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Central Nervous System Embryonal NeoplasmPhase 1/2NCT00983398

Melphalan, Carboplatin, Mannitol, and Sodium Thiosulfate in Treating Patients With Recurrent or Progressive CNS Embryonal or Germ Cell Tumors

A Phase 1/2 study testing Carboplatin, Mannitol and Melphalan in people with Central Nervous System Embryonal Neoplasm and Embryonal Tumor With Multilayered Rosettes, C19MC-Altered, run by OHSU Knight Cancer Institute at 2 sites in United States.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

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, mannitol, and sodium thiosulfate, and to see how well they work in treating patients with central nervous system (CNS) embryonal or germ cell tumors that is growing, spreading, or getting worse (progressive)… Read more about this study

Who is it for?
Ages 18 to 45 years
What is being tested?
Carboplatin, Mannitol and Melphalan
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
17 participants
Where
2 sitesUnited States
Study dates
9 Jul 2009to 31 Dec 2022
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 45 years
  • All sexes
  • No healthy volunteers
  • Adult

Who may be able to join

  • Subjects with histologically confirmed CNS embryonal tumor (primitive neuroectodermal tumor [PNET], medulloblastoma, atypical teratoid rhabdoid tumor [ATRT], medulloepithelioma, pineoblastoma or ependymoblastoma), or germ cell tumor, are eligible; subjects may be enrolled on study as first-line treatment; diagnosis will be made on the basis of computed tomography (CT)-assisted or stereotactic biopsy, open biopsy, surgical resection, cerebrospinal fluid (CSF) cytology, or elevated tumor markers
  • Subjects may be enrolled as part of first-line treatment; those subjects who enroll as first-line treatment will not be restricted from traditional treatments in the future; at least 14 days must have elapsed since completion of cranial radiotherapy and 28 days since completion of chemotherapy; at least 28 days must have elapsed since completion of total spine radiotherapy
  • Subjects with no previous radiotherapy treatment must have a consultation with a radiation oncologist or providers must have a discussion in the context of Neuro-Oncology Tumor Board within 60 days prior to start of IA/BBBD chemotherapy to determine the need for radiotherapy prior to or after IA/BBBD
  • Glomerular filtration rate (GFR) or creatinine clearance (CrCl) (24 hour urine) greater than 30 ml/min corrected for body surface area
  • Absolute granulocyte count >= 1.0 x 10^3/mm^3
  • Platelets >= 100 x 10^3/mm^3
Show all 13Show fewer
  • Creatinine < 1.5
  • Total bilirubin < 2.0 mg/dl
  • Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) < 2.5 x upper limits of normal
  • Subject's Karnofsky performance status (KPS) must be >= 50% (Eastern Cooperative Oncology Group [ECOG] performance score < 3)
  • Subjects or their legal guardian 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 female become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
  • For the phase II portion of the study, subjects must have disease that is evaluable for response; subjects who have had radiation to all sites of disease are not eligible unless there is imaging evidence of active tumor, ie: increased blood volume

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 with general anesthesia
  • Subjects with uncontrolled (over the last 30 days) clinically significant confounding medical conditions
  • Subject is pregnant or is lactating
  • Subjects who have contraindications to carboplatin, melphalan, or STS

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 Intra-Arterial Melphalan Given With Intra-Arterial Carboplatin, Osmotic Blood-Brain Barrier Disruption and Delayed Otoprotective Sodium Thiosulfate for Patients With Recurrent or Progressive CNS Embryonal or Germ Cell Tumors

This phase I/II trial studies the side effects and best dose of melphalan when given together with carboplatin, mannitol, and sodium thiosulfate, and to see how well they work in treating patients with central nervous system (CNS) embryonal or germ cell tumors that is growing, spreading, or getting worse (progressive) or has come back (recurrent). Drugs used in chemotherapy, such as melphalan and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, 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 melphalan together with carboplatin, mannitol, and sodium thiosulfate may be an effective treatment for recurrent or progressive CNS embryonal or germ cell tumors.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To determine the maximum tolerated dose (MTD) of intra-arterial (IA) melphalan given with IA carboplatin, osmotic BBBD and delayed intravenous (IV) sodium thiosulfate (STS) in subjects with recurrent or progressive embryonal and germ cell tumors of the CNS. (Phase I) II. To estimate the response rate in subjects with recurrent or progressive CNS embryonal and germ cell tumors treated with IA carboplatin, IA melphalan, osmotic BBBD and delayed IV STS. (Phase II)

SECONDARY OBJECTIVES:

  1. To describe 2-year progression-free survival (PFS) and overall survival (OS) rates in subjects with recurrent or progressive CNS embryonal and germ cell tumors treated with IA carboplatin, IA melphalan, osmotic BBBD and delayed IV STS. (Phase II) II. To describe neuropsychological and audiology outcomes in subjects with recurrent or progressive CNS embryonal and germ cell tumors treated with IA carboplatin, IA melphalan, osmotic BBBD and delayed IV STS. (Phase II) III. To describe the overall toxicity of IA carboplatin and IA melphalan in conjunction with osmotic BBBD and delayed STS chemoprotection in subjects with recurrent or progressive CNS embryonal or germ cell tumors. (Phase II)

OUTLINE: This is a phase I, dose-escalation study of melphalan followed by a phase II study.

