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

Adult Glioblastoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00305864
• Other study ID #: NCI-2009-01092
• Secondary ID: NCI-2009-01092CD
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: March 21, 2006
• Last updated: February 2, 2018
• Start date: February 9, 2006
• Est. completion date: March 15, 2011

Study information

• Verified date: February 2018
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 118
• Est. completion date: March 15, 2011
• Est. primary completion date: February 16, 2011
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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)

Related Conditions & MeSH terms

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

Intervention

Radiation:
• 3-Dimensional Conformal Radiation Therapy
Undergo radiotherapy

Drug:
• Motexafin Gadolinium
Given IV
• Temozolomide
Given orally

Locations

Country	Name	City	State
United States	American Fork Hospital / Huntsman Intermountain Cancer Center	American Fork	Utah
United States	Michigan Cancer Research Consortium NCORP	Ann Arbor	Michigan
United States	Saint Joseph Mercy Hospital	Ann Arbor	Michigan
United States	Rush - Copley Medical Center	Aurora	Illinois
United States	University of Maryland/Greenebaum Cancer Center	Baltimore	Maryland
United States	Saint Joseph Medical Center	Bloomington	Illinois
United States	Bryn Mawr Hospital	Bryn Mawr	Pennsylvania
United States	Graham Hospital Association	Canton	Illinois
United States	Memorial Hospital	Carthage	Illinois
United States	East Bay Radiation Oncology Center	Castro Valley	California
United States	Eden Hospital Medical Center	Castro Valley	California
United States	Valley Medical Oncology Consultants-Castro Valley	Castro Valley	California
United States	Sandra L Maxwell Cancer Center	Cedar City	Utah
United States	Beaumont Hospital-Dearborn	Dearborn	Michigan
United States	Heartland Cancer Research NCORP	Decatur	Illinois
United States	Denver Veterans Administration Medical Center	Denver	Colorado
United States	Saint John Hospital and Medical Center	Detroit	Michigan
United States	John F Kennedy Medical Center	Edison	New Jersey
United States	Bay Area Breast Surgeons Inc	Emeryville	California
United States	Eureka Hospital	Eureka	Illinois
United States	Genesys Regional Medical Center-West Flint Campus	Flint	Michigan
United States	Hurley Medical Center	Flint	Michigan
United States	McLaren Cancer Institute-Flint	Flint	Michigan
United States	Valley Medical Oncology Consultants-Fremont	Fremont	California
United States	University of Florida Health Science Center - Gainesville	Gainesville	Florida
United States	Galesburg Cottage Hospital	Galesburg	Illinois
United States	Illinois CancerCare-Galesburg	Galesburg	Illinois
United States	Western Illinois Cancer Treatment Center	Galesburg	Illinois
United States	Franciscan Saint Margaret Health-Hammond Campus	Hammond	Indiana
United States	Mason District Hospital	Havana	Illinois
United States	Saint Rose Hospital	Hayward	California
United States	Hopedale Medical Complex - Hospital	Hopedale	Illinois
United States	Indiana University/Melvin and Bren Simon Cancer Center	Indianapolis	Indiana
United States	Allegiance Health	Jackson	Michigan
United States	University of Florida Health Science Center - Jacksonville	Jacksonville	Florida
United States	Joliet Oncology-Hematology Associates Limited	Joliet	Illinois
United States	Mercy Hospital-Joplin	Joplin	Missouri
United States	CHI Health Good Samaritan	Kearney	Nebraska
United States	Kewanee Hospital	Kewanee	Illinois
United States	Sparrow Hospital	Lansing	Michigan
United States	Saint Mary Mercy Hospital	Livonia	Michigan
United States	Los Angeles County-USC Medical Center	Los Angeles	California
United States	USC / Norris Comprehensive Cancer Center	Los Angeles	California
United States	Mcdonough District Hospital	Macomb	Illinois
United States	University of Wisconsin Hospital and Clinics	Madison	Wisconsin
United States	Contra Costa Regional Medical Center	Martinez	California
United States	University of Miami Miller School of Medicine-Sylvester Cancer Center	Miami	Florida
United States	Franciscan Saint Anthony Health-Michigan City	Michigan City	Indiana
United States	Froedtert and the Medical College of Wisconsin	Milwaukee	Wisconsin
United States	Mobile Infirmary Medical Center	Mobile	Alabama
United States	El Camino Hospital	Mountain View	California
United States	Cottonwood Hospital Medical Center	Murray	Utah
United States	Intermountain Medical Center	Murray	Utah
United States	Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital	New Brunswick	New Jersey
United States	Rutgers New Jersey Medical School	Newark	New Jersey
United States	Bromenn Regional Medical Center	Normal	Illinois
