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| ID | Type | Description | Link |
|---|---|---|---|
| NCI-07-C-0052 | |||
| AOI-NCI-07-C-0052 | |||
| CDR0000529875 | Other Identifier | nci |
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Study closed to accrual after the company chose to stop development of the drug.
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RATIONALE: Drugs used in chemotherapy, such as O(6)-benzylguanine and temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells.
PURPOSE: This phase II trial is studying the side effects and how well giving O(6)-benzylguanine together with temozolomide works in treating patients with glioblastoma multiforme that did not respond to previous temozolomide and radiation therapy.
OBJECTIVES:
OUTLINE: Patients receive O6-benzylguanine intravenous (IV) over 1 hour and oral temozolomide once daily on days 1-5. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed periodically for at least 6 months.
PROJECTED ACCRUAL: A total of 100 patients will be accrued for this study.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| O6-benzylguanine & Temozolomide in Glioblastoma | Experimental | Patients receive O6-benzylguanine intravenous over 1 hour and oral temozolomide once daily on days 1-5. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| O6-benzylguanine | Drug |
|
| |
| Measure | Description | Time Frame |
|---|---|---|
| Confirmed Best Objective Tumor Response Rate (Complete or Partial Response) in Patients With Methylguanine Methyltransferase (MGMT)-Positive Tumors as Assessed by Immunohistochemistry (IHC) | The date of response will be the date the response is first radiographically documented following initiation of therapy (typically, the date of the actual imaging modality). Complete response is complete disappearance of all measurable and evaluable disease. No new lesions. No evidence of non-evaluable disease. Partial response is greater than or equal to a 50% decrease compared to baseline in the sum of products of perpendicular diameters of all measurable lesions. | 2-4 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Objective Tumor Response Rate in Patients With Methylguanine Methyltransferase (MGMT)-Negative Tumors as Assessed by Immunohistochemistry (IHC) | The date of response will be the date the response is first radiographically documented following initiation of therapy (typically, the date of the actual imaging modality). Complete response is complete disappearance of all measurable and evaluable disease. No new lesions. No evidence of non-evaluable disease. Partial response is greater than or equal to a 50% decrease compared to baseline in the sum of products of perpendicular diameters of all measurable lesions. Stable/No disease does not qualify for CR, PR, or progression. Progression is a 25% increase in the sum of products of all measurable lesions (or two largest lesions if too numerous) over the smallest sum observed (over baseline if no decrease) using the same techniques as baseline, OR clear worsening of any evaluable disease, OR appearance of any new lesion/site, OR failure to return for evaluation due to death or deteriorating condition (unless clearly unrelated to this cancer). |
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DISEASE CHARACTERISTICS:
Histologically confirmed glioblastoma multiforme (GBM), including the following:
Temozolomide-resistant disease, as defined by the following:
Must have failed prior radiotherapy
Must have paraffin-embedded tissue blocks or ≥ 4 unstained paraffin-embedded microscope slides available from diagnosis
PATIENT CHARACTERISTICS:
PRIOR CONCURRENT THERAPY:
See Disease Characteristics
Recovered from prior temozolomide
Prior resection of recurrent or progressive tumor allowed if all the following criteria are met:
At least 12 weeks since prior radiotherapy
No other prior therapy (i.e., polifeprosan 20 with carmustine implant [Gliadel wafers] or nitrosoureas)
No other concurrent chemotherapy, radiotherapy, immunotherapy, or investigational agents
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| Name | Affiliation | Role |
|---|---|---|
| Howard A Fine, M.D. | NCI - Neuro-Oncology Branch | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office | Bethesda | Maryland | 20892-1182 | United States | ||
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| ID | Title | Description |
|---|---|---|
| FG000 | O6-benzylguanine & Temozolomide in Glioblastoma | Patients receive O6-benzylguanine intravenous over 1 hour and oral temozolomide once daily on days 1-5. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. O6-benzylguanine temozolomide |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| temozolomide |
| Drug |
|
|
| 2-4 weeks |
| Toxicity as Assessed by the Common Terminology Criteria in Adverse Events (CTCAE v 3) | Here is the number of participants with adverse events. For a detailed list of adverse events, see the adverse event module. Adverse events were assessed by the Common Terminology Criteria in Adverse Events (CTCAE)v3. | 18 months and 4 days |
| Best Overall Response | Defined as the best tumor response recorded from the start of treatment until disease progression or withdrawal from the study. Complete response is complete disappearance of all measurable and evaluable disease. No new lesions. No evidence of non-evaluable disease. Partial response is greater than or equal to a 50% decrease compared to baseline in the sum of products of perpendicular diameters of all measurable lesions. Stable/No disease does not qualify for CR, PR, or progression. Progression is a 25% increase in the sum of products of all measurable lesions (or two largest lesions if too numerous) over the smallest sum observed (over baseline if no decrease) using the same techniques as baseline, OR clear worsening of any evaluable disease, OR appearance of any new lesion/site, OR failure to return for evaluation due to death or deteriorating condition (unless clearly unrelated to this cancer | up to 2 years |
