 carboplatin, melphalan, etoposide phosphate, mannitol, and sodium thiosulfate together may be an effective treatment for brain tumors.

Conditions

Anaplastic Oligoastrocytoma; Anaplastic Oligodendroglioma; Mixed Glioma; Oligoastrocytoma

Outcome Measures

Primary Outcomes (5)

• MTD of melphalan, defined as one dose level below the dose that produces grade 4 toxicity in 33% of patients, graded in accordance with National Cancer Institute Common Toxicity Criteria (NCI CTC) (version 3.0) (Phase I)

  4 weeks

• Overall survival

  1 year

• Progression free survival (Phase II)

  Kaplan-Meier method will be used. 95% confidence intervals estimated. Cox proportional hazards regression models will be fit to explore potential predictors.

  1 year

• Response rate

  1 year

• Time to best response

  1 year

Secondary Outcomes (3)

• Functional outcomes

  1 year

• Incidence of severe neutropenia (specifically febrile neutropenia or sepsis) in accordance with NCI CTC (version 3.0)

  1 year

• Rates of two year progression free survival (2YPFS) for specific tumor types

  2 years

Study Arms (1)

Treatment (etoposide, mannitol, melphalan, carboplatin, STS)

EXPERIMENTAL

Patients receive etoposide phosphate IV over 10 minutes, mannitol IA over 30 seconds, melphalan IA over 10 minutes, and carboplatin IA over 10 minutes on days 1 and 2. Patients then receive sodium thiosulfate IV over 15 minutes at 4 and 8 hours after carboplatin. Courses repeat every 4 to 6 weeks for up to 12 months.

Drug: Carboplatin; Drug: Etoposide; Drug: Etoposide Phosphate; Other: Laboratory Biomarker Analysis; Drug: Mannitol; Drug: Melphalan; Other: Quality-of-Life Assessment; 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 (etoposide, mannitol, melphalan, carboplatin, STS)

Etoposide DRUG

Given IV

Also known as: Demethyl Epipodophyllotoxin Ethylidine Glucoside, EPEG, Lastet, Toposar, Vepesid, VP 16, VP 16-213, VP-16, VP-16-213, VP16

Treatment (etoposide, mannitol, melphalan, carboplatin, STS)

Etoposide Phosphate DRUG

Given IV

Also known as: Etopophos

Treatment (etoposide, mannitol, melphalan, carboplatin, STS)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (etoposide, mannitol, melphalan, carboplatin, STS)

Mannitol DRUG

Given IA

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

Treatment (etoposide, 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 (etoposide, mannitol, melphalan, carboplatin, STS)

Quality-of-Life Assessment OTHER

Ancillary studies

Also known as: Quality of Life Assessment

Treatment (etoposide, 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 (etoposide, mannitol, melphalan, carboplatin, STS)

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects with pathologic evidence of an anaplastic oligodendroglioma or mixed glioma (i.e. oligoastrocytoma) are eligible; histopathologic diagnosis will be made using World Health Organization classification criteria; to qualify as a mixed tumor there must be a minimum of 25% oligodendroglial element
• Surgical procedure may have been complete resection, partial resection, or biopsy
• Subjects must have had prior treatment with temozolomide; at least 28 days must have elapsed since completion of temozolomide or other chemotherapy
• If subject has not undergone radiation therapy, then subject must have undergone prior consultation with a radiation oncologist (who is not an investigator on this study); if the subject has undergone radiation therapy, then at least 14 days must have elapsed since completion of radiation
• Subjects performance status must be (Karnofsky performance status \[KPS\] greater than or equal to 50; Eastern Cooperative Oncology Group \[ECOG\] less than or equal to 2)
• White blood cell count \>= 2.5 x 10\^3/mm\^3
• Absolute granulocyte count \> 1.5 x 10\^3/mm\^3
• Platelets \>= 100 x 10\^3/mm\^3
• Serum creatinine \< 1.5 x upper limit of normal
• Bilirubin \< 1.5 x upper limit of normal
• Subjects baseline serum glutamic oxaloacetic transaminase (SGOT)/serum glutamate pyruvate transaminase (SGPT) must be \< 2.5 x institutional upper limit of normal
• Subjects must sign a written informed consent in accordance with institutional guidelines
• The effects of carboplatin, melphalan and etoposide phosphate on the developing human fetus at the recommended therapeutic dose are unknown. For this reason and because these agents as well as other therapeutic agents used in this trial are known to be teratogenic. 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 woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately

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 for general anesthesia
• Subjects with uncontrolled (over the last 30 days) clinically significant confounding medical conditions
• Subject is pregnant, has a positive serum human chorionic gonadotropin (hCG) or is lactating
• Subjects who have contraindications to carboplatin, melphalan, etoposide phosphate, or sodium thiosulfate

Sponsors & Collaborators

• OHSU Knight Cancer Institute: lead
• 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

Oligodendroglioma; Glioma; Astrocytoma

Interventions

Carboplatin; Etoposide; etoposide phosphate; Mannitol; Melphalan; sodium thiosulfate

Condition Hierarchy (Ancestors)

Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds; Glucosides; Glycosides; Carbohydrates; Sugar Alcohols; Alcohols; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; 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: Professor

Study Record Dates

• First Submitted: March 15, 2006
• First Posted: March 17, 2006
• Study Start: September 15, 2005
• Primary Completion: March 12, 2021
• Study Completion: March 12, 2021
• Last Updated: March 17, 2022

Record last verified: 2022-03

Locations

US (2)