A Phase Ib/II Study of AZD2171 in Combination With Daily Temozolomide and Radiation in Patients With Newly Diagnosed Glioblastoma Not Taking Enzyme-Inducing Anti-epileptic Drugs

NCI-2009-00267

This phase I/II trial is studying the side effects and best dose of cediranib to see how well it works when given together with temozolomide and radiation therapy in treating patients with newly diagnosed glioblastoma. Cediranib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. 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. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving cediranib together with temozolomide and radiation therapy may kill more tumor cells.

2008-04-01

2014-04-01

2014-04-01

Completed

Early phase I

46

Inclusion Criteria: * Histologically confirmed glioblastoma * Newly diagnosed disease * Scheduled to receive standard post-surgical (i.e., biopsy or resection) temozolomide and radiotherapy * Must have residual, contrast-enhancing tumor (≥ 1 centimeter in ≥ 1 dimension) * Patients must be maintained on a stable corticosteroid regimen for 5 days prior to their baseline scan and for 5 days prior to their first vascular MRI; the dose of steroids should remain the same during the baseline vascular MRIs * Archival tumor tissue available for molecular analysis * No intratumoral hemorrhage or peritumoral hemorrhage by MRI * Karnofsky performance status 60-100% * Leukocytes ≥ 3,000/mcl * Absolute neutrophil count ≥ 1,500/mcL * Platelet count ≥ 100,000/mcL * Hemoglobin ≥ 8 g/dL * Total bilirubin normal * AST/ALT ≤ 2.5 times upper limit of normal * Creatinine normal OR creatinine clearance ≥ 60 mL/min * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception * Proteinuria ≤ 1+ on two consecutive dipsticks ≥ 7 days apart * Mini-mental status examination score ≥ 15 * Must be able to tolerate MRI and must consent to participate in additional Vascular Imaging Procedures per protocol * CT scans cannot be substituted for MRI * Mean QTc ≤ 500 msec (with Bazett's correction) by electrocardiogram * No concurrent malignancy except curatively treated basal cell or squamous cell carcinoma skin cancer or carcinoma in situ of the cervix or breast * Patients with prior malignancies must be disease-free for ≥ 5 years * No history of familial long QT syndrome or other significant ECG abnormality * No history of allergic reactions attributed to compounds of similar chemical or biologic composition to cediranib * No uncontrolled intercurrent illness including, but not limited to, any of the following: * Hypertension (e.g., blood pressure \> 140/90 mm Hg) * Ongoing or active infection * Symptomatic congestive heart failure * Unstable angina pectoris * Cardiac arrhythmia * Psychiatric illness/social situations that would preclude study compliance * No known coagulopathy that increases risk of bleeding * No history of clinically significant hemorrhages in the past * No New York Heart Association class III-IV heart disease * No condition requiring concurrent drugs or biologics with proarrhythmic potential * No other concurrent chemotherapy agents, investigational agents, or biologic therapy * No prior chemotherapy, radiotherapy, or any experimental therapy for this disease * No prior IV bevacizumab for any other medical condition * No prior carmustine implant (Gliadel Wafer) * No prior brachytherapy or radiosurgery for this disease * More than 30 days since prior and no other concurrent investigational agents or participation in an investigational therapeutic trial * At least 2 weeks since prior and no concurrent enzyme-inducing anti-epileptic drugs (EIAEDs) * Concurrent non-EIAEDs allowed * No concurrent CYP450-inducing anticonvulsants * No concurrent anticoagulants (e.g., dalteparin, warfarin, or low-molecular weight heparin) * If patients require warfarin or other anticoagulants (e.g., low-molecular weight heparin) while on study, then patient may continue treatment * No concurrent combination antiretroviral therapy for HIV-positive patients * No concurrent VEGF inhibitors * No concurrent pentamidine * No concurrent herbal or nontraditional medications

{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE1', 'PHASE2'], 'designInfo': {'allocation': 'NA', 'interventionModel': 'SINGLE_GROUP', 'primaryPurpose': 'TREATMENT', 'maskingInfo': {'masking': 'NONE'}}, 'enrollmentInfo': {'count': 46, 'type': 'ACTUAL'}}

2023-06-06