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

• Status: Completed
• Trial end date: 2013-12-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: National Cancer Institute (NCI)
• Treatments: Aflibercept; Dacarbazine; Endothelial Growth Factors; Temozolomide

Criteria

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