| Progression-free Survival | Defined as the interval between the day of first administration of treatment and the first documentation of progressive disease or date of death. Progression is a 25% increase in the sum of products of all measurable lesions (or two largest lesions if too numerous) over the smallest sum observed (over baseline if no decrease) using the same techniques as baseline, OR clear worsening of any evaluable disease, OR appearance of any new lesion/site, OR failure to return for evaluation due to death or deteriorating condition (unless clearly unrelated to this cancer | up to 2 years |
| Overall Survival | Defined as the interval between the day of first administration of treatment and the date of death. | up to 2 years |
| NCI - Neuro-Oncology Branch |
| Bethesda |
| Maryland |
| 20892-8200 |
| United States |
| COMPLETED |
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | O6-benzylguanine & Temozolomide in Glioblastoma | Patients receive O6-benzylguanine intravenous over 1 hour and oral temozolomide once daily on days 1-5. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. O6-benzylguanine temozolomide |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants | Participants | No |
| |||||||||||||||||||
| Age, Continuous | Mean | Standard Deviation | years |
| |||||||||||||||||||
| Sex: Female, Male | Count of Participants | Participants | No |
| |||||||||||||||||||
| Ethnicity (NIH/OMB) | Count of Participants | Participants | No |
| |||||||||||||||||||
| Race (NIH/OMB) | Count of Participants | Participants | No |
| |||||||||||||||||||
| Region of Enrollment | Count of Participants | Participants | No |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Confirmed Best Objective Tumor Response Rate (Complete or Partial Response) in Patients With Methylguanine Methyltransferase (MGMT)-Positive Tumors as Assessed by Immunohistochemistry (IHC) | The date of response will be the date the response is first radiographically documented following initiation of therapy (typically, the date of the actual imaging modality). Complete response is complete disappearance of all measurable and evaluable disease. No new lesions. No evidence of non-evaluable disease. Partial response is greater than or equal to a 50% decrease compared to baseline in the sum of products of perpendicular diameters of all measurable lesions. | No analysis was performed. The study was closed to accrual after the company chose to stop the development of the drug. | Posted | 2-4 weeks |
|
| |||||||||||||||||||
| Secondary | Objective Tumor Response Rate in Patients With Methylguanine Methyltransferase (MGMT)-Negative Tumors as Assessed by Immunohistochemistry (IHC) | The date of response will be the date the response is first radiographically documented following initiation of therapy (typically, the date of the actual imaging modality). Complete response is complete disappearance of all measurable and evaluable disease. No new lesions. No evidence of non-evaluable disease. Partial response is greater than or equal to a 50% decrease compared to baseline in the sum of products of perpendicular diameters of all measurable lesions. Stable/No disease does not qualify for CR, PR, or progression. Progression is a 25% increase in the sum of products of all measurable lesions (or two largest lesions if too numerous) over the smallest sum observed (over baseline if no decrease) using the same techniques as baseline, OR clear worsening of any evaluable disease, OR appearance of any new lesion/site, OR failure to return for evaluation due to death or deteriorating condition (unless clearly unrelated to this cancer). | Twelve patients were enrolled. The principal investigator wished to analyze the data but felt that there was insufficient data to report on and therefore closed the protocol when he left the National Cancer Institute (NCI). | Posted | 2-4 weeks |
| ||||||||||||||||||||
| Secondary | Toxicity as Assessed by the Common Terminology Criteria in Adverse Events (CTCAE v 3) | Here is the number of participants with adverse events. For a detailed list of adverse events, see the adverse event module. Adverse events were assessed by the Common Terminology Criteria in Adverse Events (CTCAE)v3. | Posted | Count of Participants | Participants | No | 18 months and 4 days |
|
| |||||||||||||||||
| Secondary | Best Overall Response | Defined as the best tumor response recorded from the start of treatment until disease progression or withdrawal from the study. Complete response is complete disappearance of all measurable and evaluable disease. No new lesions. No evidence of non-evaluable disease. Partial response is greater than or equal to a 50% decrease compared to baseline in the sum of products of perpendicular diameters of all measurable lesions. Stable/No disease does not qualify for CR, PR, or progression. Progression is a 25% increase in the sum of products of all measurable lesions (or two largest lesions if too numerous) over the smallest sum observed (over baseline if no decrease) using the same techniques as baseline, OR clear worsening of any evaluable disease, OR appearance of any new lesion/site, OR failure to return for evaluation due to death or deteriorating condition (unless clearly unrelated to this cancer | No analysis was performed. The study was closed to accrual after the company chose to stop the development of the drug. | Posted | up to 2 years |
|
| |||||||||||||||||||
| Secondary | Progression-free Survival | Defined as the interval between the day of first administration of treatment and the first documentation of progressive disease or date of death. Progression is a 25% increase in the sum of products of all measurable lesions (or two largest lesions if too numerous) over the smallest sum observed (over baseline if no decrease) using the same techniques as baseline, OR clear worsening of any evaluable disease, OR appearance of any new lesion/site, OR failure to return for evaluation due to death or deteriorating condition (unless clearly unrelated to this cancer | No analysis was performed. The study was closed to accrual after the company chose to stop the development of the drug. | Posted | up to 2 years |
