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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00305864
First received: March 21, 2006
Last updated: April 29, 2014
Last verified: October 2011
  Purpose

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.


Condition Intervention Phase
Adult Giant Cell Glioblastoma
Adult Glioblastoma
Adult Gliosarcoma
Radiation: 3-dimensional conformal radiation therapy
Drug: temozolomide
Drug: motexafin gadolinium
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A PHASE I/II TRIAL OF TEMOZOLOMIDE, MOTEXAFIN GADOLINIUM, AND 60 GY FRACTIONATED RADIATION FOR NEWLY DIAGNOSED SUPRATENTORIAL GLIOBLASTOMA MULTIFORME

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Maximum Tolerated Dose of MGd (Phase I) [ Time Frame: From start of radiation therapy to 90 days, ] [ Designated as safety issue: Yes ]

    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


  • Median Overall Survival (Phase II) [ Time Frame: From randomization to date of death or last follow-up. Analysis occurs after all patients have been potentially forllowed for at least 18 months. ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Progression-free Survival (Phase II) [ Time Frame: From randomization to date of progression, death, or last follow-up. Analysis occurs at the same time as the primary outcome analysis. ] [ Designated as safety issue: No ]
    Progression will be defined as a > 25% increase in tumor area.


Enrollment: 118
Study Start Date: February 2006
Study Completion Date: March 2011
Primary Completion Date: February 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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.
Radiation: 3-dimensional conformal radiation therapy
Undergo radiotherapy
Other Names:
  • 3D conformal radiation therapy
  • 3D-CRT
Drug: temozolomide
Given orally
Other Names:
  • SCH 52365
  • Temodal
  • Temodar
  • TMZ
Drug: motexafin gadolinium
Given IV
Other Names:
  • gadolinium texaphyrin
  • Gd (III) Texaphryin
  • Gd-Tex
  • PCI-0120
  • Xcytrin
Experimental: 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.
Radiation: 3-dimensional conformal radiation therapy
Undergo radiotherapy
Other Names:
  • 3D conformal radiation therapy
  • 3D-CRT
Drug: temozolomide
Given orally
Other Names:
  • SCH 52365
  • Temodal
  • Temodar
  • TMZ
Drug: motexafin gadolinium
Given IV
Other Names:
  • gadolinium texaphyrin
  • Gd (III) Texaphryin
  • Gd-Tex
  • PCI-0120
  • Xcytrin
Experimental: 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.
Radiation: 3-dimensional conformal radiation therapy
Undergo radiotherapy
Other Names:
  • 3D conformal radiation therapy
  • 3D-CRT
Drug: temozolomide
Given orally
Other Names:
  • SCH 52365
  • Temodal
  • Temodar
  • TMZ
Drug: motexafin gadolinium
Given IV
Other Names:
  • gadolinium texaphyrin
  • Gd (III) Texaphryin
  • Gd-Tex
  • PCI-0120
  • Xcytrin
Active Comparator: 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.
Radiation: 3-dimensional conformal radiation therapy
Undergo radiotherapy
Other Names:
  • 3D conformal radiation therapy
  • 3D-CRT
Drug: temozolomide
Given orally
Other Names:
  • SCH 52365
  • Temodal
  • Temodar
  • TMZ
Drug: motexafin gadolinium
Given IV
Other Names:
  • gadolinium texaphyrin
  • Gd (III) Texaphryin
  • Gd-Tex
  • PCI-0120
  • Xcytrin

Detailed 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00305864

  Show 107 Study Locations
Sponsors and Collaborators
Investigators
Principal Investigator: David Brachman Radiation Therapy Oncology Group
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00305864     History of Changes
Other Study ID Numbers: NCI-2009-01092, NCI-2009-01092, CDR0000467802, RTOG 0513, RTOG-0513, U10CA021661
Study First Received: March 21, 2006
Results First Received: March 5, 2013
Last Updated: April 29, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Glioblastoma
Gliosarcoma
Astrocytoma
Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Temozolomide
Dacarbazine
Motexafin gadolinium
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Photosensitizing Agents
Radiation-Sensitizing Agents
Physiological Effects of Drugs
Dermatologic Agents

ClinicalTrials.gov processed this record on July 28, 2014