Oxaliplatin in Treating Patients With Newly Diagnosed Glioblastoma Multiforme

This study has been terminated.
(Administratively complete.)
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00005856
First received: June 2, 2000
Last updated: January 23, 2013
Last verified: January 2013
  Purpose

This phase I/II trial is studying the side effects and best dose of oxaliplatin in treating patients with newly diagnosed glioblastoma multiforme. Drugs used in chemotherapy, such as oxaliplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing


Condition Intervention Phase
Adult Giant Cell Glioblastoma
Adult Glioblastoma
Adult Gliosarcoma
Drug: oxaliplatin
Other: pharmacological study
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: Phase I/II Trial of Oxaliplatin as Neoadjuvant Treatment in Adults With Newly Diagnosed Glioblastoma Multiforme

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Maximum-tolerated dose (MTD) defined as the dose level at which 2 out of 6 or the dose level below that at which >= 2 of 3 or > 2 of 6 patients experience dose-limiting toxicity (DLT) assessed by Common Toxicity Criteria (CTC) version 2.0 (Phase I) [ Time Frame: 14 days ] [ Designated as safety issue: Yes ]
  • DLT is defined as grade 3 or 4 nonhematological toxicities or hematological toxicities as assessed by CTC version 2.0 (Phase I) [ Time Frame: 14 days ] [ Designated as safety issue: Yes ]
  • Pharmacokinetics of oxaliplatin (Phase I) [ Time Frame: At baseline, at immediately post infusion, at 2, 4, 22, and 24 hours (of course 1) ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Response rate (Phase II) [ Time Frame: Up to 7 years ] [ Designated as safety issue: No ]
  • Duration of survival (Phase II) [ Time Frame: Up to 7 years ] [ Designated as safety issue: No ]
    Estimated with 95% confidence intervals.

  • Frequency of toxicity as assessed by CTC version 2.0 (Phase II) [ Time Frame: Up to 7 years after completion of study treatment ] [ Designated as safety issue: Yes ]
    The proportion of patients with serious or life threatening toxicities will be estimated along with 95% confidence intervals.


Enrollment: 59
Study Start Date: December 2000
Primary Completion Date: January 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (oxaliplatin)
Patients receive oxaliplatin IV over 2 hours on day 1. Treatment repeats every 14 days for a maximum of 6 courses in the absence of unacceptable toxicity or disease progression.
Drug: oxaliplatin
Given IV
Other Names:
  • 1-OHP
  • Dacotin
  • Dacplat
  • Eloxatin
  • L-OHP
Other: pharmacological study
Correlative studies
Other Name: pharmacological studies

Detailed Description:

OBJECTIVES:

I. Determine the maximum tolerated dose of oxaliplatin in patients with newly diagnosed glioblastoma multiforme who are receiving or not receiving anticonvulsants known to be metabolized by P450.

II. Determine the dose-limiting toxicity and safety profile of this drug in this patient population.

III. Assess the pharmacokinetics of this drug on this schedule and determine the effects of P450-inducing anticonvulsants on the pharmacokinetics in these patients.

IV. Determine the radiographic response rate in patients treated with this drug.

V. Determine survival and drug toxicity in these patients.

OUTLINE: This is a phase I dose-escalation study of oxaliplatin followed by a phase II study. Patients are stratified according to whether concurrent anticonvulsant drugs induce P450 (yes vs modest/no or no drugs).

Phase I: Patients receive oxaliplatin IV over 2 hours on day 1. Treatment repeats every 14 days for a maximum of 6 courses in the absence of unacceptable toxicity or disease progression.

Cohorts of 3-6 patients (per stratum) receive escalating doses of oxaliplatin until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity.

Phase II: Patients receive oxaliplatin as in phase I at the MTD determined in phase I.

Patients are followed at 1 month, every 2 months until disease progression, and then monthly thereafter.

PROJECTED ACCRUAL: Approximately 24 patients (12 per stratum) will be accrued for the phase I part of this study within 8-12 months. A total of 18-35 patients will be accrued for the phase II part of this study within 5-12 months.

  Eligibility

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

Inclusion Criteria:

  • Histologically confirmed supratentorial grade IV astrocytoma

    • Glioblastoma multiforme
  • Subtotal resection or biopsy with measurable and contrast-enhancing disease on the postoperative, pretreatment MRI/CT scan
  • Performance status - Karnofsky 60-100%
  • Absolute neutrophil count at least 1,500/mm^3
  • Platelet count at least 100,000/mm^3
  • Hemoglobin at least 9.0 g/dL
  • Bilirubin normal
  • Creatinine normal
  • Creatinine clearance at least 60 mL/min
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • No serious concurrent infection or medical illness that would jeopardize ability to receive protocol chemotherapy with reasonable safety
  • No other prior malignancy within the past 5 years except curatively treated carcinoma in situ or basal cell skin cancer
  • No grade 2 or greater pre-existing sensory neuropathy
  • No history of allergy to platinum compounds or to antiemetics appropriate for administration in conjunction with protocol chemotherapy
  • Mini mental score at least 15
  • No prior immunotherapy for glioblastoma multiforme
  • No prior biologic therapy for glioblastoma multiforme, including:

    • Immunotoxins
    • Immunoconjugates
    • Antiangiogenesis compounds
    • Antisense
    • Peptide receptor antagonists
    • Interferons
    • Interleukins
    • Tumor infiltrating lymphocytes
    • Lymphokine activated killer cells
    • Gene therapy
  • No concurrent filgrastim (G-CSF)
  • No prior chemotherapy for glioblastoma multiforme
  • No prior hormonal therapy for glioblastoma multiforme
  • Prior glucocorticoid therapy for glioblastoma multiforme allowed
  • Must be maintained on a stable (lowest required dose) corticosteroid regimen for at least 5 days before and during study
  • No concurrent dexamethasone as an antiemetic
  • No prior radiotherapy for glioblastoma multiforme
  • Recovered from immediate postoperative period
  • At least 10 days since prior anticonvulsant drug that induces hepatic metabolic enzymes
  • No other concurrent investigational agents
  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: NCT00005856

Locations
United States, Maryland
New Approaches to Brain Tumor Therapy Consortium
Baltimore, Maryland, United States, 21231-1000
Sponsors and Collaborators
Investigators
Principal Investigator: Tracy Batchelor New Approaches to Brain Tumor Therapy Consortium
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00005856     History of Changes
Other Study ID Numbers: NCI-2012-02336, 9902, U01CA062475, CDR0000067883
Study First Received: June 2, 2000
Last Updated: January 23, 2013
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
Oxaliplatin
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 29, 2014