Adult Giant Cell GlioblastomaPhase 2NCT00540722
Gossypol in Treating Patients With Progressive or Recurrent Glioblastoma Multiforme
A Phase 2 study testing R-(-)-gossypol acetic acid and laboratory biomarker analysis in people with Adult Giant Cell Glioblastoma and Adult Glioblastoma, run by National Cancer Institute (NCI) at 8 sites in United States.
Trial summary
This phase II trial is studying how well gossypol works in treating patients with progressive or recurrent glioblastoma multiforme. Gossypol may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Adult Giant Cell Glioblastoma, Adult Glioblastoma, Adult Gliosarcoma
- What is being tested?
- R-(-)-gossypol acetic acid and laboratory biomarker analysis
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 56 participants
- Where
- 8 sitesUnited States
- Study dates
- Jan 2008to Jun 2012
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
Who may be able to join
- Patients must have histologically confirmed supratentorial glioblastoma multiforme which is progressive or recurrent after radiation therapy ± chemotherapy; patients with previously low grade glioma who progressed after radiotherapy ± chemotherapy and are biopsied and found to have glioblastoma multiforme are eligible
- Patients must have tumor tissue form completed and signed by a pathologist
- Patients must have measurable contrast enhancing progressive or recurrent glioblastoma multiforme by MRI or CT imaging (Within 14 days before starting treatment)
- Patients must have recovered from toxicity of prior therapy; an interval of at least 3 months must have elapsed since the completion of the most recent course of radiation therapy, while at least 3 weeks must have elapsed since the completion of a non-nitrosourea containing chemotherapy regimen, and at least 6 weeks since the completion of a nitrosourea containing chemotherapy regimen; NOTE: For non-cytotoxic, FDA approved agents (i.e. celebrex, thalidomide, etc.) therapy could be started 2 weeks after discontinuing this agent provided the patient has fully recovered from all toxicity associated with the agent; for investigational, non-cytotoxic agents a minimum of 3 weeks must have elapsed before the patient will be eligible for this study
- Patients must have a Karnofsky performance status >= 60% (i.e. the patient must be able to care for himself/herself with occasional help from others)
- Absolute neutrophil count >= 1500/mm^3
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- Platelets >= 100,000/mm^3
- Creatinine =< 1.5mg/dl
- Total Bilirubin =< 1.5mg/dl
- Transaminases =< 2.5 times above the upper limits of the institutional norm
- Patients must be able to provide written informed consent
- Women of childbearing potential must have a negative serum pregnancy test; the effects of AT-101 on the developing human fetus at the recommended therapeutic dose are unknown; for this reason and because Bcl-2 inhibitors have the potential to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation, and for at least one month following the last dose of AT-101; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
- Patients must have a Mini Mental State Exam score >= 15
Who cannot join
- Patients with serious concurrent infection or medical illness which would jeopardize the ability of the patient to receive the treatment outlined in this protocol with reasonable safety; (Examples of medical illnesses are [but not limited to] the following: uncontrolled hypertension, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situation that would limit compliance with study requirements)
- Patients who are pregnant or breast-feeding
- Patients who have received more than two prior treatments
- Patients who have been previously treated with gossypol, or have allergies to gossypol
- Patients receiving concurrent therapy for their tumor (i.e. chemotherapeutics or investigational agents); concurrent steroid use is allowed
- Patients with a concurrent malignancy are ineligible unless they are patients with curatively treated carcinoma-in-situ or basal cell carcinoma of the skin; patients with a prior malignancy are ineligible unless they have been free of disease for >= five years
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- Patients with ≥ Grade 2 sensory neuropathy based on the NCI CTCAE
- Patients who are taking iron supplements
- Patients with any condition (e.g., gastrointestinal tract disease resulting in an inability to take oral medication or a requirement for IV alimentation, prior surgical procedures affecting absorption, or active peptic ulcer disease) that impairs their ability to swallow pills are excluded
- Patients cannot be receiving cytochrome P450-inducing anticonvulsants (EIAEDs; e.g., phenytoin, carbamazepine, phenobarbital, primidone, oxcarbazepine)
- Patients with malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel are excluded; subjects with ulcerative colitis, inflammatory bowel disease, or a partial or complete small bowel obstruction are also excluded
- Eligibility of patients receiving any other medications or substances known to affect or with the potential to affect the activity or pharmacokinetics of AT-101 will be determined following review of their case by the Principal Investigator
- Patients with symptomatic hypercalcemia that is > Grade 2 (according to CTCAE)
- Requirement for routine use of hematopoietic growth factors (including granulocyte colony stimulating factor, granulocyte macrophage colony stimulating factor, or interleukin-11) or platelet transfusions to maintain absolute neutrophil counts or platelets counts above the required thresholds for study entry
- HIV-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with AT-101; in addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy; appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated
Trial locations and contacts
8 sites in 1 country.
