A Phase 2 interventional study of O6-benzylguanine and temozolomide in Brain and Central Nervous System Tumors, sponsored by National Cancer Institute (NCI). Terminated at 2 sites in United States. Open to participants aged 18 Years to 120 Years. Per ClinicalTrials.gov, last updated 2017-03-28.
Sponsored by National Cancer Institute (NCI) · Phase 2, Interventional, and Treatment
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.
1,920 studies on the registry are indexed under Glioblastoma; 450 are open to participants now.
This study's enrollment of 12 is below the median of 36 across 1,618 interventional studies indexed under Glioblastoma.
Browse Glioblastoma studies →National Cancer Institute (NCI) is the lead sponsor of 3,506 studies on the registry; 334 are open to participants now.
Of its 402 completed or terminated interventional studies of FDA-regulated products, 365 (91%) have results posted.
Counted across the registry records on this site, refreshed daily.
DISEASE CHARACTERISTICS:
Histologically confirmed glioblastoma multiforme (GBM), including the following:
Temozolomide-resistant disease, as defined by the following:
Must have failed prior radiotherapy
PATIENT CHARACTERISTICS:
PRIOR CONCURRENT THERAPY:
Prior resection of recurrent or progressive tumor allowed if all the following criteria are met:
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.
Drug: O6-benzylguanine · Drug: temozolomide
Also known as: 06-BG
Also known as: Temodar
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.
Time frame: 2-4 weeks
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).
Time frame: 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.
Time frame: 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
Time frame: 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
Time frame: up to 2 years
Overall Survival
Defined as the interval between the day of first administration of treatment and the date of death.
Time frame: up to 2 years
| Milestone | O6-benzylguanine & Temozolomide in Glioblastoma |
|---|---|
| Started | 12 |
| Completed | 0 |
| Not completed | 12 |
| Withdrew: Progression | 4 |
| Withdrew: Adverse event | 2 |
| Withdrew: Death | 6 |
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 measurements were reported for this outcome.
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).
No measurements were reported for this outcome.
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.
| Participants | O6-benzylguanine & Temozolomide in Glioblastoma |
|---|---|
| Toxicity as Assessed by the Common Terminology Criteria in Adverse Events (CTCAE v 3) | 12 |
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 measurements were reported for this outcome.
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 measurements were reported for this outcome.
Defined as the interval between the day of first administration of treatment and the date of death.
No measurements were reported for this outcome.
Collected over 18 months and 4 days. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| O6-benzylguanine & Temozolomide in Glioblastoma | 6/12 (50%) | 8/12 (66.7%) | 9/12 (75%) |
| Event | O6-benzylguanine & Temozolomide in Glioblastoma |
|---|---|
| Death due to progressive diseaseGeneral disorders | 6/12 |
| Leukocytes (total WBC)Blood and lymphatic system disorders | 4/12 |
| SeizureNervous system disorders | 4/12 |
| PlateletsBlood and lymphatic system disorders | 3/12 |
| ALT, SGPT (serum glutamic pyruvic transaminase)Metabolism and nutrition disorders | 2/12 |
| LymphopeniaBlood and lymphatic system disorders | 2/12 |
| Neutrophils/granulocytes (ANC/AGC)Blood and lymphatic system disorders | 2/12 |
| AST, SGOT(serum glutamic oxaloacetic transaminase)Metabolism and nutrition disorders | 1/12 |
| HypothermiaGeneral disorders | 1/12 |
| Muscle weakness, generalized or specific area (not due to neuropathy)::Left-sidedMusculoskeletal and connective tissue disorders | 1/12 |
| Event | O6-benzylguanine & Temozolomide in Glioblastoma |
|---|---|
| Leukocytes (total WBC)Blood and lymphatic system disorders | 5/12 |
| Neutrophils/granulocytes (ANC/AGC)Blood and lymphatic system disorders | 5/12 |
| LymphopeniaBlood and lymphatic system disorders | 4/12 |
| PlateletsBlood and lymphatic system disorders | 4/12 |
| ALT, SGPT (serum glutamic pyruvic transaminase)Metabolism and nutrition disorders | 3/12 |
| AST, SGOT(serum glutamic oxaloacetic transaminase)Metabolism and nutrition disorders | 2/12 |
| Cushingoid appearance (e.g., moon face, buffalo hump, centripetal obesity, cutaneous striae)Endocrine disorders | 2/12 |
| Bilirubin (hyperbilirubinemia)Metabolism and nutrition disorders | 1/12 |
| Blood/Bone Marrow - Other (Specify, leukopenia)Blood and lymphatic system disorders | 1/12 |
| ConfusionNervous system disorders | 1/12 |
| Age, Categorical(Participants) | O6-benzylguanine & Temozolomide in Glioblastoma |
|---|---|
| <=18 years | 0 |
| Between 18 and 65 years | 10 |
| >=65 years | 2 |
| Age, Continuous(years) | O6-benzylguanine & Temozolomide in Glioblastoma |
|---|---|
| Mean | 52.03 ± 9.64 |
| Sex: Female, Male(Participants) | O6-benzylguanine & Temozolomide in Glioblastoma |
|---|---|
| Female | 1 |
| Male | 11 |
| Ethnicity (NIH/OMB)(Participants) | O6-benzylguanine & Temozolomide in Glioblastoma |
|---|---|
| Hispanic or Latino | 0 |
| Not Hispanic or Latino | 10 |
| Unknown or Not Reported | 2 |
| Race (NIH/OMB)(Participants) | O6-benzylguanine & Temozolomide in Glioblastoma |
|---|---|
| American Indian or Alaska Native | 0 |
| Asian | 1 |
| Native Hawaiian or Other Pacific Islander | 0 |
| Black or African American | 2 |
| White | 9 |
| More than one race | 0 |
| Unknown or Not Reported | 0 |
| Region of Enrollment(Participants) | O6-benzylguanine & Temozolomide in Glioblastoma |
|---|---|
| United States | 12 |
Plan to share: No
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