Malignant GliomaPhase 2NCT00075387
Combination Chemotherapy With or Without Sodium Thiosulfate in Preventing Low Platelet Count While Treating Patients With Malignant Brain Tumors
A Phase 2 study testing Carboplatin, Cyclophosphamide and Etoposide Phosphate in people with Malignant Glioma, run by OHSU Knight Cancer Institute at 3 sites in United States.
Trial summary
This randomized phase II trial studies how well giving combination chemotherapy with or without sodium thiosulfate works in preventing low platelet count while treating patients with malignant brain tumors. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Malignant Glioma
- What is being tested?
- Carboplatin, Cyclophosphamide and Etoposide Phosphate
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 48 participants
- Where
- 3 sitesUnited States
- Study dates
- 7 Mar 2003to 30 Apr 2024
- Phase
- Phase 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 histologically confirmed high-grade glioma are eligible; diagnosis of high-grade glioma will be made on the basis of needle biopsy, open biopsy, or surgical resection
- Subjects may have had prior focal or systemic radiation or chemotherapy; at least 14 days must have elapsed since radiation treatment and 28 days since prior chemotherapy
- Performance status (Eastern Cooperative Oncology Group [ECOG]) must be less than or equal to 2 (Karnofsky greater than or equal to 50)
- White blood cell count >= 2.5 x 10^3/mm^3
- Absolute granulocyte count >= 1.2 x 10^3/mm^3
- Platelets >= 100 x 10^3/mm^3
Show all 11Show fewer
- Creatinine < 1.8
- Bilirubin < 2.0
- Baseline aspartate aminotransferase (AST)/alanine aminotransferase (ALT) serum glutamic oxaloacetic transaminase (SGOT)/serum glutamate pyruvate transaminase (SGPT) must be < 2.5 x institutional upper limits of normal
- Subject (or 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; or 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 the investigator
Who cannot join
- Subjects with rapidly progressing central nervous system (CNS) disease with associated neurological deterioration
- Subjects with uncontrolled (over the last 30 days) clinically significant confounding medical conditions such as congestive heart failure
- Subjects who are pregnant, have a positive serum human chorionic gonadotropin (hCG) or are lactating
- Subjects who have contraindications to carboplatin, cyclophosphamide, etoposide phosphate, or sodium thiosulfate
Trial locations and contacts
3 sites in 1 country.
United States3 sites
Cleveland Clinic Foundation
Cleveland, Ohio, 44195
University of Minnesota/Masonic Cancer Center
Minneapolis, Minnesota, 55455
OHSU Knight Cancer Institute
Portland, Oregon, 97239
About this study
Official title: Phase II Clinical Trial of Patients With High-Grade Glioma Treated With Intra-Arterial Carboplatin-Based Chemotherapy, Randomized to Treatment With or Without Delayed Intravenous Sodium Thiosulfate as a Potential Chemoprotectant Against Severe Thrombocytopenia
This randomized phase II trial studies how well giving combination chemotherapy with or without sodium thiosulfate works in preventing low platelet count while treating patients with malignant brain tumors. Drugs used in chemotherapy, such as carboplatin, cyclophosphamide, and etoposide phosphate, 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. Sodium thiosulfate may prevent low platelet counts in patients receiving chemotherapy. It is not yet known whether combination chemotherapy is more effective with or without sodium thiosulfate in preventing low platelet count during treatment for brain tumors.
Read the detailed description
PRIMARY OBJECTIVE:
- Determine the effect of delayed administration of sodium thiosulfate on the rates of platelet toxicity (i.e. platelet count less than 20,000), in subjects with high-grade glioma undergoing treatment with carboplatin, cyclophosphamide and etoposide/etoposide phosphate.
SECONDARY OBJECTIVES:
- Assess tumor response in subjects with high-grade glioma undergoing treatment with carboplatin, cyclophosphamide and etoposide/etoposide phosphate, with or without delayed sodium thiosulfate.
II. Assess the effect of delayed administration of sodium thiosulfate on granulocyte and erythrocyte counts, in subjects undergoing treatment with carboplatin, cyclophosphamide and etoposide/etoposide phosphate.
III. Assess hearing changes, if any, at the higher frequencies in the standard testing range (4000 and 8000 Hertz [Hz]), and at higher frequencies above standard testing (9000 to 16000 Hz).
