Motexafin Gadolinium, Temozolomide, and Radiation Therapy in Treating Patients With Newly Diagnosed Glioblastoma Multiforme or Gliosarcoma

NCT ID: NCT00305864

Last Updated: 2018-03-05

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1/PHASE2

Total Enrollment

118 participants

Study Classification

INTERVENTIONAL

Study Start Date

2006-02-09

Study Completion Date

2011-03-15

Brief Summary

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This phase I/II trial is studying the side effects and best dose of motexafin gadolinium when given together with temozolomide and radiation therapy and to see how well they work in treating patients with newly diagnosed supratentorial glioblastoma multiforme or gliosarcoma. Drugs used in chemotherapy, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Motexafin gadolinium may help temozolomide work better by making tumor cells more sensitive to the drug. Radiation therapy uses high-energy x-rays to kill tumor cells. Motexafin gadolinium may also make tumor cells more sensitive to radiation therapy. Giving motexafin gadolinium together with temozolomide and radition therapy may kill more tumor cells.

Detailed Description

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PRIMARY OBJECTIVES:

I. Determine the maximum tolerated dose of motexafin gadolinium (MGd) when given concurrently with temozolomide and radiotherapy in patients with newly diagnosed supratentorial glioblastoma multiforme (GBM) or gliosarcoma.

II. Estimate the overall survival of patients treated with concurrent radiotherapy, temozolomide, and MGd followed by post-radiation temozolomide.

III. Determine the short- and long-term adverse effects in patients treated with this treatment.

IV. Estimate the progression-free survival of patients with newly diagnosed supratentorial GBM or gliosarcoma treated with this regimen.

OUTLINE: This is a multicenter, dose-escalation study of motexafin gadolinium (MGd).

PHASE I: Patients undergo radiotherapy once daily on days 1-5, 8-12, 15-19, 22-26, 29-33, and 36-40. Beginning the night before the first dose of radiotherapy and ending the night before the last dose of radiotherapy, patients receive concurrent oral temozolomide once daily on days 0-39. Patients also receive MGd IV over 30 minutes prior to radiotherapy once daily on days 1-5 and 8-12 and then on days 15, 17, 19, 22, 24, 26, 29, 31, 33, 36, 38, and 40. Beginning 28 days after the completion of radiotherapy, patients receive oral temozolomide once daily on days 1-5. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-7 patients receive escalating doses of MGd until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which no more than 6 eligible patients experience dose-limiting toxicity.

PHASE II: Patients undergo radiotherapy and receive temozolomide as in phase I. Patients also receive MGd as in phase I at the MTD determined in phase I.

After completion of study treatment, patients are followed every 2 months for 1 year, every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.

Conditions

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Adult Giant Cell Glioblastoma Adult Glioblastoma Adult Gliosarcoma

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Phase I: MGd 3 mg/kg

Patients undergo radiotherapy once daily on days 1-5, 8-12, 15-19, 22-26, 29-33, and 36-40. Beginning the night before the first dose of radiotherapy and ending the night before the last dose of radiotherapy, patients receive concurrent oral temozolomide once daily on days 0-39. Patients also receive MGd IV over 30 minutes prior to radiotherapy once daily on days 1-5 and 8-12 and then on days 15, 17, 19, 22, 24, 26, 29, 31, 33, 36, 38, and 40. Beginning 28 days after the completion of radiotherapy, patients receive oral temozolomide once daily on days 1-5. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.

Group Type EXPERIMENTAL

3-Dimensional Conformal Radiation Therapy

Intervention Type RADIATION

Undergo radiotherapy

Motexafin Gadolinium

Intervention Type DRUG

Given IV

Temozolomide

Intervention Type DRUG

Given orally

Phase I: MGd 4 mg/kg

Patients undergo radiotherapy once daily on days 1-5, 8-12, 15-19, 22-26, 29-33, and 36-40. Beginning the night before the first dose of radiotherapy and ending the night before the last dose of radiotherapy, patients receive concurrent oral temozolomide once daily on days 0-39. Patients also receive MGd IV over 30 minutes prior to radiotherapy once daily on days 1-5 and 8-12 and then on days 15, 17, 19, 22, 24, 26, 29, 31, 33, 36, 38, and 40.Beginning 28 days after the completion of radiotherapy, patients receive oral temozolomide once daily on days 1-5. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.