United States	Community Cancer Center Foundation	Normal	Illinois
United States	Alta Bates Summit Medical Center - Summit Campus	Oakland	California
United States	Bay Area Tumor Institute	Oakland	California
United States	Hematology and Oncology Associates-Oakland	Oakland	California
United States	Highland General Hospital	Oakland	California
United States	Tom K Lee Inc	Oakland	California
United States	McKay-Dee Hospital Center	Ogden	Utah
United States	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma
United States	Illinois CancerCare-Ottawa Clinic	Ottawa	Illinois
United States	Ottawa Regional Hospital and Healthcare Center	Ottawa	Illinois
United States	Stanford Cancer Institute Palo Alto	Palo Alto	California
United States	Paoli Memorial Hospital	Paoli	Pennsylvania
United States	OSF Saint Francis Radiation Oncology at Pekin Cancer Treatment Center	Pekin	Illinois
United States	Pekin Hospital	Pekin	Illinois
United States	Illinois CancerCare-Peoria	Peoria	Illinois
United States	Methodist Medical Center of Illinois	Peoria	Illinois
United States	OSF Saint Francis Medical Center	Peoria	Illinois
United States	OSF Saint Francis Radiation Oncology at Peoria Cancer Center	Peoria	Illinois
United States	Proctor Hospital	Peoria	Illinois
United States	Illinois Valley Hospital	Peru	Illinois
United States	Valley Radiation Oncology	Peru	Illinois
United States	Fox Chase Cancer Center	Philadelphia	Pennsylvania
United States	Temple University Hospital	Philadelphia	Pennsylvania
United States	Valley Care Health System - Pleasanton	Pleasanton	California
United States	Valley Medical Oncology Consultants	Pleasanton	California
United States	Saint Joseph Mercy Oakland	Pontiac	Michigan
United States	Lake Huron Medical Center	Port Huron	Michigan
United States	Perry Memorial Hospital	Princeton	Illinois
United States	Utah Valley Regional Medical Center	Provo	Utah
United States	Duke Women's Cancer Care Raleigh	Raleigh	North Carolina
United States	Rex Cancer Center	Raleigh	North Carolina
United States	Saint Mary's of Michigan	Saginaw	Michigan
United States	Dixie Medical Center Regional Cancer Center	Saint George	Utah
United States	Intermountain Health Care	Salt Lake City	Utah
United States	LDS Hospital	Salt Lake City	Utah
United States	Utah Cancer Specialists-Salt Lake City	Salt Lake City	Utah
United States	Audie L Murphy Veterans Affairs Hospital	San Antonio	Texas
United States	Cancer Therapy and Research Center at The UT Health Science Center at San Antonio	San Antonio	Texas
United States	University Hospital	San Antonio	Texas
United States	University of Texas Health Science Center at San Antonio	San Antonio	Texas
United States	Doctors Medical Center- JC Robinson Regional Cancer Center	San Pablo	California
United States	Arizona Oncology Services Foundation	Scottsdale	Arizona
United States	University of Washington Medical Center	Seattle	Washington
United States	Saint Margaret's Hospital	Spring Valley	Illinois
United States	The University of Arizona Medical Center-University Campus	Tucson	Arizona
United States	Saint John Macomb-Oakland Hospital	Warren	Michigan
United States	Reading Hospital	West Reading	Pennsylvania
United States	Wheeling Hospital/Schiffler Cancer Center	Wheeling	West Virginia
United States	Lankenau Medical Center	Wynnewood	Pennsylvania
United States	Main Line Health NCORP	Wynnewood	Pennsylvania

Sponsors (2)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)	Radiation Therapy Oncology Group

Country where clinical trial is conducted

United States, 

References & Publications (1)

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 mu — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum Tolerated Dose of MGd (Phase I)	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 maximum tolerated dose (MTD). The MTD would be used for the Phase II arm.; Rating scale: 0 = not the MTD, 1 = MTD	From start of radiation therapy to 90 days,
Primary	Median Overall Survival (Phase II)	Survival time was defined as the time from baseline to date of death from any cause. Patients last known to be alive are censored at date of last contact.	From randomization to date of death or last follow-up. Analysis occurs after all patients have been potentially followed for at least 18 months. Patients were followed up to 54.3 months
Secondary	Progression-free Survival (Phase II)	Progression will be defined as a > 25% increase in tumor area. Progression-free survival time was defined as the time from baseline to date of death from any cause. Patients last known to be alive are censored at date of last contact.	From randomization to date of progression, death, or last follow-up. Analysis occurs after all patients have been potentially followed for at least 18 months. Patients were followed up to 54.3 months.