Carboxyamidotriazole + RT in Treating Patients Newly Diagnosed Supratentorial GBM

Adult Glioblastoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00004146
• Other study ID #: NCI-2012-03011
• Secondary ID: NCI-2012-03011CD
• Status: Completed
• Phase: Phase 2
• First received: December 10, 1999
• Last updated: May 5, 2015
• Start date: March 2000
• Est. completion date: January 2010

Study information

• Verified date: April 2015
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 55
• Est. completion date: January 2010
• Est. primary completion date: January 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Adult Giant Cell Glioblastoma
• Adult Glioblastoma
• Adult Gliosarcoma
• Glioblastoma
• Gliosarcoma

Intervention

Radiation:
• radiation therapy
Undergo radiotherapy

Drug:
• carboxyamidotriazole
Given orally

Other:
• pharmacological study
Correlative studies

Locations

Country	Name	City	State
United States	Emory University/Winship Cancer Institute	Atlanta	Georgia
United States	Johns Hopkins University	Baltimore	Maryland
United States	University of Alabama Birmingham	Birmingham	Alabama
United States	Henry Ford Hospital	Detroit	Michigan
United States	University of Pennsylavania/Abramson Cancer Center	Philadelphia	Pennsylvania
United States	University of Texas Health Science Center at San Antonio	San Antonio	Texas
United States	Moffitt Cancer Center	Tampa	Florida
United States	Wake Forest University	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Survival Rate	estimated period of time event assessed 30 months. event assessed from time of histological diagnosis to death	approximately 30 months	Yes
Primary	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	Yes
Primary	Correlation Between PK CAI and Toxicity in This pt Population	PK paramenters including steady state CAI concentrations with toxicity/or drug activity	during treatment	Yes