Group Type EXPERIMENTAL

3-Dimensional Conformal Radiation Therapy

Intervention Type RADIATION

Undergo radiotherapy

Motexafin Gadolinium

Intervention Type DRUG

Given IV

Temozolomide

Intervention Type DRUG

Given orally

Phase I: MGd 5 mg/kg

Patients undergo radiotherapy once daily on days 1-5, 8-12, 15-19, 22-26, 29-33, and 36-40. Beginning the night before the first dose of radiotherapy and ending the night before the last dose of radiotherapy, patients receive concurrent oral temozolomide once daily on days 0-39. Patients also receive MGd IV over 30 minutes prior to radiotherapy once daily on days 1-5 and 8-12 and then on days 15, 17, 19, 22, 24, 26, 29, 31, 33, 36, 38, and 40. Beginning 28 days after the completion of radiotherapy, patients receive oral temozolomide once daily on days 1-5.Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.

Group Type EXPERIMENTAL

3-Dimensional Conformal Radiation Therapy

Intervention Type RADIATION

Undergo radiotherapy

Motexafin Gadolinium

Intervention Type DRUG

Given IV

Temozolomide

Intervention Type DRUG

Given orally

Phase II: MGd 5 mg/kg

Patients undergo radiotherapy once daily on days 1-5, 8-12, 15-19, 22-26, 29-33, and 36-40. Beginning the night before the first dose of radiotherapy and ending the night before the last dose of radiotherapy, patients receive concurrent oral temozolomide once daily on days 0-39. Patients also receive MGd IV over 30 minutes prior to radiotherapy once daily on days 1-5 and 8-12 and then on days 15, 17, 19, 22, 24, 26, 29, 31, 33, 36, 38, and 40. Beginning 28 days after the completion of radiotherapy, patients receive oral temozolomide once daily on days 1-5. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.

Group Type ACTIVE_COMPARATOR

3-Dimensional Conformal Radiation Therapy

Intervention Type RADIATION

Undergo radiotherapy

Motexafin Gadolinium

Intervention Type DRUG

Given IV

Temozolomide

Intervention Type DRUG

Given orally

Interventions

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3-Dimensional Conformal Radiation Therapy

Undergo radiotherapy

Intervention Type RADIATION

Motexafin Gadolinium

Given IV

Intervention Type DRUG

Temozolomide

Given orally

Intervention Type DRUG

Other Intervention Names

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3-dimensional radiation therapy 3D CONFORMAL RADIATION THERAPY 3D CRT 3D-CRT Conformal Therapy Radiation Conformal Therapy API-GP3 gadolinium texaphyrin Gd (III) Texaphryin Gd-Tex PCI-0120 Xcytrin CCRG-81045 Imidazo[5,1-d]-1,2,3,5-tetrazine-8-carboxamide, 3, 4-dihydro-3-methyl-4-oxo- M & B 39831 M and B 39831 Methazolastone RP-46161 SCH 52365 Temcad Temodal Temodar Temomedac

Eligibility Criteria

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Inclusion Criteria

* Histologically confirmed glioblastoma multiforme (GBM) or gliosarcoma

* Newly diagnosed by surgical biopsy or excision within the past 5 weeks
* Supratentorial location, as determined by the following:

