Glioblastoma MultiformePhase 2NCT01402063
PPX and Concurrent Radiation for Newly Diagnosed Glioblastoma Without MGMT Methylation
A Phase 2 study testing PPX (CT2103) and Temozolomide in people with Glioblastoma Multiforme, run by Brown University at 9 sites in United States.
Trial summary
To obtain preliminary data in a randomized phase II study whether PPX/RT improves progression-free survival as compared to temozolomide/RT for patients with GBM without MGMT methylation. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Glioblastoma Multiforme
- What is being tested?
- PPX (CT2103) and Temozolomide
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 63 participants
- Where
- 9 sitesUnited States
- Study dates
- Sep 2011to Jun 2015
- 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
- Histologically proven diagnosis of glioblastoma or gliosarcoma (WHO grade IV)
- GBM must have unmethylated MGMT as determined by central laboratory
- Diagnosis of GBM must be made by biopsy or surgical excision, either partial or complete; as long as there is sufficient tissue to determine MGMT status
- No prior chemotherapy or radiation for brain tumor
- Must be able to tolerate brain MRIs.
- A diagnostic contrast-enhanced MRI must be performed postoperatively within 42 days prior to study registration.
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- KPS >60.
- Age > 18
- Life expectancy of at least 3 months.
- Absolute neutrophil count > 1500/mm3, Platelets > 100,000/mm,
- Creatinine < 2 x ULN
- ALT or AST < 3 x upper limit of normal (ULN) and total bilirubin < 1.5x ULN.
- Patients with a prior history of low grade glioma who did not receive prior radiation or chemotherapy with transformation to grade IV brain tumor are eligible.
- Women must be non-lactating, and surgically sterile, post-menopausal or have a negative serum pregnancy test and agree to use adequate birth control. Males must agree to use adequate birth control.
- Voluntary, signed informed consent.
Who cannot join
- Acute infection or other medical condition that would impair study treatment
- No other active invasive malignancy unless disease free for at least 3 years.
- Prior temozolomide or PPX.
- Prior use of Gliadel wafers or any other intratumoral or intracavitary treatment are not permitted.
- Prior radiotherapy to the head or neck (except for T1 glottic cancer), resulting in overlap of radiation fields.
- No diffuse leptomeningeal disease, or gliomatosis cerebri.
- Use of any other experimental chemotherapy drug within the 60 days prior to randomization and during the trial. (Use of a non-chemotherapy investigational agent must be approved by the Brown University Oncology Group)
Trial locations and contacts
9 sites in 1 country.
9 sites in 1 country
United States9 sites
UT Southwestern Cancer Center
Dallas, Texas, 75235
PSU
Hershey, Pennsylvania, 17033
UCSD Cancer Center
La Jolla, California, 92093
Thomas Jefferson University Cancer Center
Philadelphia, Pennsylvania, 19107
Rhode Island Hospital
Providence, Rhode Island, 02906
Maine Medical Center
Scarborough, Maine, 04074
University of Washington
Seattle, Washington, 98109
SUNY Medical Center
Syracuse, New York, 13210
UMASS Medical Center Cancer Center
Worcester, Massachusetts, 01605
About this study
Official title: PPX and Concurrent Radiation for Newly Diagnosed Glioblastoma Without MGMT Methylation: A Randomized Phase II Study
To obtain preliminary data in a randomized phase II study whether PPX/RT improves progression-free survival as compared to temozolomide/RT for patients with GBM without MGMT methylation.
Read the detailed description
To evaluate the toxicities of PPX/RT To evaluate neuro-cognitive functional assessments of patients with GBM receiving PPX/RT To obtain preliminary data in a randomized phase II study whether PPX/RT improves overall survival as compared to temozolomide /RT for patients with GBM without MGMT methylation to facilitate planning a phase III study.
- Conditions
- Glioblastoma Multiforme
- Being tested
- PPX (CT2103), Temozolomide
- Keywords
- Brain Tumors, Glioblastoma Multiforme, GBM
- Medical subject headings
- Glioblastoma, Brain Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PPX (CT2103)Drug
XRT: 60 Gy at 2 Gy/fraction x 30 fractions PPX: 50 mg/m2/week x 6 weeks during radiation Temozolomide maintenance: Beginning 4 weeks after completion of chemoradiation, temozolomide d1-5 of 28 day cycle for 12 cycle maximum.
