Brain and Central Nervous System TumorsPhase 1/2NCT00275067
Arsenic Trioxide, Temozolomide, and Radiation Therapy in Treating Patients With Malignant Glioma That Has Been Removed By Surgery
A Phase 1/2 study testing arsenic trioxide, temozolomide and radiation therapy in people with Brain and Central Nervous System Tumors, run by Northwestern University at 3 sites in United States.
Trial summary
RATIONALE: Drugs used in chemotherapy, such as arsenic trioxide and temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Brain and Central Nervous System Tumors
- What is being tested?
- arsenic trioxide, temozolomide and radiation therapy
- Type of treatment
- Pill or oral medicine, Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 3 sitesUnited States
- Study dates
- May 2005to May 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
DISEASE CHARACTERISTICS:
- Histologically confirmed supratentorial malignant glioma of 1 of the following types:
- Glioblastoma multiforme
- Gliosarcoma
- Anaplastic astrocytoma
- Anaplastic oligodendroglioma
- Anaplastic mixed gliomas
- Anaplastic gliomas not otherwise specified
- Has undergone surgical resection of tumor
- Patients with biopsy only are eligible
- Evaluable or measurable disease following resection of recurrent tumor is not mandated for entry into the study
- No brain metastases
PATIENT CHARACTERISTICS:
- Karnofsky performance status 60-100%
- Life expectancy > 3 months
- WBC > 3,000/mm^3
- Absolute neutrophil count > 2,000/mm^3
- Platelet count > 100,000/mm^3
- Hemoglobin > 10 g/dL (eligibility level for hemoglobin may be reached by transfusion)
- Creatinine ≤ 1.5 mg/dL
- Bilirubin ≤ 2 mg/dL
- Transaminases ≤ 2 times the upper limit of normal
- Serum potassium* > 4.0 mEq/dL
- Serum magnesium* > 1.8 mg/dL NOTE: *If these serum electrolytes are below the specified limits on the baseline laboratory tests, supplemental electrolytes should be administered to bring the serum concentrations to these levels before administering arsenic trioxide
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception during and for 3 months after completion of study treatment
- No second-degree heart block
- QT interval ≤ 460 msec
- No other malignancy within the past 3 years except curatively treated carcinoma in situ or basal cell carcinoma of the skin
- Patients who cannot undergo MRI are not eligible for this study
- No other serious concurrent infection or other medical illness that would jeopardize the ability of the patient to receive the therapy in this protocol with reasonable safety
PRIOR CONCURRENT THERAPY:
- See Disease Characteristics
- Patients must have recovered from the effects of surgery prior to the start of treatment (10-14 days minimum) and be maintained on a stable corticosteroid regimen for 5 days
- Concurrent glucocorticoid therapy allowed at the smallest effective dose
- Patients must be on non-enzyme-inducing anti-convulsants to minimize any drug reaction
- No prior radiation therapy, chemotherapy, immunotherapy, therapy with biologic agents (including immunotoxins, immunoconjugates, antisense agents, peptide receptor antagonists, interferons, interleukins, tumor-infiltrating lymphocytes, lymphokine-activated killer cells, or gene therapy), or hormonal therapy for their brain tumor
Trial locations and contacts
3 sites in 1 country.
United States3 sites
Hematology-Oncology Associates of Illinois
Chicago, Illinois, 60611-2998
Robert H. Lurie Comprehensive Cancer Center at Northwestern University
Chicago, Illinois, 60611-3013
Edward Cancer Center
Naperville, Illinois, 60540
About this study
Official title: A Phase I/II Trial of Arsenic Trioxide and Temozolomide in Combination With Radiation Therapy for Patients With Malignant Gliomas
RATIONALE: Drugs used in chemotherapy, such as arsenic trioxide and temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving arsenic trioxide and temozolomide together with radiation therapy after surgery may kill any remaining tumor cells.