8 sites in 1 country
United States8 sites
Johns Hopkins University
Baltimore, Maryland, 21287
University of Alabama at Birmingham
Birmingham, Alabama, 35294
Massachusetts General Hospital
Boston, Massachusetts, 02114
Cleveland Clinic Foundation
Cleveland, Ohio, 44195
Henry Ford Hospital
Detroit, Michigan, 48202
University of Pennsylvania
Philadelphia, Pennsylvania, 19104
Moffitt Cancer Center
Tampa, Florida, 33612
Wake Forest University Health Sciences
Winston-Salem, North Carolina, 27157
About this study
Official title: A Phase 2 Study of R-(-)-Gossypol (Ascenta's AT-101) in Recurrent Glioblastoma Multiforme
This phase II trial is studying how well gossypol works in treating patients with progressive or recurrent glioblastoma multiforme. Gossypol may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
Read the detailed description
PRIMARY OBJECTIVES:
- To estimate the overall survival rate associated with AT-101 in treating adult patients with recurrent glioblastoma multiforme.
SECONDARY OBJECTIVES:
- To assess and estimate the acute and late toxicities. II. Tumor response rate. III. To estimate 6-month progression free survival. IV. To explore associations of the clinical outcome (overall survival) among the changes of potential serum biomarkers, baseline tumor protein expression and gene methylation status.
OUTLINE: This is a multicenter study.
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.
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 06-methylguanine-DNA-methyltransferase (MGMT) gene methylation status. Blood samples are analyzed for apoptotic protein levels (Bcl-2) by enzyme-linked immunosorbent assay.
After completion of study therapy, patients are followed every 2 months.
- Conditions
- Adult Giant Cell Glioblastoma, Adult Glioblastoma, Adult Gliosarcoma, Recurrent Adult Brain Tumor
- Being tested
- R-(-)-gossypol acetic acid, laboratory biomarker analysis
- Medical subject headings
- Glioblastoma, Gliosarcoma, Brain Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
R-(-)-gossypol acetic acidDrug
Also called AT-101
Given PO
laboratory biomarker analysisOther
Correlative studies
| Study group | Role | What they receive |
|---|---|---|
| Treatment (R-(-)-gossypol acetic acid) | Experimental | 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. Receives: Drug: R-(-)-gossypol acetic acid; Other: laboratory biomarker analysis |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall Survival
The overall failure rate will be estimated along with 95% confidence intervals. A median time of survival will be estimated using standard methods.
Measured: 4.5 years
Secondary outcomes (3)
Percent of Patients With Grade 3 and 4 Adverse Events Related to Treatment
The proportion of patients with serious or life threatening (grade 3 and 4) toxicities will be estimated using NCI CTCAE
Measured: 3 years
Tumor Response Rate
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
Measured: 3 years
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
The probability of 6-month progression-free survival will be estimated using binomial distribution.
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Oct 2007 (estimated)
- Study startJan 2008
- Primary completionJun 2012
- Study completionJun 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Adult Giant Cell GlioblastomaStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 56 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- John Fiveash, MD, Principal investigator, National Cancer Institute (NCI)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00540722
- Sponsor's protocol ID
- NCI-2013-00018
- Other IDs
- 0702, CDR0000569405, ABTC-0702, NABTT 0702, U01CA062475
- Status last verified
- Jul 2017
- First submitted
- 5 Oct 2007
- Last updated
- 11 Aug 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 11 Aug 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2 Study of R-(-)-Gossypol (Ascenta's AT-101) in Recurrent Glioblastoma Multiforme
- ClinicalTrials.gov ID
- NCT00540722
- Acronym / sponsor ID
- NCI-2013-00018
- Conditions
- Adult Giant Cell Glioblastoma, Adult Glioblastoma, Adult Gliosarcoma, Recurrent Adult Brain Tumor
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 56 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- Jan 2008
- Primary completion
- Jun 2012 (actual)
- Study completion
- Jun 2012 (actual)
- First posted
- 8 Oct 2007 (estimated)
- Results
- Posted 12 Jul 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This phase II trial is studying how well gossypol works in treating patients with progressive or recurrent glioblastoma multiforme. Gossypol may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
Detailed description
PRIMARY OBJECTIVES:
- To estimate the overall survival rate associated with AT-101 in treating adult patients with recurrent glioblastoma multiforme.