TemozolomideDrug
XRT: 60 Gy at 2 Gy/fraction x 30 fractions Temozolomide, 75 mg/m2/day, 7 days per week, from the first to the last day of radiotherapy Temozolomide maintenance: Beginning 4 weeks after completion of chemoradiation, temozolomide d1-5 of 28 day cycle for 12 cycle maximum
| Study group | Role | What they receive |
|---|---|---|
| radiation plus PPX(CT2103 | Experimental | Radiation therapy, Monday through Friday, for 6 weeks for a total of 30 treatments
+ intravenous PPX every week x 6 weeks for a total of 6 treatments Receives: Drug: PPX (CT2103) |
| radiation + Temozolomide | Active comparator | Radiation therapy, Monday through Friday, for 6 weeks for a total of 30 treatments
+ Daily oral temozolomide(TMZ) (7 days) x 6 wks for a total of 42 days Receives: Drug: Temozolomide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression Free Survival PPX/RT Versus TMZ/RT for Patients With GBM Without Methylation
MRI response evaluated by RANO criteria
- Complete Response (CR): Circumstance when the enhancing tumor is no longer seen by neuroimaging, with the patient off all steroids or on adrenal maintenance only; CR will be coded only if confirmed by a second CT/MR scan performed a minimum of 4 weeks after the initial scan coding a response.
- Partial Response (PR): Decrease of > 50% in the product of two diameters. Patients should be receiving stable or decreasing doses of steroids. PR will be coded only if confirmed by a second CT/MR scan performed a minimum of 4 weeks after the initial scan.
- Progression (P): A > 25% increase in tumor area (two diameters) provided that the patient has not had his/her dose of steroids decreased since the last evaluation period. This will not need a confirmatory scan. A concomitant decrease in steroid dose will rule out a progression designation during the first 2 months after completion of XRT.
Measured: Q 3 months on study then Q3 months in f/u for yr 1, q 4 months yr 2, q 6 months for approximately 4 ys.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Jul 2011 (estimated)
- Study startSep 2011
- Primary completionApr 2014
- Study completionJun 2015
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.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Glioblastoma MultiformeStudies of the same condition, open and under way.
- More trials run by Brown UniversityThe 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
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 63 participants (actual)
Sponsor and investigators
- Lead sponsor
- Brown University
- Sponsor type
- University, hospital or other
- Collaborators
- Rhode Island Hospital, Milton S. Hershey Medical Center, University of Washington, University of Massachusetts, Worcester, MaineHealth, University of California, San Diego, Thomas Jefferson University
- Responsible party
- Principal investigator, howard safran, Brown University
- Investigators
- Howard Safran, MD, Principal investigator, BrUOG
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01402063
- Sponsor's protocol ID
- BrUOG 244
- Status last verified
- Feb 2020
- First submitted
- 8 Jul 2011
- Last updated
- 17 Feb 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Jeyapalan S, Boxerman J, Donahue J, Goldman M, Kinsella T, Dipetrillo T, Evans D, Elinzano H, Constantinou M, Stopa E, Puthawala Y, Cielo D, Santaniello A, Oyelese A, Mantripragada K, Rosati K, Isdale D, Safran H; Brown University Oncology Group Study. Paclitaxel poliglumex, temozolomide, and radiation for newly diagnosed high-grade glioma: a Brown University Oncology Group Study. Am J Clin Oncol. 2014 Oct;37(5):444-9. doi: 10.1097/COC.0b013e31827de92b.
PubMed 23388562
Study at a glance
From the registry record, last updated by the sponsor on 17 Feb 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- PPX and Concurrent Radiation for Newly Diagnosed Glioblastoma Without MGMT Methylation: A Randomized Phase II Study
- ClinicalTrials.gov ID
- NCT01402063
- Acronym / sponsor ID
- BrUOG 244
- Conditions
- Glioblastoma Multiforme
- Keywords
- Brain Tumors, Glioblastoma Multiforme, GBM
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 63 participants (actual)
- Lead sponsor
- Brown UniversityUniversity, hospital or other
- Collaborators
- Rhode Island Hospital, Milton S. Hershey Medical Center, University of Washington, University of Massachusetts, Worcester, MaineHealth, University of California, San Diego, Thomas Jefferson University
- Study start
- Sep 2011
- Primary completion
- Apr 2014 (actual)
- Study completion
- Jun 2015 (actual)
- First posted
- 26 Jul 2011 (estimated)
- Results
- Posted 11 Jun 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
To obtain preliminary data in a randomized phase II study whether PPX/RT improves progression-free survival as compared to temozolomide/RT for patients with GBM without MGMT methylation.
