Carboxyamidotriazole + RT in Treating Patients Newly Diagnosed Supratentorial GBM

Phase II Clinical and Pharmacologic Study of Radiation Therapy and CAI (Carboxy-Amido Triazole) in Adults With Newly Diagnosed Glioblastoma Multiforme

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.

Study Overview

• Status: Completed
• Conditions: Adult Giant Cell Glioblastoma; Adult Glioblastoma; Adult Gliosarcoma
• Intervention / Treatment: Other: pharmacological study; Radiation: radiation therapy; Drug: carboxyamidotriazole

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.

• Study Type: Interventional
• Enrollment (Actual): 55
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • University of Alabama Birmingham
  • Florida
    • Tampa, Florida, United States, 33612
      • Moffitt Cancer Center
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University/Winship Cancer Institute
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins University
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Henry Ford Hospital
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest University
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylavania/Abramson Cancer Center
  • Texas
    • San Antonio, Texas, United States, 78229
      • University of Texas Health Science Center at San Antonio

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

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

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival Rate	estimated period of time event assessed 30 months. event assessed from time of histological diagnosis to death	approximately 30 months
Toxicity of CAI When Combined With RT	patients who experienced a grade 3 or higher event considered at least possibly related to CAI	pts were reviewed for toxicity while on treatement - median time of 2 months
Correlation Between PK CAI and Toxicity in This pt Population	PK paramenters including steady state CAI concentrations with toxicity/or drug activity	during treatment

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Tom Mikkelsen, MD, New Approaches to Brain Tumor Therapy Consortium

Study record dates

Study Major Dates

• Study Start: March 1, 2000
• Primary Completion (Actual): January 1, 2010
• Study Completion (Actual): January 1, 2010

Study Registration Dates

• First Submitted: December 10, 1999
• First Submitted That Met QC Criteria: June 3, 2004
• First Posted (Estimate): June 4, 2004

Study Record Updates

• Last Update Posted (Estimate): May 8, 2015
• Last Update Submitted That Met QC Criteria: May 5, 2015
• Last Verified: April 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Glioblastoma; Gliosarcoma; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Membrane Transport Modulators; Calcium-Regulating Hormones and Agents; Calcium Channel Blockers; Carboxyamido-triazole
• Other Study ID Numbers: NCI-2012-03011 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); U01CA062475 (U.S. NIH Grant/Contract); CDR67378; NABTT-9904 (Other Identifier: CTEP)