IV. Assess quality of life in subjects undergoing treatment with carboplatin, cyclophosphamide and etoposide phosphate.
OUTLINE: Patients are randomized to 1 of 2 treatment arms.
ARM I: Patients receive cyclophosphamide intravenously (IV), etoposide phosphate IV, and carboplatin intra-arterially (IA) over 10 minutes on day 1.
ARM II: Patients receive cyclophosphamide IV, etoposide phosphate IV, and carboplatin IA as in Arm I. Patients also receive sodium thiosulfate IV over 15 minutes 4 and 8 hours after carboplatin.
In both arms, treatment repeats every 4 weeks for up to 12 courses 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 2 years, and then annually thereafter.
- Conditions
- Malignant Glioma
- Being tested
- Carboplatin, Cyclophosphamide, Etoposide Phosphate, Quality-of-Life Assessment, Sodium Thiosulfate
- Medical subject headings
- Glioma
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
CyclophosphamideDrug
Also called (-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Carloxan, Ciclofosfamida
Given IV
Etoposide PhosphateDrug
Also called Etopophos
Given IV
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 group | Role | What they receive |
|---|---|---|
| Arm I (combination chemotherapy) | Experimental | Patients receive cyclophosphamide IV, etoposide phosphate IV, and carboplatin IA over 10 minutes.
Treatment repeats every 4 weeks for up to 12 courses in the absence of disease progression or unacceptable toxicity. Receives: Drug: Carboplatin; Drug: Cyclophosphamide; Drug: Etoposide Phosphate; Other: Quality-of-Life Assessment |
| Arm II (combination chemotherapy, sodium thiosulfate) | Experimental | Patients receive cyclophosphamide IV, etoposide phosphate IV, and carboplatin IA as in Arm I. Patients also receive sodium thiosulfate IV over 15 minutes 4 and 8 hours later.
Treatment repeats every 4 weeks for up to 12 courses in the absence of disease progression or unacceptable toxicity. Receives: Drug: Carboplatin; Drug: Cyclophosphamide; Drug: Etoposide Phosphate; 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.
Rate of platelet toxicities (i.e. platelet count less than 20,000), graded according to the National Cancer Institute Common Toxicity Criteria version 3.0
The Pearson chi-square test will be the primary test to compare rates.
Measured: Up to 4 weeks after completion of study treatment
Secondary outcomes (8)
Number of dose reductions and transfusions due to platelet toxicity
Analyzed using generalized estimating equations and/or a generalized mixed model (for repeated measures analysis of variance) and the third using mixed model repeated measures analysis of variance model.
Measured: Up to 30 days after completion of study treatment
Tumor response (complete response + partial response + stable disease) assessed by neurologic exams, radiographic studies, and steroid dose
The Pearson chi-square test will be the primary test to compare rates. Comparisons of rates will use the Pearson Chi-square test and logistic regression to adjust for potential confounders.
Measured: Up to 10 years
Time to response
Descriptive summaries include Kaplan-Meier plots.
Measured: Up to 10 years
Time to disease progression
Comparisons of time to disease progression will use the log rank test and the Cox proportional hazards model to adjust for potential confounders.
Measured: Up to 10 years
Granulocyte count
The Pearson chi-square test will be the primary test to compare rates.
Measured: Up to 30 days after completion of study treatment
Erythrocyte counts
The Pearson chi-square test will be the primary test to compare rates.
Measured: Up to 30 days after completion of study treatment
Change in hearing levels, if any, at the higher frequencies in the standard testing range (4000 and 8000 Hz), and at higher frequencies above standard testing (9000 to 16000 Hz) based on American Speech-Language-Hearing Association criteria
Descriptive summaries for hearing levels will include means by time and plots of hearing levels by patient over time. The analyses for hearing will include both a time to oto-toxicity (based on American Speech-Language-Hearing Association criteria) comparison using the log rank test and a repeated measure analysis of covariance of the actual hearing levels (with baseline hearing levels as the covariate). Separate analyses will be performed for each hearing frequency with no adjustment for multiple comparisons (as these analyses are descriptive in nature).
Measured: Baseline up to 30 days after completion of study treatment
Quality of life assessed by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 and Quality of Life Questionnaire-Brain Module-20
Summarized by means over time and by plots of values over time for each patient. Quality of life data comparisons between the groups will use repeated measure analysis of covariance (baseline assessment as the covariate).
Measured: Up to 60 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.