Detailed description
To evaluate the toxicities of PPX/RT To evaluate neuro-cognitive functional assessments of patients with GBM receiving PPX/RT To obtain preliminary data in a randomized phase II study whether PPX/RT improves overall survival as compared to temozolomide /RT for patients with GBM without MGMT methylation to facilitate planning a phase III study.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| radiation plus PPX(CT2103 | Experimental | Drug: PPX (CT2103)Radiation therapy, Monday through Friday, for 6 weeks for a total of 30 treatments + intravenous PPX every week x 6 weeks for a total of 6 treatments |
| radiation + Temozolomide | Active comparator | Drug: TemozolomideRadiation therapy, Monday through Friday, for 6 weeks for a total of 30 treatments + Daily oral temozolomide(TMZ) (7 days) x 6 wks for a total of 42 days |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- Histologically proven diagnosis of glioblastoma or gliosarcoma (WHO grade IV)
- GBM must have unmethylated MGMT as determined by central laboratory
- Diagnosis of GBM must be made by biopsy or surgical excision, either partial or complete; as long as there is sufficient tissue to determine MGMT status
- No prior chemotherapy or radiation for brain tumor
- Must be able to tolerate brain MRIs.
Key exclusion criteria (7 listed)
- Acute infection or other medical condition that would impair study treatment
- No other active invasive malignancy unless disease free for at least 3 years.
- Prior temozolomide or PPX.
- Prior use of Gliadel wafers or any other intratumoral or intracavitary treatment are not permitted.
- Prior radiotherapy to the head or neck (except for T1 glottic cancer), resulting in overlap of radiation fields.
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 |
|---|---|---|
| PPX (CT2103)XRT: 60 Gy at 2 Gy/fraction x 30 fractions PPX: 50 mg/m2/week x 6 weeks during radiation Temozolomide maintenance: Beginning 4 weeks after completion of chemoradiation, temozolomide d1-5 of 28 day cycle for 12 cycle maximum. | Drug | radiation plus PPX(CT2103 |
| TemozolomideXRT: 60 Gy at 2 Gy/fraction x 30 fractions Temozolomide, 75 mg/m2/day, 7 days per week, from the first to the last day of radiotherapy Temozolomide maintenance: Beginning 4 weeks after completion of chemoradiation, temozolomide d1-5 of 28 day cycle for 12 cycle maximum | Drug | radiation + Temozolomide |
Primary outcome
Progression Free Survival PPX/RT Versus TMZ/RT for Patients With GBM Without Methylation
Time frame: Q 3 months on study then Q3 months in f/u for yr 1, q 4 months yr 2, q 6 months for approximately 4 ys.
MRI response evaluated by RANO criteria * Complete Response (CR): Circumstance when the enhancing tumor is no longer seen by neuroimaging, with the patient off all steroids or on adrenal maintenance only; CR will be coded only if confirmed by a second CT/MR scan performed a minimum of 4 weeks after the initial scan coding a response. * Partial Response (PR): Decrease of > 50% in the product of two diameters. Patients should be receiving stable or decreasing doses of steroids. PR will be coded only if confirmed by a second CT/MR scan performed a minimum of 4 weeks after the initial scan. * Progression (P): A > 25% increase in tumor area (two diameters) provided that the patient has not had his/her dose of steroids decreased since the last evaluation period. This will not need a confirmatory scan. A concomitant decrease in steroid dose will rule out a progression designation during the first 2 months after completion of XRT.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Feb 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 23388562Jeyapalan S, Boxerman J, Donahue J, Goldman M, Kinsella T, Dipetrillo T, Evans D, Elinzano H, Constantinou M, Stopa E, Puthawala Y, Cielo D, Santaniello A, Oyelese A, Mantripragada K, Rosati K, Isdale D, Safran H; Brown University Oncology Group Study. Paclitaxel poliglumex, temozolomide, and radiation for newly diagnosed high-grade glioma: a Brown University Oncology Group Study. Am J Clin Oncol. 2014 Oct;37(5):444-9. doi: 10.1097/COC.0b013e31827de92b.
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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.
Howard Safran, MD principal investigator
BrUOG
9 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 PPX (CT2103) and Temozolomide in people with Glioblastoma Multiforme, run by Brown University at 9 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 15 inclusion and 7 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 17 Feb 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 9 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 11 Jun 2015). 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?
Progression Free Survival PPX/RT Versus TMZ/RT for Patients With GBM Without Methylation (time frame: Q 3 months on study then Q3 months in f/u for yr 1, q 4 months yr 2, q 6 months for approximately 4 ys.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01402063, which also lists 1 linked publication.
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 17 Feb 2020.