PURPOSE: This phase I/II trial is studying the side effects and best dose of arsenic trioxide and temozolomide when given together with radiation therapy and to see how well they work in treating patients with malignant glioma that has been removed by surgery.
Read the detailed description
OBJECTIVES:
Primary
- Determine the maximum tolerated dose (MTD) of arsenic trioxide and temozolomide when combined with radiotherapy in patients with resected supratentorial malignant glioma. (Phase I)
- Determine the toxicity of this regimen in these patients. (Phase I)
Secondary
- Determine the 6- and 12-month progression-free survival of patients treated with this regimen once an MTD is reached. (Phase II)
- Determine the radiographic response for patients treated with the above regimen. (Phase II)
- Determine the safety of this regimen in these patients. (Phase II)
OUTLINE: This is a phase I, dose-escalation study of arsenic trioxide and temozolomide followed by a phase II study.
- Phase I: Patients undergo radiotherapy once daily 5 days a week and receive oral temozolomide once daily for approximately 6½ weeks. Patients also receive arsenic trioxide IV over 1-4 hours once daily, 5 days a week in week 1 and then twice a week in weeks 2-7. Beginning within 3-5 weeks after completion of radiotherapy, patients receive oral temozolomide once daily on days 1-5. Treatment with temozolomide repeats every 28 days for up to 1 year in the absence of disease progression and unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of arsenic trioxide and temozolomide until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 1 of 3 or 2 of 6 patients experience dose-limiting toxicity.
- Phase II: Patients undergo radiotherapy and receive arsenic trioxide and temozolomide as in phase I at the MTD. Patients then receive temozolomide as in phase I for up to 1 year in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed periodically for 1 year.
PROJECTED ACCRUAL: A total of 12-18 patients will be accrued for the phase I portion of this study. A total of 25 patients will be accrued for the phase II portion of this study.
- Conditions
- Brain and Central Nervous System Tumors
- Being tested
- arsenic trioxide, temozolomide, radiation therapy
- Keywords
- adult anaplastic astrocytoma, adult gliosarcoma, adult anaplastic oligodendroglioma, adult mixed glioma, adult glioblastoma, adult giant cell glioblastoma, recurrent adult brain tumor
- Medical subject headings
- Central Nervous System Neoplasms, Astrocytoma, Gliosarcoma, Oligodendroglioma, Glioma, Glioblastoma, Brain Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
arsenic trioxideDrug
Also called ATO, TRISENOX
Arsenic trioxide administered intravenously at a dose of 0.20mg/kg Daily x 5 week then twice per week
temozolomideDrug
Also called TMZ, Temodar
Temozolomide administered orally once per day 1 hour prior to radiation therapy at a dose of 75 mg/m2 x 42 days; at a dose of 200mg/m2 for 5 days every cycle (1 cycle = 28 days) after radiation therapy
radiation therapyRadiation
All patients will receive 5940-6120 cGy of radiation therapy as 28-33 treatments/fractions (180-200 cGy/treatment) depending on whether they receive standard 3-D conformal radiation therapy or intensity modulated radiation therapy.
| Study group | Role | What they receive |
|---|---|---|
| Radiation + temozolomide and arsenic trioxide | Experimental | Radiation therapy followed by the combination of temozolomide and arsenic trioxide at the maximum tolerated dose determined in phase 1 Receives: Drug: arsenic trioxide; Drug: temozolomide; Radiation: radiation therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum tolerated dose of arsenic trioxide and temozolomide in combination with radiotherapy
Escalating doses of study drug until dose limiting toxicities are observed.
Measured: Toxicity evaluated prior to each treatment cycle
Collect data on the toxicity of arsenic and temozolomide during radiation therapy
Toxicity of this drug combination during radiation therapy will be assessed.
Measured: Toxicity evaluated prior to each treatment cycle
Assess serum biomarkers and correlate with tumor tissue
Blood will be drawn at baseline, during radiation therapy, and prior to each cycle of chemotherapy to assess serum biomarkers and correlate with tumor tissue.
