PPX and Concurrent Radiation for Newly Diagnosed Glioblastoma Without MGMT Methylation

NCT01402063 | Completed Phase 2 Results DMC

• 1 other identifier: BrUOG 244
• Study Type: interventional
• Target: 63
• Locations: 1 country
• Sites: 9

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.

Conditions

Glioblastoma Multiforme

Keywords

Brain Tumors; Glioblastoma Multiforme; GBM

Outcome Measures

Primary Outcomes (1)

• 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.

Study Arms (2)

radiation plus PPX(CT2103

EXPERIMENTAL

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)

radiation + Temozolomide

ACTIVE COMPARATOR

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

Interventions

PPX (CT2103) DRUG

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.

radiation plus PPX(CT2103

Temozolomide DRUG

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

radiation + Temozolomide

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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)

Sponsors & Collaborators

• Brown University: lead
• Rhode Island Hospital: collaborator
• Milton S. Hershey Medical Center: collaborator
• University of Washington: collaborator
• University of Massachusetts, Worcester: collaborator
• MaineHealth: collaborator
• University of California, San Diego: collaborator
• Thomas Jefferson University: collaborator

Study Sites (9)

UCSD Cancer Center

La Jolla, California, 92093, United States

Location

Maine Medical Center

Scarborough, Maine, 04074, United States

Location

UMASS Medical Center Cancer Center

Worcester, Massachusetts, 01605, United States

Location

SUNY Medical Center

Syracuse, New York, 13210, United States

Location

PSU

Hershey, Pennsylvania, 17033, United States

Location

Thomas Jefferson University Cancer Center

Philadelphia, Pennsylvania, 19107, United States

Location

Rhode Island Hospital

Providence, Rhode Island, 02906, United States

Location

UT Southwestern Cancer Center

Dallas, Texas, 75235, United States

Location

University of Washington

Seattle, Washington, 98109, United States

Location

Related Publications (1)

• 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.

  PMID: 23388562 DERIVED

MeSH Terms

Conditions

Glioblastoma; Brain Neoplasms

Interventions

protein phosphatase 4; paclitaxel poliglumex; Temozolomide

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Howard Safran, MD
• Organization: Brown University Oncology Research Group (BrUOG)

kayla_rosati@brown.edu

4018633000

Study Officials

• Howard Safran, MD

  BrUOG

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: July 8, 2011
• First Posted: July 26, 2011
• Study Start: September 1, 2011
• Primary Completion: April 1, 2014
• Study Completion: June 1, 2015
• Last Updated: February 17, 2020
• Results First Posted: June 11, 2015

Record last verified: 2020-02

Locations

US (9)