Patients receive mannitol IA over 30 seconds, melphalan IA over 10 minutes, and carboplatin IA over 10 minutes. Patients then receive sodium thiosulfate IV over 15 minutes at 4 and 8 hours after carboplatin. Treatment repeats every 4-6 weeks for up to 12 cycles in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for 1 year, every 6 months for 1 year, and then annually for 3 years.

Being tested
Carboplatin, Mannitol, Melphalan, Quality-of-Life Assessment, Questionnaire Administration
Medical subject headings
Neuroectodermal Tumors, Primitive, Neoplasms, Germ Cell and Embryonal, Medulloblastoma

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

  • 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

  • Questionnaire AdministrationOther

    Ancillary studies

  • Sodium ThiosulfateDrug

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

    Given IV

Study groups in NCT00983398
Study groupRoleWhat they receive
Treatment (mannitol, melphalan, carboplatin, STS)ExperimentalPatients receive mannitol IA over 30 seconds, melphalan IA over 10 minutes, and carboplatin IA over 10 minutes. Patients then receive sodium thiosulfate IV over 15 minutes at 4 and 8 hours after carboplatin. Treatment repeats every 4-6 weeks for up to 12 cycles in the absence of disease progression or unacceptable toxicity.
Receives: Drug: Carboplatin; Drug: Mannitol; Drug: Melphalan; Other: Quality-of-Life Assessment; Other: Questionnaire Administration; Drug: Sodium Thiosulfate

What is being measured

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

  1. Maximum tolerated dose (Phase I)

    Will be assessed based on the incidence of dose-limiting toxicity, graded using the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0. All toxicities will be tabulated by event and by overall. The toxicities will also be tabulated by highest grade. The recovery from toxicities (i.e. hematologic toxicities) will also be summarized.

    Measured: 6 weeks

  2. Response rate (Phase II)

    Descriptive statistics will be estimated.

    Measured: Up to 5 years

Secondary outcomes (4)

  1. Progression free survival rate (Phase II)

    Estimation made using Kaplan-Meier product limit estimation. A Cox proportional hazards regression model will be fit to the data to estimate the association of progression free survival and overall survival with baseline demographic and disease characteristics.

    Measured: Time from first study treatment to evidence of first progression, assessed at 2 years

  2. Overall survival rate (Phase II)

    Estimation made using Kaplan-Meier product limit estimation. A Cox proportional hazards regression model will be fit to the data to estimate the association of progression free survival and overall survival with baseline demographic and disease characteristics.

    Measured: Time from time of first study treatment until death, assessed at 2 years

  3. Change in neurocognitive assessment scores (Phase II)

    Quantitative scores, whenever possible, will be derived from each measure and converted to measure-specific Z scores using normative data. Post-treatment Z scores will be subtracted from pre-treatment Z scores to calculate absolute change in neuropsychological test performance. Significant change will be defined as change of 1 standard deviation. These data will be summarized descriptively.

    Measured: Baseline to 90 days after completion of study treatment

  4. Proportion of patients with ototoxicity (Phase II)

    Will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0. Estimated using proportions with associated confidence intervals.

    Measured: Up to 30 days after completion of study treatment

Timeline

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

  1. First posted24 Sep 2009 (estimated)
  2. Study start9 Jul 2009
  3. Primary completion31 Dec 2021 (estimated)
  4. Study completion31 Dec 2022 (estimated)

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
17 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00983398
Sponsor's protocol ID
IRB00005056
Other IDs
NCI-2013-00790, OHSU-5056, MR00042551, 5056, IRB00005056, R01NS044687
Status last verified
Oct 2021
First submitted
23 Sep 2009
Last updated
26 Oct 2021
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Carboplatin, Mannitol and Melphalan in people with Central Nervous System Embryonal Neoplasm and Embryonal Tumor With Multilayered Rosettes, C19MC-Altered, 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: status not confirmed, as of the sponsor's last update on 26 Oct 2021. 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?

Results are not available in the source record.

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?

Maximum tolerated dose (Phase I) (time frame: 6 weeks). The study lists 2 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 NCT00983398.

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 26 Oct 2021.

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