Know Cancer

or
forgot password

A PHASE I/II TRIAL OF TEMOZOLOMIDE, MOTEXAFIN GADOLINIUM, AND 60 GY FRACTIONATED RADIATION FOR NEWLY DIAGNOSED SUPRATENTORIAL GLIOBLASTOMA MULTIFORME


Phase 1/Phase 2
18 Years
N/A
Not Enrolling
Both
Adult Giant Cell Glioblastoma, Adult Glioblastoma, Adult Gliosarcoma

Thank you

Trial Information

A PHASE I/II TRIAL OF TEMOZOLOMIDE, MOTEXAFIN GADOLINIUM, AND 60 GY FRACTIONATED RADIATION FOR NEWLY DIAGNOSED SUPRATENTORIAL GLIOBLASTOMA MULTIFORME


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.


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)

Type of Study:

Interventional

Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Maximum Tolerated Dose of MGd (Phase I)

Outcome Description:

Patients were to be followed for a minimum of 90 days from the start of radiation therapy (RT) and carefully evaluated with respect to treatment morbidity. A dose limiting toxicity (DLT) was defined as a grade 4 neurologic adverse event (AE) considered to be related to treatment occurring within 21 days of the conclusion of RT. For each dose level, up to seven patients were to be accrued to assure that there would be six eligible for treatment adverse event evaluation. A dose level of MGd was considered acceptable if no more than 1 patient of the 6 experience a DLT. If the current level was considered acceptable, then dose escalation occurred. Otherwise, the preceding dose level would be declared the MTD. The MTD would be used for the Phase II arm. Rating scale: 0 = not the MTD, 1 = MTD

Outcome Time Frame:

From start of radiation therapy to 90 days,

Safety Issue:

Yes

Principal Investigator

David Brachman

Investigator Role:

Principal Investigator

Investigator Affiliation:

Radiation Therapy Oncology Group

Authority:

United States: Food and Drug Administration

Study ID:

NCI-2009-01092

NCT ID:

NCT00305864

Start Date:

February 2006

Completion Date:

Related Keywords:

  • Adult Giant Cell Glioblastoma
  • Adult Glioblastoma
  • Adult Gliosarcoma
  • Glioblastoma
  • Gliosarcoma

