- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00303849
Carboplatin, Melphalan, Etoposide Phosphate, Mannitol, and Sodium Thiosulfate in Treating Patients With Previously Treated Brain Tumors
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 Overview
Status
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.
Study Type
Enrollment (Actual)
Phase
- Phase 2
- Phase 1
Contacts and Locations
Study Locations
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Minnesota
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Minneapolis, Minnesota, United States, 55455
- University of Minnesota/Masonic Cancer Center
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Oregon
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Portland, Oregon, United States, 97239
- OHSU Knight Cancer Institute
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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/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
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
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.
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Correlative studies
Given IV
Other Names:
Ancillary studies
Other Names:
Given IV
Other Names:
Given IA
Other Names:
Given IA
Other Names:
Given IA
Other Names:
Given IV
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Overall survival
Time Frame: 1 year
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1 year
|
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Response rate
Time Frame: 1 year
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1 year
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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
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4 weeks
|
|
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.
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1 year
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Time to best response
Time Frame: 1 year
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1 year
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Functional outcomes
Time Frame: 1 year
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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.
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1 year
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Incidence of severe neutropenia (specifically febrile neutropenia or sepsis) in accordance with NCI CTC (version 3.0)
Time Frame: 1 year
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Incidence rates of grade III/IV events and associated 95% confidence intervals will be estimated.
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1 year
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Rates of two year progression free survival (2YPFS) for specific tumor types
Time Frame: 2 years
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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.
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2 years
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Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Edward A Neuwelt, OHSU Knight Cancer Institute
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Neoplasms by Histologic Type
- Neoplasms
- Neoplasms, Glandular and Epithelial
- Neoplasms, Neuroepithelial
- Neuroectodermal Tumors
- Neoplasms, Germ Cell and Embryonal
- Neoplasms, Nerve Tissue
- Glioma
- Oligodendroglioma
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Enzyme Inhibitors
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Tubulin Modulators
- Antimitotic Agents
- Mitosis Modulators
- Protective Agents
- Antineoplastic Agents, Alkylating
- Alkylating Agents
- Myeloablative Agonists
- Antineoplastic Agents, Phytogenic
- Topoisomerase II Inhibitors
- Topoisomerase Inhibitors
- Natriuretic Agents
- Dermatologic Agents
- Anti-Bacterial Agents
- Diuretics, Osmotic
- Diuretics
- Keratolytic Agents
- Antioxidants
- Antitubercular Agents
- Chelating Agents
- Sequestering Agents
- Carboplatin
- Etoposide
- Etoposide phosphate
- Mannitol
- Podophyllotoxin
- Melphalan
- Mechlorethamine
- Nitrogen Mustard Compounds
- Sodium thiosulfate
- Antidotes
Other Study ID Numbers
- IRB00002868 (Other Identifier: OHSU Knight Cancer Institute)
- 2868
- NCI-2013-00786 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
- CR00002456
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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