Trial Outcomes & Findings for O(6)-Benzylguanine and Temozolomide in Treating Patients With Glioblastoma Multiforme That Did Not Respond to Previous Temozolomide and Radiation Therapy (NCT NCT00436436)

NCT ID: NCT00436436

Last Updated: 2017-03-28

Results Overview

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.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

12 participants

Primary outcome timeframe

2-4 weeks

Results posted on

2017-03-28

Participant Flow

Participant milestones

Participant milestones
Measure
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
Overall Study
STARTED
12
Overall Study
COMPLETED
0
Overall Study
NOT COMPLETED
12

Reasons for withdrawal

Reasons for withdrawal
Measure
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
Overall Study
Progression
4
Overall Study
Adverse Event
2
Overall Study
Death
6

Baseline Characteristics

O(6)-Benzylguanine and Temozolomide in Treating Patients With Glioblastoma Multiforme That Did Not Respond to Previous Temozolomide and Radiation Therapy

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
O6-benzylguanine & Temozolomide in Glioblastoma
n=12 Participants
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
Age, Categorical
<=18 years
0 Participants
n=5 Participants
Age, Categorical
Between 18 and 65 years
10 Participants
n=5 Participants
Age, Categorical
>=65 years
2 Participants
n=5 Participants
Age, Continuous
52.03 years
STANDARD_DEVIATION 9.64 • n=5 Participants
Sex: Female, Male
Female
1 Participants
n=5 Participants
Sex: Female, Male
Male
11 Participants
n=5 Participants
Ethnicity (NIH/OMB)
Hispanic or Latino
0 Participants
n=5 Participants
Ethnicity (NIH/OMB)
Not Hispanic or Latino
10 Participants
n=5 Participants
Ethnicity (NIH/OMB)
Unknown or Not Reported
2 Participants
n=5 Participants
Race (NIH/OMB)
American Indian or Alaska Native
0 Participants
n=5 Participants
Race (NIH/OMB)
Asian
1 Participants
n=5 Participants
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
0 Participants
n=5 Participants
Race (NIH/OMB)
Black or African American
2 Participants
n=5 Participants
Race (NIH/OMB)
White
9 Participants
n=5 Participants
Race (NIH/OMB)
More than one race
0 Participants
n=5 Participants
Race (NIH/OMB)
Unknown or Not Reported
0 Participants
n=5 Participants
Region of Enrollment
United States
12 Participants
n=5 Participants

PRIMARY outcome

Timeframe: 2-4 weeks

Population: No analysis was performed. The study was closed to accrual after the company chose to stop the development of the drug.

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 2-4 weeks

Population: 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).

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).

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 18 months and 4 days

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.

Outcome measures

Outcome measures
Measure
O6-benzylguanine & Temozolomide in Glioblastoma
n=12 Participants
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
Toxicity as Assessed by the Common Terminology Criteria in Adverse Events (CTCAE v 3)
12 Participants

SECONDARY outcome

Timeframe: up to 2 years

Population: No analysis was performed. The study was closed to accrual after the company chose to stop the development of the drug.

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

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: up to 2 years

Population: No analysis was performed. The study was closed to accrual after the company chose to stop the development of the drug.

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

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: up to 2 years

Population: No analysis was performed. The study was closed to accrual after the company chose to stop the development of the drug.

Defined as the interval between the day of first administration of treatment and the date of death.