Name

Location

Fox Chase Cancer CenterPhiladelphia, Pennsylvania  19111
University of Washington Medical CenterSeattle, Washington  98195-6043
Hurley Medical CenterFlint, Michigan  48503
University of Texas Health Science Center at San AntonioSan Antonio, Texas  78284-7811
University of Florida Health Science CenterGainesville, Florida  32610-0296
Methodist Medical Center of IllinoisPeoria, Illinois  61636
Reading Hospital and Medical CenterReading, Pennsylvania  19612-6052
LDS HospitalSalt Lake City, Utah  84143
University of Oklahoma Health Sciences CenterOklahoma City, Oklahoma  73104
Mobile Infirmary Medical CenterMobile, Alabama  36640-0460
University of Wisconsin Hospital and ClinicsMadison, Wisconsin  53792-0001
American Fork HospitalAmerican Fork, Utah  84003
Cottonwood Hospital Medical CenterMurray, Utah  84107
McKay-Dee Hospital CenterOgden, Utah  84403
Paoli Memorial HospitalPaoli, Pennsylvania  19301-1792
Saint Rose HospitalHayward, California  94545
Alta Bates Summit Medical Center - Summit CampusOakland, California  94609
Memorial HospitalCarthage, Illinois  62321
Galesburg Cottage HospitalGalesburg, Illinois  61401
Galesburg ClinicGalesburg, Illinois  61401
Mason District HospitalHavana, Illinois  62644
Kewanee HospitalKewanee, Illinois  61443
McDonough District HospitalMacomb, Illinois  61455
BroMenn Regional Medical CenterNormal, Illinois  61761
Proctor HospitalPeoria, Illinois  61614
Perry Memorial HospitalPrinceton, Illinois  61356
Valley Cancer CenterSpring Valley, Illinois  61362
Bryn Mawr HospitalBryn Mawr, Pennsylvania  19010
Eureka HospitalEureka, Illinois  61530
Graham Hospital AssociationCanton, Illinois  61520
Saint Joseph Medical CenterJoliet, Illinois  60435
Pekin HospitalPekin, Illinois  61554
Saint Joseph Mercy HospitalAnn Arbor, Michigan  48106
Highland General HospitalOakland, California  94602
Temple University HospitalPhiladelphia, Pennsylvania  19140
Arizona Oncology Services FoundationPhoenix, Arizona  85013
Bay Area Tumor InstituteOakland, California  94609
East Bay Radiation Oncology CenterCastro Valley, California  94546
Contra Costa Regional Medical CenterMartinez, California  94553-3156
Larry G Strieff MD Medical CorporationOakland, California  94609
University of FloridaGainesville, Florida  32610-0277
El Camino HospitalMountain View, California  94040
University of Arizona Health Sciences CenterTucson, Arizona  85724
Indiana University Medical CenterIndianapolis, Indiana  46202
Lankenau HospitalWynnewood, Pennsylvania  19096
University of Southern CaliforniaLos Angeles, California  90033
Froedtert and the Medical College of WisconsinMilwaukee, Wisconsin  53226
OSF Saint Francis Medical CenterPeoria, Illinois  61637
Valley Medical Oncology Consultants-Castro ValleyCastro Valley, California  94546
Eden Hospital Medical CenterCastro Valley, California  94546
Valley Medical Oncology Consultants-FremontFremont, California  94538
Bay Area Breast Surgeons IncOakland, California  94609
Tom K Lee IncOakland, California  94609
Valley Medical Oncology ConsultantsPleasanton, California  94588
Valley Care Health System - PleasantonPleasanton, California  94588
Doctors Medical Center- JC Robinson Regional Cancer CenterSan Pablo, California  94806
Rush - Copley Medical CenterAurora, Illinois  60504
Intercommunity Cancer CenterGalesburg, Illinois  61401
Hopedale Medical Complex - HospitalHopedale, Illinois  61747
Joliet Oncology-Hematology Associates LimitedJoliet, Illinois  60435
Community Cancer Center FoundationNormal, Illinois  61761
Illinois CancerCare-Ottawa ClinicOttawa, Illinois  61350
Ottawa Regional Hospital and Healthcare CenterOttawa, Illinois  61350
Pekin Cancer Treatment CenterPekin, Illinois  61554
Illinois Oncology Research Association CCOPPeoria, Illinois  61615
Illinois CancerCare-PeoriaPeoria, Illinois  61615
Illinois Valley HospitalPeru, Illinois  61354
Saint Margaret's HospitalSpring Valley, Illinois  61362
Carle Clinic-Urbana MainUrbana, Illinois  61801
Saint Anthony Memorial Health CenterMichigan City, Indiana  46360
Michigan Cancer Research Consortium Community Clinical Oncology ProgramAnn Arbor, Michigan  48106
Oakwood HospitalDearborn, Michigan  48123
Saint John Hospital and Medical CenterDetroit, Michigan  48236
McLaren Regional Medical CenterFlint, Michigan  48532
Allegiance HealthJackson, Michigan  49201
Sparrow HospitalLansing, Michigan  48912
Saint Mary Mercy HospitalLivonia, Michigan  48154
Saint Joseph Mercy OaklandPontiac, Michigan  48341-2985
Saint Joseph Mercy Port HuronPort Huron, Michigan  48060
Saint Mary's of MichiganSaginaw, Michigan  48601
Saint John Macomb-Oakland HospitalWarren, Michigan  48093
Saint John's Regional Medical CenterJoplin, Missouri  64804
Good Samaritan HospitalKearney, Nebraska  68847
Mainline Health CCOPWynnewood, Pennsylvania  19096
Audie L Murphy Veterans Affairs HospitalSan Antonio, Texas  78209
University HospitalSan Antonio, Texas  78229
Wheeling HospitalWheeling, West Virginia  26003
University of Maryland Greenebaum Cancer CenterBaltimore, Maryland  21201
Denver Veterans Administration Medical CenterDenver, Colorado  80220
John F Kennedy Medical CenterEdison, New Jersey  08818
UMDNJ - New Jersey Medical SchoolNewark, New Jersey  07103
Sandra L Maxwell Cancer CenterCedar City, Utah  84720
Intermountain Medical CenterMurray, Utah  84157
Utah Valley Regional Medical CenterProvo, Utah  84603
Dixie Medical Center Regional Cancer CenterSaint George, Utah  84770
Intermountain Health CareSalt Lake City, Utah  84103
Utah Cancer Specialists-Salt Lake CitySalt Lake City, Utah  84106
University of Miami Miller School of Medicine-Sylvester Cancer CenterMiami, Florida  33136
Cancer Centers of North CarolinaRaleigh, North Carolina  27607
OSF Saint Francis Medical Center Radiation Oncology Service at the Central Illinois Comprehensive CCPeoria, Illinois  61615-7827
Rex HospitalRaleigh, North Carolina  27606
Los Angeles County-USC Medical CenterLos Angeles, California  90033
Stanford University Hospitals and ClinicsStanford, California  94305
UMDNJ - Robert Wood Johnson University HospitalNew Brunswick, New Jersey  08903
Genesys Regional Medical Center-West Flint CampusFlint, Michigan  48532
Franciscan Saint Margaret Health-Hammond CampusHammond, Indiana  46320