SECONDARY OBJECTIVES:
- To assess and estimate the acute and late toxicities. II. Tumor response rate. III. To estimate 6-month progression free survival. IV. To explore associations of the clinical outcome (overall survival) among the changes of potential serum biomarkers, baseline tumor protein expression and gene methylation status.
OUTLINE: This is a multicenter study.
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.
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 06-methylguanine-DNA-methyltransferase (MGMT) gene methylation status. Blood samples are analyzed for apoptotic protein levels (Bcl-2) by enzyme-linked immunosorbent assay.
After completion of study therapy, patients are followed every 2 months.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (R-(-)-gossypol acetic acid) | Experimental | Drug: R-(-)-gossypol acetic acid, Other: laboratory biomarker analysisPatients 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Patients must have histologically confirmed supratentorial glioblastoma multiforme which is progressive or recurrent after radiation therapy ± chemotherapy; patients with previously low grade glioma who progressed after radiotherapy ± chemotherapy and are biopsied and found to have glioblastoma multiforme are eligible
- Patients must have tumor tissue form completed and signed by a pathologist
- Patients must have measurable contrast enhancing progressive or recurrent glioblastoma multiforme by MRI or CT imaging (Within 14 days before starting treatment)
- Patients must have recovered from toxicity of prior therapy; an interval of at least 3 months must have elapsed since the completion of the most recent course of radiation therapy, while at least 3 weeks must have elapsed since the completion of a non-nitrosourea containing chemotherapy regimen, and at least 6 weeks since the completion of a nitrosourea containing chemotherapy regimen; NOTE: For non-cytotoxic, FDA approved agents (i.e. celebrex, thalidomide, etc.) therapy could be started 2 weeks after discontinuing this agent provided the patient has fully recovered from all toxicity associated with the agent; for investigational, non-cytotoxic agents a minimum of 3 weeks must have elapsed before the patient will be eligible for this study
- Patients must have a Karnofsky performance status >= 60% (i.e. the patient must be able to care for himself/herself with occasional help from others)
Key exclusion criteria (15 listed)
- Patients with serious concurrent infection or medical illness which would jeopardize the ability of the patient to receive the treatment outlined in this protocol with reasonable safety; (Examples of medical illnesses are [but not limited to] the following: uncontrolled hypertension, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situation that would limit compliance with study requirements)
- Patients who are pregnant or breast-feeding
- Patients who have received more than two prior treatments
- Patients who have been previously treated with gossypol, or have allergies to gossypol
- Patients receiving concurrent therapy for their tumor (i.e. chemotherapeutics or investigational agents); concurrent steroid use is allowed
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 |
|---|---|---|
| R-(-)-gossypol acetic acidAlso: AT-101Given PO | Drug | Treatment (R-(-)-gossypol acetic acid) |
| laboratory biomarker analysisCorrelative studies | Other | Treatment (R-(-)-gossypol acetic acid) |
Primary outcome
Overall Survival
Time frame: 4.5 years
The overall failure rate will be estimated along with 95% confidence intervals. A median time of survival will be estimated using standard methods.
3 secondary outcomes
Percent of Patients With Grade 3 and 4 Adverse Events Related to Treatment
Time frame: 3 years
Tumor Response Rate
Time frame: 3 years
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
Time frame: 6 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Aug 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
Related trials for Adult Giant Cell Glioblastoma
Active, not recruitingPhase 1
Vorinostat and Temozolomide in Treating Patients With Malignant Gliomas
Adult Anaplastic Astrocytoma, Adult Anaplastic Oligodendroglioma
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.
John Fiveash, MD principal investigator
National Cancer Institute (NCI)
8 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing R-(-)-gossypol acetic acid and laboratory biomarker analysis in people with Adult Giant Cell Glioblastoma and Adult Glioblastoma, run by National Cancer Institute (NCI) at 8 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?
The sponsor lists 13 inclusion and 15 exclusion criteria. 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: finished, as of the sponsor's last update on 11 Aug 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 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 phase mean?
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?
Yes. Results are posted in the registry (first posted 12 Jul 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Overall Survival (time frame: 4.5 years). 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 11 Aug 2017.