Carboxyamidotriazole + RT in Treating Patients Newly Diagnosed Supratentorial GBM

Phase 2

Completed

• Conditions: Adult Giant Cell Glioblastoma; Adult Glioblastoma; Adult Gliosarcoma
• Interventions: Radiation: radiation therapy; Drug: carboxyamidotriazole; Other: pharmacological study

• Registration Number: NCT00004146
• Lead Sponsor: National Cancer Institute (NCI)

Brief 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.

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 Timeline

• Study First Submitted: 1999-12-10
• Study Start: 2000-03
• Study First Submitted QC: 2004-06-03
• Study First Posted: 2004-06-04
• Primary Completion: 2010-01
• Study Completion: 2010-01
• Results First Submitted: 2015-03-13
• Status Verified: 2015-04
• Results First Submitted QC: 2015-05-05
• Last Update Submitted: 2015-05-05
• Results First Posted: 2015-05-08
• Last Update Posted: 2015-05-08

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 55

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

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Treatment (RT and CAI)	radiation therapy	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
Treatment (RT and CAI)	pharmacological 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. Other: pharmacological study, radiation therapy
Treatment (RT and CAI)	carboxyamidotriazole	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

Primary Outcome Measures

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

Trial Locations

Locations (8)

University of Alabama Birmingham; 🇺🇸 Birmingham, Alabama, United States

Moffitt Cancer Center; 🇺🇸 Tampa, Florida, United States

Emory University/Winship Cancer Institute; 🇺🇸 Atlanta, Georgia, United States

Johns Hopkins University; 🇺🇸 Baltimore, Maryland, United States

Wake Forest University; 🇺🇸 Winston-Salem, North Carolina, United States

University of Texas Health Science Center at San Antonio; 🇺🇸 San Antonio, Texas, United States

Henry Ford Hospital; 🇺🇸 Detroit, Michigan, United States

University of Pennsylavania/Abramson Cancer Center; 🇺🇸 Philadelphia, Pennsylvania, United States