Trial Outcomes & Findings for Gossypol in Treating Patients With Progressive or Recurrent Glioblastoma Multiforme (NCT NCT00540722)
NCT ID: NCT00540722
Last Updated: 2017-08-11
Results Overview
The overall failure rate will be estimated along with 95% confidence intervals. A median time of survival will be estimated using standard methods.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
56 participants
Primary outcome timeframe
4.5 years
Results posted on
2017-08-11
Participant Flow
Patients were enrolled on this study from Jan 2008 through September 2008. Patients were enrolled in an outpatient setting at 9 oncology clinical sites
Participant milestones
| Measure |
Treatment (R-(-)-Gossypol Acetic Acid)
Patients receive oral R-(-)-gossypol once daily on days 1-21. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.
Laboratory Biomarker Analysis: Patients undergo tumor tissue and blood sample collection at baseline and periodically during study for biomarker correlative studies. Archived tumor tissue samples, if available, are analyzed for Bcl-2 family protein expression (e.g., Bcl-2, Bcl-xL, MCl-1, Bax, Bak, and BH3 domain for BH3 members only) and o6-methylguanine-DNA-methyltransferase (MGMT) gene methylation status. Blood samples are analyzed for apoptotic protein levels (Bcl-2) by enzyme-linked immunosorbent assay.
R-(-)-gossypol acetic acid: Given PO
laboratory biomarker analysis: Correlative studies
|
|---|---|
|
Overall Study
STARTED
|
56
|
|
Overall Study
COMPLETED
|
56
|
|
Overall Study
NOT COMPLETED
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Gossypol in Treating Patients With Progressive or Recurrent Glioblastoma Multiforme
Baseline characteristics by cohort
| Measure |
Treatment (R-(-)-Gossypol Acetic Acid)
n=56 Participants
Patients receive oral R-(-)-gossypol once daily on days 1-21. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.
Laboratory Biomarker Analysis: Patients undergo tumor tissue and blood sample collection at baseline and periodically during study for biomarker correlative studies. Archived tumor tissue samples, if available, are analyzed for Bcl-2 family protein expression (e.g., Bcl-2, Bcl-xL, MCl-1, Bax, Bak, and BH3 domain for BH3 members only) and MGMT gene methylation status. Blood samples are analyzed for apoptotic protein levels (Bcl-2) by enzyme-linked immunosorbent assay.
R-(-)-gossypol acetic acid: Given PO
laboratory biomarker analysis: Correlative studies
|
|---|---|
|
Age, Continuous
|
59 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
25 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
31 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 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
|
3 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
53 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
|
|
Karnofsky Performance Status (KPS)
|
80 units on a scale
n=5 Participants
|
|
Histology
Glioblastoma
|
54 Participants
n=5 Participants
|
|
Histology
Gliosarcoma
|
2 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 4.5 yearsThe overall failure rate will be estimated along with 95% confidence intervals. A median time of survival will be estimated using standard methods.
Outcome measures
| Measure |
Treatment (R-(-)-Gossypol Acetic Acid)
n=56 Participants
Patients receive oral R-(-)-gossypol once daily on days 1-21. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.
Laboratory Biomarker Analysis: Patients undergo tumor tissue and blood sample collection at baseline and periodically during study for biomarker correlative studies. Archived tumor tissue samples, if available, are analyzed for Bcl-2 family protein expression (e.g., Bcl-2, Bcl-xL, MCl-1, Bax, Bak, and BH3 domain for BH3 members only) and o6-methylguanine-DNA-methyltransferase (MGMT) gene methylation status. Blood samples are analyzed for apoptotic protein levels (Bcl-2) by enzyme-linked immunosorbent assay.
R-(-)-gossypol acetic acid: Given PO
laboratory biomarker analysis: Correlative studies
|
|---|---|
|
Overall Survival
|
5.9 months
Interval 3.9 to 7.3
|
SECONDARY outcome
Timeframe: 3 yearsThe proportion of patients with serious or life threatening (grade 3 and 4) toxicities will be estimated using NCI CTCAE
Outcome measures
| Measure |
Treatment (R-(-)-Gossypol Acetic Acid)
n=56 Participants
Patients receive oral R-(-)-gossypol once daily on days 1-21. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.
