PPX and Concurrent Radiation for Newly Diagnosed Glioblastoma Without MGMT Methylation

Phase 2

Completed

• Conditions: Glioblastoma Multiforme
• Interventions: Drug: PPX (CT2103); Drug: Temozolomide

• Registration Number: NCT01402063
• Lead Sponsor: Brown University

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.

Study Timeline

• Study First Submitted: 2011-07-08
• Study First Submitted QC: 2011-07-25
• Study First Posted: 2011-07-26
• Study Start: 2011-09
• Primary Completion: 2014-04
• Results First Submitted: 2015-04-30
• Study Completion: 2015-06
• Results First Submitted QC: 2015-06-09
• Results First Posted: 2015-06-11
• Status Verified: 2020-02
• Last Update Submitted: 2020-02-13
• Last Update Posted: 2020-02-17

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 63

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
radiation plus PPX(CT2103	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	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

Primary Outcome Measures

Name	Time	Method
Progression Free Survival PPX/RT Versus TMZ/RT for Patients With GBM Without Methylation	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.

Trial Locations

Locations (9)

Thomas Jefferson University Cancer Center; 🇺🇸 Philadelphia, Pennsylvania, United States

UT Southwestern Cancer Center; 🇺🇸 Dallas, Texas, United States

University of Washington; 🇺🇸 Seattle, Washington, United States

UCSD Cancer Center; 🇺🇸 La Jolla, California, United States

Maine Medical Center; 🇺🇸 Scarborough, Maine, United States

UMASS Medical Center Cancer Center; 🇺🇸 Worcester, Massachusetts, United States

SUNY Medical Center; 🇺🇸 Syracuse, New York, United States

PSU; 🇺🇸 Hershey, Pennsylvania, United States

Rhode Island Hospital; 🇺🇸 Providence, Rhode Island, United States