Measured: At baseline, during radiation therapy, and prior to each cycle of chemotherapy
Secondary outcomes (6)
Determine progression free survival at 6 and 12 months
Patients will undergo an MRI and neurological evaluation every 6 months while on chemotherapy.
Measured: At 6 and 12 months after beginning chemotherapy
Determine time to disease progression
Disease status will be assessed by MRI and neurological examination every 6 months until disease progression.
Measured: At 6 and 12 months after beginning chemotherapy
To determine overall survival
Survival status will be evaluated every 6 months while on treatment.
Measured: Every 6 months while on treatment
To determine radiographic response to study regimen
Radiographic response will be assessed by MRI every 6 months while on treatment
Measured: Every 6 months while on treatment
To collect safety data during the radiation therapy phase
EKG's will be done once per week and labs twice per week during radiation therapy phase to evaluate safety data.
Measured: Weekly during radiation therapy
To evaluate a potential surrogate marker for outcomes
Blood will be drawn to analyze methylation patterns as a surrogate marker for outcomes at baseline, before and after radiation therapy, and every 2 cycles during chemotherapy.
Measured: At baseline, before and after radiation therapy, and every 2 cycles during chemotherapy
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Jan 2006 (estimated)
- Study startMay 2005
- Primary completionMay 2021 (estimated)
- Study completionMay 2021 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Brain and Central Nervous System TumorsStudies of the same condition, open and under way.
- More trials run by Northwestern UniversityThe 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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 50 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Northwestern University
- Sponsor type
- University, hospital or other
- Collaborators
- Cephalon, CTI BioPharma
- Responsible party
- Sponsor
- Investigators
- Jeffrey Raizer, MD, Principal investigator, Northwestern University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00275067
- Sponsor's protocol ID
- NU 04C1
- Other IDs
- NU 04C1, CDR0000456504, STU00007792
- Status last verified
- Feb 2020
- First submitted
- 10 Jan 2006
- Last updated
- 25 Feb 2020
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 25 Feb 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I/II Trial of Arsenic Trioxide and Temozolomide in Combination With Radiation Therapy for Patients With Malignant Gliomas
- ClinicalTrials.gov ID
- NCT00275067
- Acronym / sponsor ID
- NU 04C1
- Conditions
- Brain and Central Nervous System Tumors
- Keywords
- adult anaplastic astrocytoma, adult gliosarcoma, adult anaplastic oligodendroglioma, adult mixed glioma, adult glioblastoma, adult giant cell glioblastoma, recurrent adult brain tumor
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 50 participants (estimated)
- Lead sponsor
- Northwestern UniversityUniversity, hospital or other
- Collaborators
- Cephalon, CTI BioPharma
- Study start
- May 2005
- Primary completion
- May 2021 (estimated)
- Study completion
- May 2021 (estimated)
- First posted
- 11 Jan 2006 (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.
RATIONALE: Drugs used in chemotherapy, such as arsenic trioxide and temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving arsenic trioxide and temozolomide together with radiation therapy after surgery may kill any remaining tumor cells.
PURPOSE: This phase I/II trial is studying the side effects and best dose of arsenic trioxide and temozolomide when given together with radiation therapy and to see how well they work in treating patients with malignant glioma that has been removed by surgery.
Detailed description
OBJECTIVES:
Primary
- Determine the maximum tolerated dose (MTD) of arsenic trioxide and temozolomide when combined with radiotherapy in patients with resected supratentorial malignant glioma. (Phase I)
- Determine the toxicity of this regimen in these patients. (Phase I)
Secondary
- Determine the 6- and 12-month progression-free survival of patients treated with this regimen once an MTD is reached. (Phase II)
- Determine the radiographic response for patients treated with the above regimen. (Phase II)
- Determine the safety of this regimen in these patients. (Phase II)
OUTLINE: This is a phase I, dose-escalation study of arsenic trioxide and temozolomide followed by a phase II study.