Laboratory Biomarker Analysis: Patients undergo tumor tissue and blood sample collection at baseline and periodically during study for biomarker correlative studies. Archived tumor tissue samples, if available, are analyzed for Bcl-2 family protein expression (e.g., Bcl-2, Bcl-xL, MCl-1, Bax, Bak, and BH3 domain for BH3 members only) and o6-methylguanine-DNA-methyltransferase (MGMT) gene methylation status. Blood samples are analyzed for apoptotic protein levels (Bcl-2) by enzyme-linked immunosorbent assay.
R-(-)-gossypol acetic acid: Given PO
laboratory biomarker analysis: Correlative studies
|
|---|---|
|
Percent of Patients With Grade 3 and 4 Adverse Events Related to Treatment
Seizure
|
2 percentage of participants
|
|
Percent of Patients With Grade 3 and 4 Adverse Events Related to Treatment
IIeus
|
2 percentage of participants
|
|
Percent of Patients With Grade 3 and 4 Adverse Events Related to Treatment
Hypophosphatemia
|
2 percentage of participants
|
|
Percent of Patients With Grade 3 and 4 Adverse Events Related to Treatment
fatigue
|
4 percentage of participants
|
|
Percent of Patients With Grade 3 and 4 Adverse Events Related to Treatment
Elevated troponin
|
2 percentage of participants
|
SECONDARY outcome
Timeframe: 3 yearsPopulation: 5 patients were not evaluable for response
Complete response Complete disappearance of all tumor on MRI scan, off all glucocorticoids with stable or improving neurological exam minimum of 4 wks Partial response Greater than or equal 50% reduction in tumor size on MRI, on sable or decreasing glucocorticoids with stable or improving neurological exam for a minimum of 4 wks. Progressive disease Progressive neurological abnormalities not explained by other causes or greater than 25% increase in size of tumor or if new lesion. Stable disease Clinical status and MRI does not qualify for complete response, partial response or progression
Outcome measures
| Measure |
Treatment (R-(-)-Gossypol Acetic Acid)
n=56 Participants
Patients receive oral R-(-)-gossypol once daily on days 1-21. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.
Laboratory Biomarker Analysis: Patients undergo tumor tissue and blood sample collection at baseline and periodically during study for biomarker correlative studies. Archived tumor tissue samples, if available, are analyzed for Bcl-2 family protein expression (e.g., Bcl-2, Bcl-xL, MCl-1, Bax, Bak, and BH3 domain for BH3 members only) and o6-methylguanine-DNA-methyltransferase (MGMT) gene methylation status. Blood samples are analyzed for apoptotic protein levels (Bcl-2) by enzyme-linked immunosorbent assay.
R-(-)-gossypol acetic acid: Given PO
laboratory biomarker analysis: Correlative studies
|
|---|---|
|
Tumor Response Rate
Complete Response
|
0 Participants
|
|
Tumor Response Rate
Partial Response
|
1 Participants
|
|
Tumor Response Rate
Stable Disease
|
15 Participants
|
|
Tumor Response Rate
Progression
|
35 Participants
|
|
Tumor Response Rate
not evaluable
|
5 Participants
|
SECONDARY outcome
Timeframe: 6 monthsThe probability of 6-month progression-free survival will be estimated using binomial distribution.
Outcome measures
| Measure |
Treatment (R-(-)-Gossypol Acetic Acid)
n=56 Participants
Patients receive oral R-(-)-gossypol once daily on days 1-21. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.
Laboratory Biomarker Analysis: Patients undergo tumor tissue and blood sample collection at baseline and periodically during study for biomarker correlative studies. Archived tumor tissue samples, if available, are analyzed for Bcl-2 family protein expression (e.g., Bcl-2, Bcl-xL, MCl-1, Bax, Bak, and BH3 domain for BH3 members only) and o6-methylguanine-DNA-methyltransferase (MGMT) gene methylation status. Blood samples are analyzed for apoptotic protein levels (Bcl-2) by enzyme-linked immunosorbent assay.