* Contrast-enhanced MRI performed preoperatively
* MRI performed postoperatively within 28 days prior to study entry (preferably within 72 hours of surgery)
* Postoperative scan not required if diagnosed by stereotactic biopsy and pre-operative MRI was performed
* No gliomas graded \< GBM
* No recurrent malignant gliomas
* No tumor foci detected below the tentorium or beyond the cranial vault
* No multifocal disease or leptomeningeal spread
* Zubrod performance status 0-1
* Neurologic function status 0-2
* Absolute neutrophil count ≥ 1,800 cells/mm\^3
* Platelet count ≥ 100,000 cells/mm\^3
* Hemoglobin ≥ 8 g/dL (transfusion allowed)
* BUN ≤ 25 mg/dL
* Creatinine ≤ 1.5 mg/dL
* Bilirubin ≤ 1.5 mg/dL
* ALT or AST ≤ 2 times upper limit of normal
* Fertile patients must use effective contraception during and for 2 months after completion of study treatment
* Negative pregnancy test
* Not pregnant or nursing
* No prior invasive malignancies, except for nonmelanomatous skin cancer and carcinoma in situ of the uterine cervix or bladder, unless disease-free for ? 3 years
* No severe, active comorbidity, defined as follows:

* Unstable angina and/or congestive heart failure requiring hospitalization within the past 6 months
* Transmural myocardial infarction within the past 6 months
* Acute bacterial or fungal infection requiring intravenous antibiotics at study entry
* Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy within 30 days prior to study entry
* Coagulation defects
* Known AIDS
* No prior allergic reaction to the study drugs
* No history of porphyria or G6PD deficiency
* No allergy to gadolinium or contraindications to MRI
* No other concurrent chemotherapy
* Recovered from effects of surgery or postoperative infection and other complications
* No prior systemic chemotherapy, including polifeprosan 20 with carmustine implant (Gliadel wafer), for the current GBM

* Prior chemotherapy for a different cancer allowed
* No prior radiotherapy to the head and neck (except for T1 glottic cancer) that would result in overlap of radiation therapy fields
* No prophylactic filgrastim (G-CSF) during the first course of study treatment
* No concurrent sargramostim (GM-CSF)
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Radiation Therapy Oncology Group

NETWORK

Sponsor Role collaborator

National Cancer Institute (NCI)

NIH

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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David Brachman

Role: PRINCIPAL_INVESTIGATOR

Radiation Therapy Oncology Group

Locations

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Mobile Infirmary Medical Center

