PPX and Concurrent Radiation for Newly Diagnosed Glioblastoma Without MGMT Methylation

Glioblastoma Multiforme Clinical Trial

Official title:

PPX and Concurrent Radiation for Newly Diagnosed Glioblastoma Without MGMT Methylation: A Randomized Phase II Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01402063
• Other study ID #: BrUOG 244
• Status: Completed
• Phase: Phase 2
• Start date: September 2011
• Est. completion date: June 2015

Study information

• Verified date: February 2020
• Source: Brown University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 63
• Est. completion date: June 2015
• Est. primary completion date: April 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• Glioblastoma
• Glioblastoma Multiforme

Intervention

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.
• 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

Locations

Country	Name	City	State
United States	UT Southwestern Cancer Center	Dallas	Texas
United States	PSU	Hershey	Pennsylvania
United States	UCSD Cancer Center	La Jolla	California
United States	Thomas Jefferson University Cancer Center	Philadelphia	Pennsylvania
United States	Rhode Island Hospital	Providence	Rhode Island
United States	Maine Medical Center	Scarborough	Maine
United States	University of Washington	Seattle	Washington
United States	SUNY Medical Center	Syracuse	New York
United States	UMASS Medical Center Cancer Center	Worcester	Massachusetts

Sponsors (8)

Lead Sponsor	Collaborator
Brown University	Maine Medical Center, Milton S. Hershey Medical Center, Rhode Island Hospital, Thomas Jefferson University, University of California, San Diego, University of Massachusetts, Worcester, University of Washington

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.