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Anaplastic OligoastrocytomaPhase 1/2NCT00303849

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

A Phase 1/2 study testing Carboplatin, Etoposide and Etoposide Phosphate in people with Anaplastic Oligoastrocytoma and Anaplastic Oligodendroglioma, run by OHSU Knight Cancer Institute at 2 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 75 years
What is being tested?
Carboplatin, Etoposide and Etoposide Phosphate
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
33 participants
Where
2 sitesUnited States
Study dates
15 Sep 2005to 12 Mar 2021
Phase
Phase 1/2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 75 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
Show all 13Show fewer
  • 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

Who cannot join

  • 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

Trial locations and contacts

2 sites in 1 country.

United States2 sites

  • University of Minnesota/Masonic Cancer Center

    Minneapolis, Minnesota, 55455

  • OHSU Knight Cancer Institute

    Portland, Oregon, 97239

Other trials in United States

About this study

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

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.

Read the detailed description

PRIMARY OBJECTIVES:

  1. 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:

  1. 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.

  1. 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.

Being tested
Carboplatin, Etoposide, Etoposide Phosphate, Laboratory Biomarker Analysis, Mannitol
Medical subject headings
Oligodendroglioma, Glioma, Astrocytoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CarboplatinDrug

    Also called Blastocarb, Carboplat, Carboplatin Hexal, Carboplatino

    Given IA

  • EtoposideDrug

    Also called Demethyl Epipodophyllotoxin Ethylidine Glucoside, EPEG, Lastet, Toposar

    Given IV

  • Etoposide PhosphateDrug

    Also called Etopophos

    Given IV

  • Laboratory Biomarker AnalysisOther

    Correlative studies

  • MannitolDrug

    Also called D-Mannitol, Mannitol, D-, Osmitrol, Resectisol

    Given IA

  • MelphalanDrug

    Also called Alanine Nitrogen Mustard, CB-3025, L-PAM, L-Phenylalanine mustard

    Given IA

  • Quality-of-Life AssessmentOther

    Also called Quality of Life Assessment

    Ancillary studies

  • Sodium ThiosulfateDrug

    Also called Cyanide Antidote Package, Disodium Thiosulfate, S-Hydril, Sodium Hyposulfate

    Given IV

Study groups in NCT00303849
Study groupRoleWhat they receive
Treatment (etoposide, mannitol, melphalan, carboplatin, STS)ExperimentalPatients 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.
Receives: Drug: Carboplatin; Drug: Etoposide; Drug: Etoposide Phosphate; Other: Laboratory Biomarker Analysis; Drug: Mannitol; Drug: Melphalan; Other: Quality-of-Life Assessment; Drug: Sodium Thiosulfate

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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)

    Measured: 4 weeks

  2. Overall survival

    Measured: 1 year

  3. Progression free survival (Phase II)

    Kaplan-Meier method will be used. 95% confidence intervals estimated. Cox proportional hazards regression models will be fit to explore potential predictors.

    Measured: 1 year

  4. Response rate

    Measured: 1 year

  5. Time to best response

    Measured: 1 year

Secondary outcomes (3)

  1. Functional outcomes

    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.

    Measured: 1 year

  2. Incidence of severe neutropenia (specifically febrile neutropenia or sepsis) in accordance with NCI CTC (version 3.0)

    Incidence rates of grade III/IV events and associated 95% confidence intervals will be estimated.

    Measured: 1 year

  3. Rates of two year progression free survival (2YPFS) for specific tumor types

    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.

    Measured: 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted17 Mar 2006 (estimated)
  2. Study start15 Sep 2005
  3. Primary completion12 Mar 2021
  4. Study completion12 Mar 2021

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
33 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00303849
Sponsor's protocol ID
IRB00002868
Other IDs
NCI-2013-00786, CR00002456, 2868, IRB00002868
Status last verified
Mar 2022
First submitted
15 Mar 2006
Last updated
17 Mar 2022
Results posted
No
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Carboplatin, Etoposide and Etoposide Phosphate in people with Anaplastic Oligoastrocytoma and Anaplastic Oligodendroglioma, run by OHSU Knight Cancer Institute at 2 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 13 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 17 Mar 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00303849.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Mar 2022.

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