Temozolomide & RT Followed by Dose Dense vs Temozolomide & Retinoic Acid in Pts w/Glioblastoma

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
Schering-Plough
Columbia University
Dana-Farber Cancer Institute
Information provided by (Responsible Party):
Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier:
NCT00200161
First received: September 12, 2005
Last updated: November 21, 2013
Last verified: November 2013
  Purpose

Patients have a newly diagnosed brain tumor called a malignant glioma and participate in the study to see if it is possible to increase the benefit of temozolomide when given after radiation. A recent study showed that patients with newly diagnosed glioblastoma lived longer when treated with both temozolomide and radiotherapy followed by 6 months of temozolomide than patients treated with radiotherapy alone. Patients will receive standard low dose temozolomide during radiation. After radiation, they will be randomized to receive either more intense temozolomide or continuous low dose temozolomide.


Condition Intervention Phase
Glioblastoma
Gliomas
Drug: Temozolomide
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Randomized Phase II Trial of Concurrent Temozolomide and Radiotherapy Followed by Dose Dense Versus Metronomic Temozolomide and Maintenance Cis-Retinoic Acid for Patients With Newly Diagnosed Glioblastoma and Other Malignant Gliomas

Resource links provided by NLM:


Further study details as provided by Memorial Sloan-Kettering Cancer Center:

Primary Outcome Measures:
  • To determine the overall survival of patients with newly diagnosed glioblastoma multiforme treated with concurrent temozolomide and radiotherapy followed by dose dense or metronomic dosing of temozolomide and maintenance cis-retinoic acid. [ Time Frame: until death or date of last follow up ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Progression free survival [ Time Frame: until tumor progression ] [ Designated as safety issue: No ]
  • To evaluate the prognostic impact of methylated MGMT status. [ Time Frame: at the end of study ] [ Designated as safety issue: No ]
  • To collect preliminary data on the efficacy of this regimen and impact of MGMT status in other malignant glioma subtypes. [ Time Frame: at the end of study ] [ Designated as safety issue: No ]

Estimated Enrollment: 140
Study Start Date: August 2005
Estimated Study Completion Date: August 2014
Estimated Primary Completion Date: August 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 1
Concurrent temozolomide and radiotherapy plus lose dose of temozolomide
Drug: Temozolomide
Focal RT 6000 cGy/ Temozolomide 75 mg/m2 then Temozolomide 50mg/m2 will be given to patients on days 1-28 of each 28 day cycle. Maintenance cis-retinoic acid. This therapy will start at the completion of 6 cycles of adjuvant temozolomide in all patients who have had no clinical or radiographic evidence of tumor progression.Treatment will continue in 28 day cycles until tumor progression.
Experimental: 2
Concurrent temozolomide and radiotherapy plus high dose of temozolomide
Drug: Temozolomide
Focal RT 6000 cGy/ Temozolomide 75 mg/m2 plus Temozolomide 150 mg/m2 will be given to patients on days 1-7 and 15-21 of each 28 day cycle. Maintenance cis-retinoic acid. This therapy will start at the completion of 6 cycles of adjuvant temozolomide in all patients who have had no clinical or radiographic evidence of tumor progression.Treatment will continue in 28 day cycles until tumor progression.

Detailed Description:

This is a randomized phase II study that will test two different adjuvant temozolomide regimens in patients with newly diagnosed glioblastoma multiforme. The goal of this study is to identify a regimen that would be appropriate to bring to a phase III trial and compare to the standard dosing regimen of temozolomide recently reported by Stupp et al. in the New England Journal of Medicine. Secondary goals of this study include: prospective analysis of the prognostic impact of MGMT status and generation of preliminary data regarding this treatment strategy for other types of malignant glioma.

The decision regarding which treatment patients receive is made randomly. Neither them or their doctor can select which treatment the patient will receive. There is reason to believe that both of these doses may benefit treating your brain tumor. After 6 months of chemotherapy, and assuming the brain tumor has not shown any sign of growth, they will begin receiving cis-retinoic acid. Cis retinoic acid has been shown in one study to possibly prevent or delay tumor recurrence.

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Pathologic evidence of a malignant glioma.
  • Tissue block or unstained slides must be available for MGMT analysis.
  • Age 18-70
  • KPS > 50
  • Granulocyte count >1.5 X 109/L
  • Platelet count >99 X 109/L
  • SGOT < 2.5X upper limit of normal (ULN).
  • Serum creatinine < 2X ULN.
  • Bilirubin < 2X ULN.
  • All patients must sign written informed consent.

Exclusion Criteria:

  • Any prior chemotherapy, radiotherapy and biologic therapy for glioma.
  • Any prior experimental therapy for glioma.
  • Other concurrent active malignancy (with the exception of cervical carcinoma in situ or basal cell ca of the skin).
  • Serious medical or psychiatric illness that would in the opinion of the investigator would interfere with the prescribed treatment.
  • Pregnant or breast feeding women.
  • Refusal to use effective contraception.
  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: NCT00200161

Locations
United States, New Jersey
Memorial Sloan-Kettering at Basking Ridge
Basking Ridge, New Jersey, United States, 07920
United States, New York
Memorial Sloan-Kettering Cancer Center at Commack
Commack, New York, United States, 11725
Memorial Sloan-Kettering Cancer Center
New York, New York, United States, 10021
Sponsors and Collaborators
Memorial Sloan-Kettering Cancer Center
Schering-Plough
Columbia University
Dana-Farber Cancer Institute
Investigators
Principal Investigator: Lisa DeAngelis, M.D Memorial Sloan-Kettering Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier: NCT00200161     History of Changes
Other Study ID Numbers: 05-079
Study First Received: September 12, 2005
Last Updated: November 21, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Glioblastoma
Glioma
Astrocytoma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Isotretinoin
Tretinoin
Temozolomide
Dacarbazine
Dermatologic Agents
Therapeutic Uses
Pharmacologic Actions
Antineoplastic Agents
Keratolytic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on July 23, 2014