Carboxyamidotriazole + RT in Treating Patients Newly Diagnosed Supratentorial GBM

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00004146
First received: December 10, 1999
Last updated: May 5, 2015
Last verified: April 2015
  Purpose

Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells. Combining radiation therapy with chemotherapy may kill more tumor cells. Phase II trial to study the effectiveness of carboxyamidotriazole plus radiation therapy in treating patients who have newly diagnosed supratentorial glioblastoma multiforme.


Condition Intervention Phase
Adult Giant Cell Glioblastoma
Adult Glioblastoma
Adult Gliosarcoma
Radiation: radiation therapy
Drug: carboxyamidotriazole
Other: pharmacological study
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 II Clinical and Pharmacologic Study of Radiation Therapy and CAI (Carboxy-Amido Triazole) 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:
  • Overall Survival Rate [ Time Frame: approximately 30 months ] [ Designated as safety issue: Yes ]
    estimated period of time event assessed 30 months. event assessed from time of histological diagnosis to death

  • Toxicity of CAI When Combined With RT [ Time Frame: pts were reviewed for toxicity while on treatement - median time of 2 months ] [ Designated as safety issue: Yes ]
    patients who experienced a grade 3 or higher event considered at least possibly related to CAI

  • Correlation Between PK CAI and Toxicity in This pt Population [ Time Frame: during treatment ] [ Designated as safety issue: Yes ]
    PK paramenters including steady state CAI concentrations with toxicity/or drug activity


Enrollment: 55
Study Start Date: March 2000
Study Completion Date: January 2010
Primary Completion Date: January 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (RT and CAI)

Patients receive induction therapy consisting of radiotherapy once daily 5 days a week plus oral carboxyamidotriazole once daily for 6 weeks followed by carboxyamidotriazole alone daily for 4 weeks. Patients continue on oral carboxyamidotriazole once daily as maintenance therapy in the absence of disease progression or unacceptable toxicity. Patients are followed monthly for survival.

Other: pharmacological study, radiation therapy

Radiation: radiation therapy
Undergo radiotherapy
Other Names:
  • irradiation
  • radiotherapy
  • therapy, radiation
Drug: carboxyamidotriazole
Given orally
Other Names:
  • CAI
  • carboxyamido-triazole
  • carboxyaminoimidazole
Other: pharmacological study
Correlative studies
Other Name: pharmacological studies

Detailed Description:

PRIMARY OBJECTIVES:

I. To evaluate overall survival rate in patients administered CAI (carboxyamidotriazole) and radiation therapy to adults with newly diagnosed glioblastoma multiforme.

II. To determine the toxicity of CAI when combined with cranial irradiation. III. To estimate correlations between pharmacokinetic parameters, including steady state CAI concentration, with toxicity and/or drug activity in this patient population.

IV. To estimate duration of disease free progression with this treatment regime.

OUTLINE: This is a multicenter study.

Patients receive induction therapy consisting of radiotherapy once daily 5 days a week plus oral carboxyamidotriazole once daily for 6 weeks followed by carboxyamidotriazole alone daily for 4 weeks. Patients continue on oral carboxyamidotriazole once daily as maintenance therapy in the absence of disease progression or unacceptable toxicity. Patients are followed monthly for survival.

PROJECTED ACCRUAL: A total of 54 patients will be accrued for this study over 1.5 years.

  Eligibility

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

Inclusion Criteria:

  • Patients must have histologically confirmed supratentorial grade IV astrocytoma (glioblastoma multiforme)
  • Patients must have measurable or non-measurable tumor on the post operative, pretreatment MRI/CT scan (within two weeks of starting treatment)
  • Patients must not have received prior radiation therapy, chemotherapy, hormonal therapy, immunotherapy or therapy with biologic agents (including immunotoxins, immunoconjugates, antisense, peptide receptor antagonists, interferons, interleukins, TIL, LAK or gene therapy), or hormonal therapy for their brain tumor; glucocorticoid therapy is allowed
  • Patients must have recovered from the immediate post-operative period and be maintained on a stable steroid regimen (no increase for the last five days)
  • Absolute neutrophil count >= 1500/mm^3
  • Platelets >= 100,000/mm^3
  • Hemoglobin concentration >= 9.0 g/dl
  • Creatinine =< 1.7mg/dL
  • Total bilirubin =< 1.2 mg/dl
  • Transaminases =< 2 times above the upper limits of the institutional normal
  • Estimated life expectancy greater than 2 months
  • Patients must give informed consent and understand the investigational nature of this study and its potential risks and benefits
  • Patients, if female and of childbearing potential must have a negative serum beta-hCG test and must not be breast feeding; all patients with the potential for pregnancy should be counseled and requested to follow acceptable birth control methods to avoid conception
  • Patients must have a Karnofsky performance status of >= 60%
  • No other serious concurrent infection or other medical illness should be present which would jeopardize the ability of the patient to receive the drug outlined in this protocol with reasonable safety
  • Patients must have no concurrent malignancy except curatively treated basal or squamous cell carcinoma of the skin or carcinoma in situ; patients with prior malignancies must be disease-free for >= five years

Exclusion Criteria:

  • Patients must be able to comply with prescribed medical care
  • Prior therapy for the brain tumor (except surgery)
  • Prior treatment with antineoplastic agents, including CAI
  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: NCT00004146

Locations
United States, Alabama
University of Alabama Birmingham
Birmingham, Alabama, United States, 35294
United States, Florida
Moffitt Cancer Center
Tampa, Florida, United States, 33612
United States, Georgia
Emory University/Winship Cancer Institute
Atlanta, Georgia, United States, 30322
United States, Maryland
Johns Hopkins University
Baltimore, Maryland, United States, 21287
United States, Michigan
Henry Ford Hospital
Detroit, Michigan, United States, 48202
United States, North Carolina
Wake Forest University
Winston-Salem, North Carolina, United States, 27157
United States, Pennsylvania
University of Pennsylavania/Abramson Cancer Center
Philadelphia, Pennsylvania, United States, 19104
United States, Texas
University of Texas Health Science Center at San Antonio
San Antonio, Texas, United States, 78229
Sponsors and Collaborators
Investigators
Principal Investigator: Tom Mikkelsen, MD New Approaches to Brain Tumor Therapy Consortium
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00004146     History of Changes
Other Study ID Numbers: NCI-2012-03011, NCI-2012-03011, CDR67378, NABTT-9904, NABTT-9904, U01CA062475
Study First Received: December 10, 1999
Results First Received: March 13, 2015
Last Updated: May 5, 2015
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Glioblastoma
Gliosarcoma
Astrocytoma
Glioma
Neoplasms
Neoplasms by Histologic Type
Neoplasms, Germ Cell and Embryonal
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Carboxyamido-triazole
Antineoplastic Agents
Calcium Channel Blockers
Cardiovascular Agents
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on May 26, 2015