Outcome measures

Outcome data not reported

Adverse Events

O6-benzylguanine & Temozolomide in Glioblastoma

Serious events: 8 serious events
Other events: 9 other events
Deaths: 6 deaths

Serious adverse events

Serious adverse events
Measure
O6-benzylguanine & Temozolomide in Glioblastoma
n=12 participants at risk
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
Metabolism and nutrition disorders
ALT, SGPT (serum glutamic pyruvic transaminase)
16.7%
2/12 • Number of events 3 • 18 months and 4 days
Metabolism and nutrition disorders
AST, SGOT(serum glutamic oxaloacetic transaminase)
8.3%
1/12 • Number of events 1 • 18 months and 4 days
General disorders
Hypothermia
8.3%
1/12 • Number of events 1 • 18 months and 4 days
Blood and lymphatic system disorders
Leukocytes (total WBC)
33.3%
4/12 • Number of events 6 • 18 months and 4 days
Blood and lymphatic system disorders
Lymphopenia
16.7%
2/12 • Number of events 5 • 18 months and 4 days
Musculoskeletal and connective tissue disorders
Muscle weakness, generalized or specific area (not due to neuropathy)::Left-sided
8.3%
1/12 • Number of events 1 • 18 months and 4 days
Blood and lymphatic system disorders
Neutrophils/granulocytes (ANC/AGC)
16.7%
2/12 • Number of events 3 • 18 months and 4 days
Blood and lymphatic system disorders
Platelets
25.0%
3/12 • Number of events 7 • 18 months and 4 days
Metabolism and nutrition disorders
Potassium, serum-high (hyperkalemia)
8.3%
1/12 • Number of events 1 • 18 months and 4 days
Nervous system disorders
Seizure
33.3%
4/12 • Number of events 6 • 18 months and 4 days
Vascular disorders
Thrombosis/thrombus/embolism
8.3%
1/12 • Number of events 1 • 18 months and 4 days
General disorders
Death due to progressive disease
50.0%
6/12 • Number of events 6 • 18 months and 4 days

Other adverse events

Other adverse events
Measure
O6-benzylguanine & Temozolomide in Glioblastoma
n=12 participants at risk
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
Metabolism and nutrition disorders
ALT, SGPT (serum glutamic pyruvic transaminase)
25.0%
3/12 • Number of events 4 • 18 months and 4 days
Metabolism and nutrition disorders
AST, SGOT(serum glutamic oxaloacetic transaminase)
16.7%
2/12 • Number of events 2 • 18 months and 4 days
Metabolism and nutrition disorders
Bilirubin (hyperbilirubinemia)
8.3%
1/12 • Number of events 1 • 18 months and 4 days
Blood and lymphatic system disorders
Blood/Bone Marrow - Other (Specify, leukopenia)
8.3%
1/12 • Number of events 1 • 18 months and 4 days
Nervous system disorders
Confusion
8.3%
1/12 • Number of events 1 • 18 months and 4 days
Endocrine disorders
Cushingoid appearance (e.g., moon face, buffalo hump, centripetal obesity, cutaneous striae)
16.7%
2/12 • Number of events 2 • 18 months and 4 days
Blood and lymphatic system disorders
Edema: limb
8.3%
1/12 • Number of events 1 • 18 months and 4 days
Skin and subcutaneous tissue disorders
Hair loss/alopecia (scalp or body)
8.3%
1/12 • Number of events 1 • 18 months and 4 days
Blood and lymphatic system disorders
Hemoglobin
8.3%
1/12 • Number of events 1 • 18 months and 4 days
Blood and lymphatic system disorders
Leukocytes (total WBC)
41.7%
5/12 • Number of events 7 • 18 months and 4 days
Blood and lymphatic system disorders
Lymphopenia
33.3%
4/12 • Number of events 5 • 18 months and 4 days
Metabolism and nutrition disorders
Magnesium, serum-high (hypermagnesemia)
8.3%
1/12 • Number of events 1 • 18 months and 4 days
Gastrointestinal disorders
Mucositis/stomatitis (clinical exam)::Oral cavity
8.3%
1/12 • Number of events 1 • 18 months and 4 days
Blood and lymphatic system disorders
Neutrophils/granulocytes (ANC/AGC)
41.7%
5/12 • Number of events 8 • 18 months and 4 days
Blood and lymphatic system disorders
Platelets
33.3%
4/12 • Number of events 8 • 18 months and 4 days
Metabolism and nutrition disorders
Sodium, serum-high (hypernatremia)
8.3%
1/12 • Number of events 1 • 18 months and 4 days
Gastrointestinal disorders
Vomiting
8.3%
1/12 • Number of events 1 • 18 months and 4 days

Additional Information

Dr. Mark Gilbert

National Cancer Institute

Phone: 301-402-6383

Results disclosure agreements

  • Principal investigator is a sponsor employee
  • Publication restrictions are in place