R-(-)-gossypol acetic acid: Given PO
laboratory biomarker analysis: Correlative studies
|
|---|---|
|
Progression-free Survival Rate, Defined as Patient Who is Alive and Disease Progression Free at the Time of 26-week (6 Months) From First Day of the Treatment
|
1.87 months
Interval 1.87 to 2.17
|
OTHER_PRE_SPECIFIED outcome
Timeframe: 1 monthPopulation: no data to report. Not enough archived tumor tissue and survival outcome did not warrant an analysis of the Pharmacokinetics (PK)
Archived tumor tissue and 1 serum sample pre first dose and 1 sample anytime during week 2 of cycle 1
Outcome measures
Outcome data not reported
Adverse Events
Treatment (R-(-)-Gossypol Acetic Acid)
Serious events: 6 serious events
Other events: 28 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Treatment (R-(-)-Gossypol Acetic Acid)
n=56 participants at risk
Patients receive oral R-(-)-gossypol once daily on days 1-21. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.
Laboratory Biomarker Analysis: Patients undergo tumor tissue and blood sample collection at baseline and periodically during study for biomarker correlative studies. Archived tumor tissue samples, if available, are analyzed for Bcl-2 family protein expression (e.g., Bcl-2, Bcl-xL, MCl-1, Bax, Bak, and BH3 domain for BH3 members only) and MGMT gene methylation status. Blood samples are analyzed for apoptotic protein levels (Bcl-2) by enzyme-linked immunosorbent assay.
R-(-)-gossypol acetic acid: Given PO
laboratory biomarker analysis: Correlative studies
|
|---|---|
|
Nervous system disorders
Seizure
|
1.8%
1/56 • Number of events 1 • start of first dose until at least 30 days post last dose. approximately 3 years
|
|
Gastrointestinal disorders
lleus
|
1.8%
1/56 • Number of events 1 • start of first dose until at least 30 days post last dose. approximately 3 years
|
|
Metabolism and nutrition disorders
hypophosphatemia
|
1.8%
1/56 • Number of events 1 • start of first dose until at least 30 days post last dose. approximately 3 years
|
|
General disorders
fatigue
|
3.6%
2/56 • Number of events 2 • start of first dose until at least 30 days post last dose. approximately 3 years
|
|
Cardiac disorders
cardiac disorder other
|
1.8%
1/56 • Number of events 1 • start of first dose until at least 30 days post last dose. approximately 3 years
|
Other adverse events
| Measure |
Treatment (R-(-)-Gossypol Acetic Acid)
n=56 participants at risk
Patients receive oral R-(-)-gossypol once daily on days 1-21. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.
Laboratory Biomarker Analysis: Patients undergo tumor tissue and blood sample collection at baseline and periodically during study for biomarker correlative studies. Archived tumor tissue samples, if available, are analyzed for Bcl-2 family protein expression (e.g., Bcl-2, Bcl-xL, MCl-1, Bax, Bak, and BH3 domain for BH3 members only) and MGMT gene methylation status. Blood samples are analyzed for apoptotic protein levels (Bcl-2) by enzyme-linked immunosorbent assay.
R-(-)-gossypol acetic acid: Given PO
laboratory biomarker analysis: Correlative studies
|
|---|---|
|
Gastrointestinal disorders
vomiting
|
7.1%
4/56 • Number of events 4 • start of first dose until at least 30 days post last dose. approximately 3 years
|
|
Skin and subcutaneous tissue disorders
Rash maculo-papular
|
7.1%
4/56 • Number of events 4 • start of first dose until at least 30 days post last dose. approximately 3 years
|
|
Nervous system disorders
peripheral sensory neuropathy
|
7.1%
4/56 • Number of events 4 • start of first dose until at least 30 days post last dose. approximately 3 years
|
|
General disorders
fatigue
|
37.5%
21/56 • Number of events 21 • start of first dose until at least 30 days post last dose. approximately 3 years
|
|
Gastrointestinal disorders
diarrhea
|
5.4%
3/56 • Number of events 3 • start of first dose until at least 30 days post last dose. approximately 3 years
|
|
Gastrointestinal disorders
constipation
|
7.1%
4/56 • Number of events 4 • start of first dose until at least 30 days post last dose. approximately 3 years
|
|
Metabolism and nutrition disorders
anorexia
|
5.4%
3/56 • Number of events 3 • start of first dose until at least 30 days post last dose. approximately 3 years
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: LTE60