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

Information source: OHSU Knight Cancer Institute
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Adult Anaplastic Oligodendroglioma; Adult Mixed Glioma; Adult Oligodendroglioma; Recurrent Adult Brain Neoplasm

Intervention: Carboplatin (Drug); Etoposide Phosphate (Drug); Laboratory Biomarker Analysis (Other); Mannitol (Drug); Melphalan (Drug); Quality-of-Life Assessment (Other); Sodium Thiosulfate (Drug)

Phase: Phase 1/Phase 2

Status: Recruiting

Sponsored by: OHSU Knight Cancer Institute

Official(s) and/or principal investigator(s):
Edward Neuwelt, Principal Investigator, Affiliation: OHSU Knight Cancer Institute

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 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.

Clinical Details

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 Previously Treated Subjects With Anaplastic Oligodendroglioma or Oligoastrocytoma

Study design: Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

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)

Progression free survival (Phase II)

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

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 blood-brain barrier disruption (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 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.

Eligibility

Minimum age: 18 Years. Maximum age: 75 Years. Gender(s): Both.

Criteria:

Inclusion Criteria:

- 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/mm3

- 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

- 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 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 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

Locations and Contacts

University of Minnesota Medical Center-Fairview, Minneapolis, Minnesota 55455, United States; Recruiting
Matthew A. Hunt, Phone: 612-624-1452, Email: huntx188@umn.edu
Matthew A. Hunt, Principal Investigator

OHSU Knight Cancer Institute, Portland, Oregon 97239, United States; Recruiting
Edward A. Neuwelt, Phone: 503-494-5626, Email: trials@ohsu.edu
Edward A. Neuwelt, Principal Investigator

Additional Information

Starting date: September 2005
Last updated: August 7, 2015

Page last updated: August 23, 2015

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