Combination Chemotherapy With or Without Sodium Thiosulfate in Preventing Low Platelet Count While Treating Patients With Malignant Brain Tumors
|
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. |
| ClinicalTrials.gov Identifier: NCT00075387 |
|
Recruitment Status :
Recruiting
First Posted : January 12, 2004
Last Update Posted : May 7, 2018
|
- Study Details
- Tabular View
- No Results Posted
- Disclaimer
- How to Read a Study Record
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Glioma | Drug: Carboplatin Drug: Cyclophosphamide Drug: Etoposide Phosphate Other: Quality-of-Life Assessment Drug: Sodium Thiosulfate | Phase 2 |
PRIMARY OBJECTIVES:
I. 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:
I. 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 Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 60 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | Single (Investigator) |
| Primary Purpose: | Treatment |
| 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 |
| Actual Study Start Date : | March 7, 2003 |
| Estimated Primary Completion Date : | April 30, 2020 |
| Estimated Study Completion Date : | April 30, 2021 |
| Arm | Intervention/treatment |
|---|---|
|
Experimental: Arm I (combination chemotherapy)
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. |
Drug: Carboplatin
Given IA
Other Names:
Drug: Cyclophosphamide
Given IV
Other Names:
Drug: Etoposide Phosphate
Given IV
Other Name: Etopophos
Other: Quality-of-Life Assessment
Ancillary studies
Other Name: Quality of Life Assessment
|
|
Experimental: Arm II (combination chemotherapy, sodium thiosulfate)
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. |
Drug: Carboplatin
Given IA
Other Names:
Drug: Cyclophosphamide
Given IV
Other Names:
Drug: Etoposide Phosphate
Given IV
Other Name: Etopophos
Other: Quality-of-Life Assessment
Ancillary studies
Other Name: Quality of Life Assessment
Drug: Sodium Thiosulfate
Given IV
Other Names:
|
- 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.
- 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 ]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).
- Erythrocyte counts [ Time Frame: Up to 30 days after completion of study treatment ]The Pearson chi-square test will be the primary test to compare rates.
- Granulocyte count [ Time Frame: Up to 30 days after completion of study treatment ]The Pearson chi-square test will be the primary test to compare rates.
- Number of dose reductions and transfusions due to platelet toxicity [ Time Frame: Up to 30 days after completion of study treatment ]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.
- 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 ]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).
- Time to disease progression [ Time Frame: Up to 10 years ]Comparisons of time to disease progression will use the log rank test and the Cox proportional hazards model to adjust for potential confounders.
- Time to response [ Time Frame: Up to 10 years ]Descriptive summaries include Kaplan-Meier plots.
- Tumor response (complete response + partial response + stable disease) assessed by neurologic exams, radiographic studies, and steroid dose [ Time Frame: Up to 10 years ]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.
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, Learn About Clinical Studies.
| Ages Eligible for Study: | 18 Years to 75 Years (Adult, Senior) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- 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
- 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
Exclusion Criteria:
- 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
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00075387
| United States, Minnesota | |
| University of Minnesota/Masonic Cancer Center | Active, not recruiting |
| Minneapolis, Minnesota, United States, 55455 | |
| United States, Ohio | |
| Cleveland Clinic Foundation | Active, not recruiting |
| Cleveland, Ohio, United States, 44195 | |
| United States, Oregon | |
| OHSU Knight Cancer Institute | Recruiting |
| Portland, Oregon, United States, 97239 | |
| Contact: Edward A. Neuwelt 503-494-5626 neuwelte@ohsu.edu | |
| Principal Investigator: Edward A. Neuwelt | |
| Principal Investigator: | Edward Neuwelt | OHSU Knight Cancer Institute |
| Responsible Party: | Edward Neuwelt, Principal Investigator, OHSU Knight Cancer Institute |
| ClinicalTrials.gov Identifier: | NCT00075387 History of Changes |
| Other Study ID Numbers: |
IRB00000922 NCI-2013-00781 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ) MR00041590 CR00023930 eIRB #922 CR00018679 ONC-02019-L CR00021317 CR00022743 IRB00000922 ( Other Identifier: OHSU Knight Cancer Institute ) P30CA069533 ( U.S. NIH Grant/Contract ) |
| First Posted: | January 12, 2004 Key Record Dates |
| Last Update Posted: | May 7, 2018 |
| Last Verified: | May 2018 |
Additional relevant MeSH terms:
|
Glioma Neoplasms, Neuroepithelial Neuroectodermal Tumors Neoplasms, Germ Cell and Embryonal Neoplasms by Histologic Type Neoplasms Neoplasms, Glandular and Epithelial Neoplasms, Nerve Tissue Cyclophosphamide Etoposide phosphate Carboplatin Etoposide Sodium thiosulfate Immunosuppressive Agents Immunologic Factors |
Physiological Effects of Drugs Antirheumatic Agents Antineoplastic Agents, Alkylating Alkylating Agents Molecular Mechanisms of Pharmacological Action Antineoplastic Agents Myeloablative Agonists Antineoplastic Agents, Phytogenic Topoisomerase II Inhibitors Topoisomerase Inhibitors Enzyme Inhibitors Antidotes Protective Agents Antioxidants Antitubercular Agents |