PPX and Concurrent Radiation for Newly Diagnosed Glioblastoma Without MGMT Methylation

This study has been completed.
Sponsor:
Collaborators:
Rhode Island Hospital
Milton S. Hershey Medical Center
University of Washington
University of Massachusetts, Worcester
Maine Medical Center
University of California, San Diego
Thomas Jefferson University
Information provided by (Responsible Party):
howard safran, Brown University
ClinicalTrials.gov Identifier:
NCT01402063
First received: July 8, 2011
Last updated: June 9, 2015
Last verified: June 2015
  Purpose

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.


Condition Intervention Phase
Glioblastoma Multiforme
Drug: PPX (CT2103)
Drug: Temozolomide
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: PPX and Concurrent Radiation for Newly Diagnosed Glioblastoma Without MGMT Methylation: A Randomized Phase II Study

Resource links provided by NLM:


Further study details as provided by Brown University:

Primary Outcome Measures:
  • 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 5 ys. The cut-off represents approx. 4 yrs to align with the recently written manuscript and as study is now terminated. ] [ Designated as safety issue: No ]

    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.


Enrollment: 63
Study Start Date: September 2011
Study Completion Date: June 2015
Primary Completion Date: April 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: radiation plus 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

Drug: 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.
Active Comparator: radiation + Temozolomide

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

Drug: Temozolomide
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

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01402063

Locations
United States, California
UCSD Cancer Center
La Jolla, California, United States, 92093
United States, Maine
Maine Medical Center
Scarborough, Maine, United States, 04074
United States, Massachusetts
UMASS Medical Center Cancer Center
Worcester, Massachusetts, United States, 01605
United States, New York
SUNY Medical Center
Syracuse, New York, United States, 13210
United States, Pennsylvania
PSU
Hershey, Pennsylvania, United States, 17033
Thomas Jefferson University Cancer Center
Philadelphia, Pennsylvania, United States, 19107
United States, Rhode Island
Rhode Island Hospital
Providence, Rhode Island, United States, 02906
United States, Texas
UT Southwestern Cancer Center
Dallas, Texas, United States, 75235
United States, Washington
University of Washington
Seattle, Washington, United States, 98109
Sponsors and Collaborators
Brown University
Rhode Island Hospital
Milton S. Hershey Medical Center
University of Washington
University of Massachusetts, Worcester
Maine Medical Center
University of California, San Diego
Thomas Jefferson University
Investigators
Principal Investigator: Howard Safran, MD BrUOG
  More Information

No publications provided by Brown University

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: howard safran, Principal Investigator, Brown University
ClinicalTrials.gov Identifier: NCT01402063     History of Changes
Other Study ID Numbers: BrUOG 244
Study First Received: July 8, 2011
Results First Received: April 30, 2015
Last Updated: June 9, 2015
Health Authority: United States: Food and Drug Administration

Keywords provided by Brown University:
Brain Tumors
Glioblastoma Multiforme
GBM

Additional relevant MeSH terms:
Glioblastoma
Astrocytoma
Glioma
Neoplasms
Neoplasms by Histologic Type
Neoplasms, Germ Cell and Embryonal
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Temozolomide
Alkylating Agents
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on June 30, 2015