Mobile, Alabama, United States

Site Status

Arizona Oncology Services Foundation

Scottsdale, Arizona, United States

Site Status

The University of Arizona Medical Center-University Campus

Tucson, Arizona, United States

Site Status

East Bay Radiation Oncology Center

Castro Valley, California, United States

Site Status

Eden Hospital Medical Center

Castro Valley, California, United States

Site Status

Valley Medical Oncology Consultants-Castro Valley

Castro Valley, California, United States

Site Status

Bay Area Breast Surgeons Inc

Emeryville, California, United States

Site Status

Valley Medical Oncology Consultants-Fremont

Fremont, California, United States

Site Status

Saint Rose Hospital

Hayward, California, United States

Site Status

Los Angeles County-USC Medical Center

Los Angeles, California, United States

Site Status

USC / Norris Comprehensive Cancer Center

Los Angeles, California, United States

Site Status

Contra Costa Regional Medical Center

Martinez, California, United States

Site Status

El Camino Hospital

Mountain View, California, United States

Site Status

Highland General Hospital

Oakland, California, United States

Site Status

Alta Bates Summit Medical Center - Summit Campus

Oakland, California, United States

Site Status

Bay Area Tumor Institute

Oakland, California, United States

Site Status

Hematology and Oncology Associates-Oakland

Oakland, California, United States

Site Status

Tom K Lee Inc

Oakland, California, United States

Site Status

Stanford Cancer Institute Palo Alto

Palo Alto, California, United States

Site Status

Valley Care Health System - Pleasanton

Pleasanton, California, United States

Site Status

Valley Medical Oncology Consultants

Pleasanton, California, United States

Site Status

Doctors Medical Center- JC Robinson Regional Cancer Center

San Pablo, California, United States

Site Status

Denver Veterans Administration Medical Center

Denver, Colorado, United States

Site Status

University of Florida Health Science Center - Gainesville

Gainesville, Florida, United States

Site Status

University of Florida Health Science Center - Jacksonville

Jacksonville, Florida, United States

Site Status

University of Miami Miller School of Medicine-Sylvester Cancer Center

Miami, Florida, United States

Site Status

Rush - Copley Medical Center

Aurora, Illinois, United States

Site Status

Saint Joseph Medical Center

Bloomington, Illinois, United States

Site Status

Graham Hospital Association

Canton, Illinois, United States

Site Status

Memorial Hospital

Carthage, Illinois, United States

Site Status

Heartland Cancer Research NCORP

Decatur, Illinois, United States

Site Status

Eureka Hospital

Eureka, Illinois, United States

Site Status

Galesburg Cottage Hospital

Galesburg, Illinois, United States

Site Status

Illinois CancerCare-Galesburg

Galesburg, Illinois, United States

Site Status

Western Illinois Cancer Treatment Center

Galesburg, Illinois, United States

Site Status

Mason District Hospital

Havana, Illinois, United States

Site Status

Hopedale Medical Complex - Hospital

Hopedale, Illinois, United States

Site Status

Joliet Oncology-Hematology Associates Limited

Joliet, Illinois, United States

Site Status

Kewanee Hospital

Kewanee, Illinois, United States

Site Status

Mcdonough District Hospital

Macomb, Illinois, United States

Site Status

Bromenn Regional Medical Center

Normal, Illinois, United States

Site Status

Community Cancer Center Foundation

Normal, Illinois, United States

Site Status

Illinois CancerCare-Ottawa Clinic

Ottawa, Illinois, United States

Site Status

Ottawa Regional Hospital and Healthcare Center

Ottawa, Illinois, United States

Site Status

OSF Saint Francis Radiation Oncology at Pekin Cancer Treatment Center

Pekin, Illinois, United States

Site Status

Pekin Hospital

Pekin, Illinois, United States

Site Status

Methodist Medical Center of Illinois

Peoria, Illinois, United States

Site Status

Proctor Hospital

Peoria, Illinois, United States

Site Status

Illinois CancerCare-Peoria

Peoria, Illinois, United States

Site Status

OSF Saint Francis Radiation Oncology at Peoria Cancer Center

Peoria, Illinois, United States

Site Status

OSF Saint Francis Medical Center

Peoria, Illinois, United States

Site Status

Illinois Valley Hospital

Peru, Illinois, United States

Site Status

Valley Radiation Oncology

Peru, Illinois, United States

Site Status

Perry Memorial Hospital

Princeton, Illinois, United States

Site Status

Saint Margaret's Hospital

Spring Valley, Illinois, United States

Site Status

Franciscan Saint Margaret Health-Hammond Campus

Hammond, Indiana, United States

Site Status

Indiana University/Melvin and Bren Simon Cancer Center

Indianapolis, Indiana, United States

Site Status

Franciscan Saint Anthony Health-Michigan City

Michigan City, Indiana, United States

Site Status

University of Maryland/Greenebaum Cancer Center

Baltimore, Maryland, United States

