Carboplatin, Melphalan, Etoposide Phosphate, Mannitol, and Sodium Thiosulfate in Treating Patients With Previously Treated Brain Tumors
Condition: Anaplastic Oligoastrocytoma; Anaplastic Oligodendroglioma; Mixed Glioma; Oligoastrocytoma
MeSH terms: Oligodendroglioma; Glioma
Study type: Interventional
Phase: Phase 1/Phase 2

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.
    

Detailed description: 
      PRIMARY OBJECTIVES:

      I. To evaluate toxicity and estimate the maximum tolerated dose (MTD) of melphalan
      (intra-arterially [i.a.]) administered in conjunction with carboplatin (i.a.) and etoposide
      phosphate (intravenously [i.v.]) undergoing BBBD, in subjects with anaplastic
      oligodendroglioma or oligoastrocytoma. (Phase I) II. To examine the efficacy (one year
      progression free survival [1YPFS]) of carboplatin (i.a.), melphalan (i.a.) and etoposide
      phosphate (i.v.) in conjunction with BBBD, in subjects with anaplastic oligodendroglioma or
      oligoastrocytoma. (Phase II)

      SECONDARY OBJECTIVES:

      I. To evaluate the incidence of severe neutropenia (specifically febrile neutropenia or
      sepsis) of carboplatin (i.a.), melphalan (i.a.) and etoposide phosphate (i.v.) in conjunction
      with BBBD, in subjects with anaplastic oligodendroglioma or oligoastrocytoma.

      II. To evaluate the overall toxicity of carboplatin (i.a.), melphalan (i.a.), and etoposide
      phosphate (i.v.) in conjunction with BBBD.

      III. To estimate the differences in tumor response, 1YPFS and survival, in subjects with
      allelic loss of chromosomes 1p and 19q, and tumor protein p53 (p53) immunocytochemistry,
      versus subjects without allelic loss.

      IV. To assess quality of life, cognitive function, and performance status of subjects
      undergoing treatment with carboplatin, melphalan and etoposide phosphate in conjunction with
      BBBD.

      V. To estimate differences in 1YPFS between subjects with anaplastic oligodendroglioma and
      patients with oligoastrocytoma.

      VI. To describe the role of biopsy versus extent of surgery (sub-maximal versus maximal safe
      resection) on 1YPFS and survival.

      VII. To describe the role of prior radiation on tumor response, 1YPFS and survival.

      OUTLINE: This is a phase I, dose-escalation study of melphalan followed by a phase II study.

      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.

      After completion of study treatment, patients are followed up every 3 months for 1 year,
      every 6 months for 2 years, and then annually thereafter.
    

Intervention name(s): Carboplatin; Etoposide; Etoposide Phosphate; Laboratory Biomarker Analysis; Mannitol; Melphalan; Quality-of-Life Assessment; Sodium Thiosulfate
Intervention type(s): Drug; Drug; Drug; Other; Drug; Drug; Other; Drug
Intervention description(s): Given IA; Given IV; Given IV; Correlative studies; Given IA; Given IA; Ancillary studies; Given IV
Other intervention name(s): Blastocarb; Carboplat; Carboplatin Hexal; Carboplatino; Carboplatinum; Carbosin; Carbosol; Carbotec; CBDCA; Displata; Ercar; JM-8; Nealorin; Novoplatinum; Paraplatin; Paraplatin AQ; Paraplatine; Platinwas; Ribocarbo; Demethyl Epipodophyllotoxin Ethylidine Glucoside; EPEG; Lastet; Toposar; Vepesid; VP 16; VP 16-213; VP-16; VP-16-213; VP16; Etopophos; D-Mannitol; Mannitol, D-; Osmitrol; Resectisol; 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; Quality of Life Assessment; Cyanide Antidote Package; Disodium Thiosulfate; S-Hydril; Sodium Hyposulfate; Sodium Thiosulfate Pentahydrate; Sodium Thiosulphate; Sodothiol; Thiosulfate, Sodium, Pentahydrate; Thiosulfuric acid disodium salt
Intervention MeSH terms: Sodium thiosulfate; Carboplatin; Etoposide; Etoposide phosphate; Melphalan; Mechlorethamine; Podophyllotoxin; Nitrogen Mustard Compounds; Mannitol; Antidotes
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment