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Motexafin Gadolinium, Temozolomide, and Radiation Therapy in Treating Patients With Newly Diagnosed Glioblastoma Multiforme or Gliosarcoma
This study is ongoing, but not recruiting participants.
First Received: March 21, 2006   Last Updated: July 21, 2009   History of Changes
Sponsors and Collaborators: Radiation Therapy Oncology Group
National Cancer Institute (NCI)
Information provided by: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00305864
  Purpose

RATIONALE: 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.

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.


Condition Intervention Phase
Brain and Central Nervous System Tumors
Drug: motexafin gadolinium
Drug: temozolomide
Procedure: adjuvant therapy
Radiation: radiation therapy
Phase I
Phase II

Study Type: Interventional
Study Design: 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 (Phase I) [ Designated as safety issue: Yes ]
  • Overall survival (Phase II) [ Designated as safety issue: No ]
  • Short- and long-term adverse effects (Phase II) [ Designated as safety issue: Yes ]
  • Progression-free survival (Phase II) [ Designated as safety issue: No ]

Estimated Enrollment: 113
Study Start Date: February 2006
Estimated Primary Completion Date: July 2009 (Final data collection date for primary outcome measure)
Detailed Description:

OBJECTIVES:

  • 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.

(Phase I)

  • Estimate the overall survival of patients treated with concurrent radiotherapy, temozolomide, and MGd followed by post-radiation temozolomide. (Phase II)
  • Determine the short- and long-term adverse effects in patients treated with this treatment. (Phase II)
  • Estimate the progression-free survival of patients with newly diagnosed supratentorial GBM or gliosarcoma treated with this regimen. (Phase II)

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.

PROJECTED ACCRUAL: A total of 113 patients will be accrued for this study.

  Eligibility

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

DISEASE CHARACTERISTICS:

  • 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

PATIENT CHARACTERISTICS:

  • 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

PRIOR CONCURRENT THERAPY:

  • See Disease Characteristics
  • 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)
  • No other concurrent chemotherapy
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00305864

  Show 103 Study Locations
Sponsors and Collaborators
Radiation Therapy Oncology Group
Investigators
Study Chair: David G. Brachman, MD, FACRO Arizona Oncology Services Foundation
Investigator: Lynn S. Ashby, MD Barrow Neurological Institute at St. Joseph's Hospital and Medical Center
  More Information

Additional Information:
No publications provided

Responsible Party: Radiation Therapy Oncology Group ( Walter John Curran, Jr )
Study ID Numbers: CDR0000467802, RTOG-0513
Study First Received: March 21, 2006
Last Updated: July 21, 2009
ClinicalTrials.gov Identifier: NCT00305864     History of Changes
Health Authority: United States: Food and Drug Administration

Keywords provided by National Cancer Institute (NCI):
adult glioblastoma
adult giant cell glioblastoma
adult gliosarcoma

Study placed in the following topic categories:
Glioblastoma
Astrocytoma
Adjuvants, Immunologic
Central Nervous System Neoplasms
Motexafin gadolinium
Temozolomide
Neuroectodermal Tumors
Photosensitizing Agents
Radiation-Sensitizing Agents
Neoplasms, Germ Cell and Embryonal
Neuroepithelioma
Antineoplastic Agents, Alkylating
Glioma
Glioblastoma Multiforme
Gliosarcoma
Alkylating Agents
Nervous System Neoplasms
Neoplasms, Glandular and Epithelial

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

ClinicalTrials.gov processed this record on August 24, 2009