Aflibercept, Radiation Therapy, and Temozolomide in Treating Patients With Newly Diagnosed or Recurrent Glioblastoma Multiforme, Gliosarcoma, or Other Malignant Glioma

NCT00650923 | Completed Phase 1

• 5 other identifiers: NCI-2009-00678CDR0000590174NABTC-07-01NABTC07-01U01CA137443
• Study Type: interventional
• Target: 61
• Locations: 1 country
• Sites: 9

Brief Summary

This phase I trial is studying the side effects and best dose of aflibercept when given together with radiation therapy and temozolomide in treating patients with newly diagnosed or recurrent glioblastoma multiforme, gliosarcoma, or other malignant glioma. Aflibercept may stop the growth of tumor cells by blocking blood flow to the tumor. Radiation therapy uses high-energy x-rays to kill tumor cells. Drugs used in chemotherapy, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving aflibercept together with radiation therapy and temozolomide may kill more tumor cells.

Conditions

Adult Anaplastic Astrocytoma; Adult Anaplastic Oligodendroglioma; Adult Giant Cell Glioblastoma; Adult Glioblastoma; Adult Gliosarcoma; Adult Mixed Glioma; Recurrent Adult Brain Tumor

Outcome Measures

Primary Outcomes (1)

• Maximum tolerated dose of aflibercept defined as the dose at which fewer than one-third of patients experience DLT based on the CTC severity grading

  28 days

Secondary Outcomes (2)

• Efficacy in terms of antitumor activity based on clinical, radiographic, and biologic assessments

  Up to 3 months

• Plasma aflibercept (VEGF Trap) concentrations and PK parameters such as Cmax, Tmax, area under the plasma concentration-time curve (AUCo-t and AUC), clearance (CL), apparent volume of distribution at steady state (Vdss), and terminal half-life (t1/2)

  Baseline and days 15, 16, 22, 29, 57, 85 of course 1 for patients in Arm I; baseline and days 2, 8, 15, 43, 71 of course 1 for patients in Arms 2 and 3

Study Arms (1)

Arm 1

EXPERIMENTAL

See Detailed Description

Drug: ziv-aflibercept; Procedure: radiation therapy; Drug: temozolomide; Procedure: pharmacological study; Procedure: laboratory biomarker analysis

Interventions

ziv-aflibercept DRUG

Given IV

Also known as: aflibercept, vascular endothelial growth factor trap, VEGF Trap, Zaltrap

Arm 1

radiation therapy PROCEDURE

Undergo RT

Also known as: irradiation, radiotherapy, therapy, radiation

Arm 1

temozolomide DRUG

Given PO

Also known as: SCH 52365, Temodal, Temodar, TMZ

Arm 1

pharmacological study PROCEDURE

Correlative studies

Also known as: pharmacological studies

Arm 1

laboratory biomarker analysis PROCEDURE

Correlative studies

Arm 1

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

Criteria: * Creatinine \< = 1.5 mg/dL or creatinine clearance = \> 60 mL/min * At least 28 days since prior major surgery or open biopsy * INR \< = 1.5 * Not pregnant or nursing * Negative pregnancy test * Karnofsky performance status 60-100% * SGOT and SGPT \< 2 times upper limit of normal (ULN) * Bilirubin \< 2 times ULN * Life expectancy = \> 12 weeks * WBC = \> 3,000/μL * ANC= \> 1,500/mm³ * Platelet count = \> 100,000/mm³ * Hemoglobin = \> 10 g/dL (transfusion allowed) * At least 21 days since prior radiotherapy (groups 2 and 3) * No prior Gliadel® wafers * No concurrent major surgery * Fertile patients must use effective contraception prior to, during, and for at least 6 months after completion of study treatment * At least 28 days since prior significant traumatic injury No evidence of bleeding diathesis or coagulopathy * No serious or nonhealing wound, ulcer, or bone fracture * No history of other cancer (except nonmelanoma skin cancer or carcinoma in situ of the cervix), unless in complete remission and off of all therapy for that disease for a minimum of 3 years * No history of abdominal fistula, gastrointestinal perforation, intra-abdominal abscess gastrointestinal bleeding or diverticulitis within the past 6 months * No prior cranial radiotherapy (group 1 only) * No prior aflibercept * No prior treatment for brain tumors, except concurrent radiotherapy and temozolomide or 2 or fewer 28-day courses of adjuvant temozolomide (groups 2 and 3) * No prior or concurrent cytotoxic drug therapy, non-cytotoxic drug therapy, or experimental drug therapy for brain tumors (group 1 only) * No concurrent major surgery * No known hypersensitivity to CHO cell products or other recombinant human antibodies * No history of hypersensitivity to a recombinant protein whereby reaction occurs during or immediately after infusion * No history of allergic reactions attributed to compounds of similar chemical or biological composition to other study agents * No uncontrolled intercurrent illness including, but not limited to, ongoing or active infection or psychiatric illness or social situation that would limit compliance with study requirements * No clinically significant cardiovascular disease within the past 6 months, including any of the following: History of ischemic or hemorrhagic stroke * Myocardial infarction, coronary artery bypass graft, or unstable angina * New York Heart Association class III-IV congestive heart failure, serious cardiac arrhythmia requiring medication, or unstable angina pectoris * Clinically significant peripheral vascular disease * Pulmonary embolism, deep vein thrombosis, or other thromboembolic event * No disease that will obscure toxicity or dangerously alter drug metabolism * Recovered from all prior therapy * More than 28 days since prior and no concurrent investigational agents * More than 7 days since prior core biopsy * At least 23 days since prior temozolomide (groups 2 and 3) * No concurrent combination antiretroviral therapy for HIV-positive patients * No concurrent full-dose anticoagulants (e.g., warfarin or low molecular-weight heparin) * Prophylactic doses allowed * No concurrent routine prophylactic use of filgrastim (G-CSF) * No other concurrent anticancer therapy (including chemotherapy, radiotherapy, hormonal treatment, or immunotherapy) * Concurrent enzyme-inducing antiepileptic drugs (EIAED) or non-EIAED allowed * Urine protein:creatinine ratio \< = 1 or 24-hour urine protein \< = 500 mg * No significant medical illnesses that in the investigator's opinion cannot be adequately controlled with appropriate therapy or would compromise the patient's ability to tolerate therapy

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (9)

University of California at Los Angeles (UCLA )

Los Angeles, California, 90095, United States

Location

UCSF-Mount Zion

San Francisco, California, 94115, United States

Location

University of California San Francisco Medical Center-Parnassus

San Francisco, California, 94143, United States

Location

Adult Brain Tumor Consortium

Baltimore, Maryland, 21231-1000, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

Massachusetts General Hospital

Charlestown, Massachusetts, 02129, United States

Location

Memorial Sloan-Kettering Cancer Center

New York, New York, 10065, United States

Location

University of Pittsburgh

Pittsburgh, Pennsylvania, 15232, United States

Location

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Astrocytoma; Oligodendroglioma; Glioblastoma; Gliosarcoma; Glioma; Brain Neoplasms

Interventions

aflibercept; Radiotherapy; Radiation; Temozolomide

Condition Hierarchy (Ancestors)

Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Therapeutics; Physical Phenomena; Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Patrick Wen

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 1, 2008
• First Posted: April 2, 2008
• Study Start: July 1, 2008
• Primary Completion: June 1, 2013
• Study Completion: December 1, 2013
• Last Updated: May 30, 2014

Record last verified: 2014-04

Locations

US (9)