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PPX and Concurrent Radiation for Newly Diagnosed Glioblastoma Without MGMT Methylation

Primary Purpose

Glioblastoma Multiforme

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
PPX (CT2103)
Temozolomide
Sponsored by
Brown University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Glioblastoma Multiforme focused on measuring Brain Tumors, Glioblastoma Multiforme, GBM

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • 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.

  • 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.

Exclusion Criteria:

  • 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)

Sites / Locations

  • UCSD Cancer Center
  • Maine Medical Center
  • UMASS Medical Center Cancer Center
  • SUNY Medical Center
  • PSU
  • Thomas Jefferson University Cancer Center
  • Rhode Island Hospital
  • UT Southwestern Cancer Center
  • University of Washington

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

radiation plus PPX(CT2103

radiation + Temozolomide

Arm Description

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 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

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Full Information

First Posted
July 8, 2011
Last Updated
February 13, 2020
Sponsor
Brown University
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
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1. Study Identification

Unique Protocol Identification Number
NCT01402063
Brief Title
PPX and Concurrent Radiation for Newly Diagnosed Glioblastoma Without MGMT Methylation
Official Title
PPX and Concurrent Radiation for Newly Diagnosed Glioblastoma Without MGMT Methylation: A Randomized Phase II Study
Study Type
Interventional

2. Study Status

Record Verification Date
February 2020
Overall Recruitment Status
Completed
Study Start Date
September 2011 (undefined)
Primary Completion Date
April 2014 (Actual)
Study Completion Date
June 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Brown University
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

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Glioblastoma Multiforme
Keywords
Brain Tumors, Glioblastoma Multiforme, GBM

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
63 (Actual)

8. Arms, Groups, and Interventions

Arm Title
radiation plus PPX(CT2103
Arm Type
Experimental
Arm Description
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
Arm Title
radiation + Temozolomide
Arm Type
Active Comparator
Arm Description
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
Intervention Type
Drug
Intervention Name(s)
PPX (CT2103)
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Temozolomide
Intervention Description
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
Primary Outcome Measure Information:
Title
Progression Free Survival PPX/RT Versus TMZ/RT for Patients With GBM Without Methylation
Description
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.
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.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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. 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. Exclusion Criteria: 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)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Howard Safran, MD
Organizational Affiliation
BrUOG
Official's Role
Principal Investigator
Facility Information:
Facility Name
UCSD Cancer Center
City
La Jolla
State/Province
California
ZIP/Postal Code
92093
Country
United States
Facility Name
Maine Medical Center
City
Scarborough
State/Province
Maine
ZIP/Postal Code
04074
Country
United States
Facility Name
UMASS Medical Center Cancer Center
City
Worcester
State/Province
Massachusetts
ZIP/Postal Code
01605
Country
United States
Facility Name
SUNY Medical Center
City
Syracuse
State/Province
New York
ZIP/Postal Code
13210
Country
United States
Facility Name
PSU
City
Hershey
State/Province
Pennsylvania
ZIP/Postal Code
17033
Country
United States
Facility Name
Thomas Jefferson University Cancer Center
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19107
Country
United States
Facility Name
Rhode Island Hospital
City
Providence
State/Province
Rhode Island
ZIP/Postal Code
02906
Country
United States
Facility Name
UT Southwestern Cancer Center
City
Dallas
State/Province
Texas
ZIP/Postal Code
75235
Country
United States
Facility Name
University of Washington
City
Seattle
State/Province
Washington
ZIP/Postal Code
98109
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
23388562
Citation
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.
Results Reference
derived

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PPX and Concurrent Radiation for Newly Diagnosed Glioblastoma Without MGMT Methylation

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