Site Status

Michigan Cancer Research Consortium NCORP

Ann Arbor, Michigan, United States

Site Status

Saint Joseph Mercy Hospital

Ann Arbor, Michigan, United States

Site Status

Beaumont Hospital-Dearborn

Dearborn, Michigan, United States

Site Status

Saint John Hospital and Medical Center

Detroit, Michigan, United States

Site Status

Hurley Medical Center

Flint, Michigan, United States

Site Status

Genesys Regional Medical Center-West Flint Campus

Flint, Michigan, United States

Site Status

McLaren Cancer Institute-Flint

Flint, Michigan, United States

Site Status

Allegiance Health

Jackson, Michigan, United States

Site Status

Sparrow Hospital

Lansing, Michigan, United States

Site Status

Saint Mary Mercy Hospital

Livonia, Michigan, United States

Site Status

Saint Joseph Mercy Oakland

Pontiac, Michigan, United States

Site Status

Lake Huron Medical Center

Port Huron, Michigan, United States

Site Status

Saint Mary's of Michigan

Saginaw, Michigan, United States

Site Status

Saint John Macomb-Oakland Hospital

Warren, Michigan, United States

Site Status

Mercy Hospital-Joplin

Joplin, Missouri, United States

Site Status

CHI Health Good Samaritan

Kearney, Nebraska, United States

Site Status

John F Kennedy Medical Center

Edison, New Jersey, United States

Site Status

Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital

New Brunswick, New Jersey, United States

Site Status

Rutgers New Jersey Medical School

Newark, New Jersey, United States

Site Status

Duke Women's Cancer Care Raleigh

Raleigh, North Carolina, United States

Site Status

Rex Cancer Center

Raleigh, North Carolina, United States

Site Status

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, United States

Site Status

Bryn Mawr Hospital

Bryn Mawr, Pennsylvania, United States

Site Status

Paoli Memorial Hospital

Paoli, Pennsylvania, United States

Site Status

Fox Chase Cancer Center

Philadelphia, Pennsylvania, United States

Site Status

Temple University Hospital

Philadelphia, Pennsylvania, United States

Site Status

Reading Hospital

West Reading, Pennsylvania, United States

Site Status

Lankenau Medical Center

Wynnewood, Pennsylvania, United States

Site Status

Main Line Health NCORP

Wynnewood, Pennsylvania, United States

Site Status

Audie L Murphy Veterans Affairs Hospital

San Antonio, Texas, United States

Site Status

Cancer Therapy and Research Center at The UT Health Science Center at San Antonio

San Antonio, Texas, United States

Site Status

University Hospital

San Antonio, Texas, United States

Site Status

University of Texas Health Science Center at San Antonio

San Antonio, Texas, United States

Site Status

American Fork Hospital / Huntsman Intermountain Cancer Center

American Fork, Utah, United States

Site Status

Sandra L Maxwell Cancer Center

Cedar City, Utah, United States

Site Status

Cottonwood Hospital Medical Center

Murray, Utah, United States

Site Status

Intermountain Medical Center

Murray, Utah, United States

Site Status

McKay-Dee Hospital Center

Ogden, Utah, United States

Site Status

Utah Valley Regional Medical Center

Provo, Utah, United States

Site Status

Intermountain Health Care

Salt Lake City, Utah, United States

Site Status

Utah Cancer Specialists-Salt Lake City

Salt Lake City, Utah, United States

Site Status

LDS Hospital

Salt Lake City, Utah, United States

Site Status

Dixie Medical Center Regional Cancer Center

St. George, Utah, United States

Site Status

University of Washington Medical Center

Seattle, Washington, United States

Site Status

Wheeling Hospital/Schiffler Cancer Center

Wheeling, West Virginia, United States

Site Status

University of Wisconsin Hospital and Clinics

Madison, Wisconsin, United States

Site Status

Froedtert and the Medical College of Wisconsin

Milwaukee, Wisconsin, United States

Site Status

Countries

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United States

References

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Brachman DG, Pugh SL, Ashby LS, Thomas TA, Dunbar EM, Narayan S, Robins HI, Bovi JA, Rockhill JK, Won M, Curran WP. Phase 1/2 trials of Temozolomide, Motexafin Gadolinium, and 60-Gy fractionated radiation for newly diagnosed supratentorial glioblastoma multiforme: final results of RTOG 0513. Int J Radiat Oncol Biol Phys. 2015 Apr 1;91(5):961-7. doi: 10.1016/j.ijrobp.2014.12.050.

Reference Type RESULT
PMID: 25832688 (View on PubMed)

Other Identifiers

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NCI-2009-01092

Identifier Type: REGISTRY

Identifier Source: secondary_id

CDR0000467802

Identifier Type: -

Identifier Source: secondary_id

RTOG 0513

Identifier Type: OTHER

Identifier Source: secondary_id

RTOG-0513

Identifier Type: OTHER

Identifier Source: secondary_id

U10CA021661

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NCI-2009-01092

Identifier Type: -

Identifier Source: org_study_id

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