- First posted12 Jan 2004 (estimated)
- Study start7 Mar 2003
- Primary completion30 Apr 2023 (estimated)
- Study completion30 Apr 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Malignant GliomaStudies of the same condition, open and under way.
- More trials run by OHSU Knight Cancer InstituteThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Investigator
- Enrolment
- 48 participants (actual)
Sponsor and investigators
- Lead sponsor
- OHSU Knight Cancer Institute
- Sponsor type
- University, hospital or other
- Collaborators
- Oregon Health and Science University
- Responsible party
- Principal investigator, Edward Neuwelt, OHSU Knight Cancer Institute
- Investigators
- Edward A Neuwelt, Principal investigator, OHSU Knight Cancer Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00075387
- Sponsor's protocol ID
- IRB00000922
- Other IDs
- NCI-2013-00781, eIRB #922, ONC-02019-L, CR00023930, MR00041590, CR00021317, CR00018679, CR00022743
- Status last verified
- Apr 2022
- First submitted
- 9 Jan 2004
- Last updated
- 3 May 2022
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 3 May 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Clinical Trial of Patients With High-Grade Glioma Treated With Intra-Arterial Carboplatin-Based Chemotherapy, Randomized to Treatment With or Without Delayed Intravenous Sodium Thiosulfate as a Potential Chemoprotectant Against Severe Thrombocytopenia
- ClinicalTrials.gov ID
- NCT00075387
- Acronym / sponsor ID
- IRB00000922
- Conditions
- Malignant Glioma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 48 participants (actual)
- Lead sponsor
- OHSU Knight Cancer InstituteUniversity, hospital or other
- Collaborators
- Oregon Health and Science University
- Study start
- 7 Mar 2003 (actual)
- Primary completion
- 30 Apr 2023 (estimated)
- Study completion
- 30 Apr 2024 (estimated)
- First posted
- 12 Jan 2004 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This randomized phase II trial studies how well giving combination chemotherapy with or without sodium thiosulfate works in preventing low platelet count while treating patients with malignant brain tumors. Drugs used in chemotherapy, such as carboplatin, cyclophosphamide, and etoposide phosphate, 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. Sodium thiosulfate may prevent low platelet counts in patients receiving chemotherapy. It is not yet known whether combination chemotherapy is more effective with or without sodium thiosulfate in preventing low platelet count during treatment for brain tumors.
Detailed description
PRIMARY OBJECTIVE:
- Determine the effect of delayed administration of sodium thiosulfate on the rates of platelet toxicity (i.e. platelet count less than 20,000), in subjects with high-grade glioma undergoing treatment with carboplatin, cyclophosphamide and etoposide/etoposide phosphate.
SECONDARY OBJECTIVES:
- Assess tumor response in subjects with high-grade glioma undergoing treatment with carboplatin, cyclophosphamide and etoposide/etoposide phosphate, with or without delayed sodium thiosulfate.
II. Assess the effect of delayed administration of sodium thiosulfate on granulocyte and erythrocyte counts, in subjects undergoing treatment with carboplatin, cyclophosphamide and etoposide/etoposide phosphate.
III. Assess hearing changes, if any, at the higher frequencies in the standard testing range (4000 and 8000 Hertz [Hz]), and at higher frequencies above standard testing (9000 to 16000 Hz).
IV. Assess quality of life in subjects undergoing treatment with carboplatin, cyclophosphamide and etoposide phosphate.
OUTLINE: Patients are randomized to 1 of 2 treatment arms.
ARM I: Patients receive cyclophosphamide intravenously (IV), etoposide phosphate IV, and carboplatin intra-arterially (IA) over 10 minutes on day 1.
ARM II: Patients receive cyclophosphamide IV, etoposide phosphate IV, and carboplatin IA as in Arm I. Patients also receive sodium thiosulfate IV over 15 minutes 4 and 8 hours after carboplatin.