|
| |||||||||||||||||||
| Secondary | Overall Survival | Defined as the interval between the day of first administration of treatment and the date of death. | No analysis was performed. The study was closed to accrual after the company chose to stop the development of the drug. | Posted | up to 2 years |
|
|
18 months and 4 days
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | O6-benzylguanine & Temozolomide in Glioblastoma | Patients receive O6-benzylguanine intravenous over 1 hour and oral temozolomide once daily on days 1-5. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. O6-benzylguanine temozolomide | 6 | 12 | 8 | 12 | 9 | 12 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| ALT, SGPT (serum glutamic pyruvic transaminase) | Metabolism and nutrition disorders | CTCAE (3.0) | Systematic Assessment |
| |
| AST, SGOT(serum glutamic oxaloacetic transaminase) | Metabolism and nutrition disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Hypothermia | General disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Leukocytes (total WBC) | Blood and lymphatic system disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Lymphopenia | Blood and lymphatic system disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Muscle weakness, generalized or specific area (not due to neuropathy)::Left-sided | Musculoskeletal and connective tissue disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Neutrophils/granulocytes (ANC/AGC) | Blood and lymphatic system disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Platelets | Blood and lymphatic system disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Potassium, serum-high (hyperkalemia) | Metabolism and nutrition disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Seizure | Nervous system disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Thrombosis/thrombus/embolism | Vascular disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Death due to progressive disease | General disorders | CTCAE (3.0) | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| ALT, SGPT (serum glutamic pyruvic transaminase) | Metabolism and nutrition disorders | CTCAE (3.0) | Systematic Assessment |
| |
| AST, SGOT(serum glutamic oxaloacetic transaminase) | Metabolism and nutrition disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Bilirubin (hyperbilirubinemia) | Metabolism and nutrition disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Blood/Bone Marrow - Other (Specify, leukopenia) | Blood and lymphatic system disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Confusion | Nervous system disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Cushingoid appearance (e.g., moon face, buffalo hump, centripetal obesity, cutaneous striae) | Endocrine disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Edema: limb | Blood and lymphatic system disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Hair loss/alopecia (scalp or body) | Skin and subcutaneous tissue disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Hemoglobin | Blood and lymphatic system disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Leukocytes (total WBC) | Blood and lymphatic system disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Lymphopenia | Blood and lymphatic system disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Magnesium, serum-high (hypermagnesemia) | Metabolism and nutrition disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Mucositis/stomatitis (clinical exam)::Oral cavity | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Neutrophils/granulocytes (ANC/AGC) | Blood and lymphatic system disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Platelets | Blood and lymphatic system disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Sodium, serum-high (hypernatremia) | Metabolism and nutrition disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
|
Dr. Howard A. Fine is no longer with the National Cancer Institute (NCI). For historical reasons, he is listed as the (original principal investigator) study official for this study.
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Mark Gilbert | National Cancer Institute | 301-402-6383 | gilbertmr@mail.nih.gov |
| ID | Term |
|---|---|
| D016543 | Central Nervous System Neoplasms |
| D005909 | Glioblastoma |
| D018316 | Gliosarcoma |
| D001932 | Brain Neoplasms |
| ID | Term |
|---|---|
| D009423 | Nervous System Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D009422 | Nervous System Diseases |
| D001254 | Astrocytoma |
| D005910 | Glioma |
| D018302 | Neoplasms, Neuroepithelial |
| D017599 | Neuroectodermal Tumors |
| D009373 | Neoplasms, Germ Cell and Embryonal |
| D009370 | Neoplasms by Histologic Type |
| D009375 | Neoplasms, Glandular and Epithelial |
| D009380 | Neoplasms, Nerve Tissue |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
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| ID | Term |
|---|---|
| C064976 | O(6)-benzylguanine |
| D000077204 | Temozolomide |
| ID | Term |
|---|---|
| D003606 | Dacarbazine |
| D014226 | Triazenes |
| D009930 | Organic Chemicals |
| D007093 | Imidazoles |
| D001393 | Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
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| Unknown or Not Reported |
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| Native Hawaiian or Other Pacific Islander |
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| Black or African American |
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| White |
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| More than one race |
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| Unknown or Not Reported |
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| Units | Counts |
|---|---|
| Participants |
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| Participants |
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