PPX and Concurrent Radiation for Newly Diagnosed Glioblastoma Without MGMT Methylation

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.

Study Overview

• Status: Completed
• Conditions: Glioblastoma Multiforme
• Intervention / Treatment: Drug: PPX (CT2103); Drug: Temozolomide

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 Type: Interventional
• Enrollment (Actual): 63
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • La Jolla, California, United States, 92093
      • UCSD Cancer Center
  • Maine
    • Scarborough, Maine, United States, 04074
      • Maine Medical Center
  • Massachusetts
    • Worcester, Massachusetts, United States, 01605
      • UMASS Medical Center Cancer Center
  • New York
    • Syracuse, New York, United States, 13210
      • SUNY Medical Center
  • Pennsylvania
    • Hershey, Pennsylvania, United States, 17033
      • PSU
    • Philadelphia, Pennsylvania, United States, 19107
      • Thomas Jefferson University Cancer Center
  • Rhode Island
    • Providence, Rhode Island, United States, 02906
      • Rhode Island Hospital
  • Texas
    • Dallas, Texas, United States, 75235
      • UT Southwestern Cancer Center
  • Washington
    • Seattle, Washington, United States, 98109
      • University of Washington

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.

Collaborators and Investigators

• Sponsor: Brown University
• Collaborators: University of California, San Diego; Milton S. Hershey Medical Center; University of Washington; Rhode Island Hospital; Thomas Jefferson University; University of Massachusetts, Worcester; MaineHealth
• Investigators: Principal Investigator: Howard Safran, MD, BrUOG

Publications and helpful links

General 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.

Study record dates

Study Major Dates

• Study Start: September 1, 2011
• Primary Completion (Actual): April 1, 2014
• Study Completion (Actual): June 1, 2015

Study Registration Dates

• First Submitted: July 8, 2011
• First Submitted That Met QC Criteria: July 25, 2011
• First Posted (Estimate): July 26, 2011

Study Record Updates

• Last Update Posted (Actual): February 17, 2020
• Last Update Submitted That Met QC Criteria: February 13, 2020
• Last Verified: February 1, 2020

More Information

Terms related to this study

• Keywords: Glioblastoma Multiforme; GBM; Brain Tumors
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Glioblastoma; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Alkylating; Alkylating Agents; Temozolomide; Paclitaxel poliglumex
• Other Study ID Numbers: BrUOG 244