In both arms, treatment repeats every 4 weeks for up to 12 courses 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 2 years, and then annually thereafter.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm I (combination chemotherapy) | Experimental | Drug: Carboplatin, Drug: Cyclophosphamide, Drug: Etoposide Phosphate, Other: Quality-of-Life AssessmentPatients receive cyclophosphamide IV, etoposide phosphate IV, and carboplatin IA over 10 minutes. Treatment repeats every 4 weeks for up to 12 courses in the absence of disease progression or unacceptable toxicity. |
| Arm II (combination chemotherapy, sodium thiosulfate) | Experimental | Drug: Carboplatin, Drug: Cyclophosphamide, Drug: Etoposide Phosphate, Other: Quality-of-Life Assessment, Drug: Sodium ThiosulfatePatients receive cyclophosphamide IV, etoposide phosphate IV, and carboplatin IA as in Arm I. Patients also receive sodium thiosulfate IV over 15 minutes 4 and 8 hours later. Treatment repeats every 4 weeks for up to 12 courses in the absence of disease progression or unacceptable toxicity. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Subjects with histologically confirmed high-grade glioma are eligible; diagnosis of high-grade glioma will be made on the basis of needle biopsy, open biopsy, or surgical resection
- Subjects may have had prior focal or systemic radiation or chemotherapy; at least 14 days must have elapsed since radiation treatment and 28 days since prior chemotherapy
- Performance status (Eastern Cooperative Oncology Group [ECOG]) must be less than or equal to 2 (Karnofsky greater than or equal to 50)
- White blood cell count >= 2.5 x 10^3/mm^3
- Absolute granulocyte count >= 1.2 x 10^3/mm^3
Key exclusion criteria (4 listed)
- Subjects with rapidly progressing central nervous system (CNS) disease with associated neurological deterioration
- Subjects with uncontrolled (over the last 30 days) clinically significant confounding medical conditions such as congestive heart failure
- Subjects who are pregnant, have a positive serum human chorionic gonadotropin (hCG) or are lactating
- Subjects who have contraindications to carboplatin, cyclophosphamide, etoposide phosphate, or sodium thiosulfate
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CarboplatinAlso: Blastocarb, Carboplat, Carboplatin Hexal, CarboplatinoGiven IA | Drug | Arm I (combination chemotherapy), Arm II (combination chemotherapy, sodium thiosulfate) |
| CyclophosphamideAlso: (-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Carloxan, CiclofosfamidaGiven IV | Drug | Arm I (combination chemotherapy), Arm II (combination chemotherapy, sodium thiosulfate) |
| Etoposide PhosphateAlso: EtopophosGiven IV | Drug | Arm I (combination chemotherapy), Arm II (combination chemotherapy, sodium thiosulfate) |
| Quality-of-Life AssessmentAlso: Quality of Life AssessmentAncillary studies | Other | Arm I (combination chemotherapy), Arm II (combination chemotherapy, sodium thiosulfate) |
| Sodium ThiosulfateAlso: Cyanide Antidote Package, Disodium Thiosulfate, S-Hydril, Sodium HyposulfateGiven IV | Drug | Arm II (combination chemotherapy, sodium thiosulfate) |
Primary outcome
Rate of platelet toxicities (i.e. platelet count less than 20,000), graded according to the National Cancer Institute Common Toxicity Criteria version 3.0
Time frame: Up to 4 weeks after completion of study treatment
The Pearson chi-square test will be the primary test to compare rates.
8 secondary outcomes
Number of dose reductions and transfusions due to platelet toxicity
Time frame: Up to 30 days after completion of study treatment
Tumor response (complete response + partial response + stable disease) assessed by neurologic exams, radiographic studies, and steroid dose
Time frame: Up to 10 years
Time to response
Time frame: Up to 10 years
Time to disease progression
Time frame: Up to 10 years
Granulocyte count
Time frame: Up to 30 days after completion of study treatment
Erythrocyte counts
Time frame: Up to 30 days after completion of study treatment
Change in hearing levels, if any, at the higher frequencies in the standard testing range (4000 and 8000 Hz), and at higher frequencies above standard testing (9000 to 16000 Hz) based on American Speech-Language-Hearing Association criteria
Time frame: Baseline up to 30 days after completion of study treatment
Quality of life assessed by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 and Quality of Life Questionnaire-Brain Module-20
Time frame: Up to 60 days after completion of study treatment
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 May 2022.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Edward A Neuwelt principal investigator
OHSU Knight Cancer Institute
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Carboplatin, Cyclophosphamide and Etoposide Phosphate in people with Malignant Glioma, run by OHSU Knight Cancer Institute at 3 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 11 inclusion and 4 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 3 May 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 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 phase mean?
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?
Rate of platelet toxicities (i.e. platelet count less than 20,000), graded according to the National Cancer Institute Common Toxicity Criteria version 3.0 (time frame: Up to 4 weeks after completion of study treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 3 May 2022.