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

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: Phase I/II Study of Carboplatin, Melphalan and Etoposide Phosphate in Conjunction With Osmotic Opening of the Blood-Brain Barrier and Delayed Intravenous Sodium Thiosulfate Chemoprotection, in Previou

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. 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 Summary:

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 e
Sponsor: OHSU Knight Cancer Institute

Current Primary Outcome:

  • 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) [ Time Frame: 4 weeks ]
  • Overall survival [ Time Frame: 1 year ]
  • Progression free survival (Phase II) [ Time Frame: 1 year ]
    Kaplan-Meier method will be used. 95% confidence intervals estimated. Cox proportional hazards regression models will be fit to explore potential predictors.
  • Response rate [ Time Frame: 1 year ]
  • Time to best response [ Time Frame: 1 year ]


Original Primary Outcome:

Current Secondary Outcome:

  • Functional outcomes [ Time Frame: 1 year ]
    Descriptive numeric and graphical summaries for functional status, quality of life, and cognitive function will be estimated for all subjects and separately for subjects with anaplastic oligodendrogliomas and oligoastrocytomas.
  • Incidence of severe neutropenia (specifically febrile neutropenia or sepsis) in accordance with NCI CTC (version 3.0) [ Time Frame: 1 year ]
    Incidence rates of grade III/IV events and associated 95% confidence intervals will be estimated.
  • Rates of 2YPFS for specific tumor types [ Time Frame: 2 years ]
    Separate estimates of 2YPFS and overall survival (and associated confidence intervals) will be made for subjects with anaplastic oligodendroglioma and for subjects with oligoastrocytoma. Confidence intervals will also be used to describe differences between this subject series and our earlier subject series.


Original Secondary Outcome:

Information By: OHSU Knight Cancer Institute

Dates:
Date Received: March 15, 2006
Date Started: September 2005
Date Completion: December 2019
Last Updated: April 19, 2017
Last Verified: April 2017