Now Available: Final Rule for FDAAA 801 and NIH Policy on Clinical Trial Reporting

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

This study is currently recruiting participants. (see Contacts and Locations)
Verified November 2016 by OHSU Knight Cancer Institute
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
OHSU Knight Cancer Institute
ClinicalTrials.gov Identifier:
NCT00303849
First received: March 15, 2006
Last updated: November 17, 2016
Last verified: November 2016
  Purpose
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.

Condition Intervention Phase
Adult Anaplastic Oligodendroglioma
Adult Mixed Glioma
Adult Oligodendroglioma
Oligoastrocytoma
Recurrent Adult Brain Neoplasm
Drug: Carboplatin
Drug: Etoposide Phosphate
Other: Laboratory Biomarker Analysis
Drug: Mannitol
Drug: Melphalan
Other: Quality-of-Life Assessment
Drug: Sodium Thiosulfate
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by OHSU Knight Cancer Institute:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]
  • Overall survival [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  • Progression free survival (Phase II) [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
  • Time to best response [ Time Frame: 1 year ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Functional outcomes [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: No ]
    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.


Estimated Enrollment: 43
Study Start Date: September 2005
Estimated Study Completion Date: December 2019
Estimated Primary Completion Date: December 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (etoposide, mannitol, melphalan, carboplatin, STS)
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
Given IA
Other Names:
  • Blastocarb
  • Carboplat
  • Carboplatin Hexal
  • Carboplatino
  • Carbosin
  • Carbosol
  • Carbotec
  • CBDCA
  • Displata
  • Ercar
  • JM-8
  • Nealorin
  • Novoplatinum
  • Paraplat
  • Paraplatin
  • Paraplatin AQ
  • Paraplatine
  • Platinwas
  • Ribocarbo
Drug: Etoposide Phosphate
Given IV
Other Name: Etopophos
Other: Laboratory Biomarker Analysis
Correlative studies
Drug: Mannitol
Given IA
Other Names:
  • D-Mannitol
  • Mannitol, D-
  • Osmitrol
  • Resectisol
Drug: Melphalan
Given IA
Other Names:
  • 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
Other: Quality-of-Life Assessment
Ancillary studies
Other Name: Quality of Life Assessment
Drug: Sodium Thiosulfate
Given IV
Other Names:
  • Cyanide Antidote Package
  • Disodium Thiosulfate
  • S-Hydril
  • Sodium Hyposulfate
  • Sodium Thiosulfate Pentahydrate
  • Sodium Thiosulphate
  • Sodothiol
  • Thiosulfate, Sodium, Pentahydrate
  • Thiosulfuric Acid Disodium Salt

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.

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00303849

Locations
United States, Minnesota
University of Minnesota/Masonic Cancer Center Recruiting
Minneapolis, Minnesota, United States, 55455
Contact: Matthew A. Hunt    612-624-1452    huntx188@umn.edu   
Principal Investigator: Matthew A. Hunt         
United States, Oregon
OHSU Knight Cancer Institute Recruiting
Portland, Oregon, United States, 97239
Contact: Edward A. Neuwelt    503-494-5626    trials@ohsu.edu   
Principal Investigator: Edward A. Neuwelt         
Sponsors and Collaborators
OHSU Knight Cancer Institute
National Cancer Institute (NCI)
Investigators
Principal Investigator: Edward Neuwelt OHSU Knight Cancer Institute
  More Information

Responsible Party: OHSU Knight Cancer Institute
ClinicalTrials.gov Identifier: NCT00303849     History of Changes
Other Study ID Numbers: IRB00002868  NCI-2013-00786  CR00002456  2868  IRB00002868  P30CA069533 
Study First Received: March 15, 2006
Last Updated: November 17, 2016
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Oligodendroglioma
Brain Neoplasms
Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Central Nervous System Neoplasms
Nervous System Neoplasms
Neoplasms by Site
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Etoposide phosphate
Carboplatin
Etoposide
Melphalan
Mechlorethamine
Nitrogen Mustard Compounds
Mannitol
Sodium thiosulfate
Antineoplastic Agents
Antineoplastic Agents, Phytogenic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on December 02, 2016