- Phase I: Patients undergo radiotherapy once daily 5 days a week and receive oral temozolomide once daily for approximately 6½ weeks. Patients also receive arsenic trioxide IV over 1-4 hours once daily, 5 days a week in week 1 and then twice a week in weeks 2-7. Beginning within 3-5 weeks after completion of radiotherapy, patients receive oral temozolomide once daily on days 1-5. Treatment with temozolomide repeats every 28 days for up to 1 year in the absence of disease progression and unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of arsenic trioxide and temozolomide until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 1 of 3 or 2 of 6 patients experience dose-limiting toxicity.
- Phase II: Patients undergo radiotherapy and receive arsenic trioxide and temozolomide as in phase I at the MTD. Patients then receive temozolomide as in phase I for up to 1 year in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed periodically for 1 year.
PROJECTED ACCRUAL: A total of 12-18 patients will be accrued for the phase I portion of this study. A total of 25 patients will be accrued for the phase II portion of this study.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Radiation + temozolomide and arsenic trioxide | Experimental | Drug: arsenic trioxide, Drug: temozolomide, Radiation: radiation therapyRadiation therapy followed by the combination of temozolomide and arsenic trioxide at the maximum tolerated dose determined in phase 1 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
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 |
|---|---|---|
| arsenic trioxideAlso: ATO, TRISENOXArsenic trioxide administered intravenously at a dose of 0.20mg/kg Daily x 5 week then twice per week | Drug | Radiation + temozolomide and arsenic trioxide |
| temozolomideAlso: TMZ, TemodarTemozolomide administered orally once per day 1 hour prior to radiation therapy at a dose of 75 mg/m2 x 42 days; at a dose of 200mg/m2 for 5 days every cycle (1 cycle = 28 days) after radiation therapy | Drug | Radiation + temozolomide and arsenic trioxide |
| radiation therapyAll patients will receive 5940-6120 cGy of radiation therapy as 28-33 treatments/fractions (180-200 cGy/treatment) depending on whether they receive standard 3-D conformal radiation therapy or intensity modulated radiation therapy. | Radiation | Radiation + temozolomide and arsenic trioxide |
Primary outcome
Maximum tolerated dose of arsenic trioxide and temozolomide in combination with radiotherapy
Time frame: Toxicity evaluated prior to each treatment cycle
Escalating doses of study drug until dose limiting toxicities are observed.
Collect data on the toxicity of arsenic and temozolomide during radiation therapy
Time frame: Toxicity evaluated prior to each treatment cycle
Toxicity of this drug combination during radiation therapy will be assessed.
Assess serum biomarkers and correlate with tumor tissue
Time frame: At baseline, during radiation therapy, and prior to each cycle of chemotherapy
Blood will be drawn at baseline, during radiation therapy, and prior to each cycle of chemotherapy to assess serum biomarkers and correlate with tumor tissue.
6 secondary outcomes
Determine progression free survival at 6 and 12 months
Time frame: At 6 and 12 months after beginning chemotherapy
Determine time to disease progression
Time frame: At 6 and 12 months after beginning chemotherapy
To determine overall survival
Time frame: Every 6 months while on treatment
To determine radiographic response to study regimen
Time frame: Every 6 months while on treatment
To collect safety data during the radiation therapy phase
Time frame: Weekly during radiation therapy
To evaluate a potential surrogate marker for outcomes
Time frame: At baseline, before and after radiation therapy, and every 2 cycles during chemotherapy
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Feb 2020.
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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.
Jeffrey Raizer, MD principal investigator
Northwestern University
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing arsenic trioxide, temozolomide and radiation therapy in people with Brain and Central Nervous System Tumors, run by Northwestern University 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?
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 25 Feb 2020. 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 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 of arsenic trioxide and temozolomide in combination with radiotherapy (time frame: Toxicity evaluated prior to each treatment cycle). The study lists 3 primary outcomes in all. 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 25 Feb 2020.