Two arms trial with bevacizumab and fotemustine in patients with brain tumor previously treated.

Phase 1

• Conditions: Glioblastoma multiforme progressed after a first line treatment with temozolomide and radiotherapy.; MedDRA version: 14.1Level: PTClassification code 10018337Term: Glioblastoma multiformeSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2011-001363-46-IT
• Lead Sponsor: ROCHE

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2011-12-29
• Last Update Posted: 13 June 2016

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: Not specified

Inclusion Criteria

Disease-specific inclusion criteria: 1. Histologically confirmed recurrent glioblastoma multiforme (grade IV) 2. First recurrence after standard adjuvant treatment (surgery followed by radiotherapy and temozolomide chemotherapy) in patients who have not received further therapeutic interventions 3. Patients must have measurable disease defined by RANO criteria as bidimensionally contrast enhancing lesions with clearly defined margins by MRI scans with two perpendicular diameters of at least 10 mm visible on two or more axial slices 4. Progression of documented disease as defined by RANO criteria at least 12 weeks after completion of radiotherapy, unless the recurrence is outside the radiation field or has been histologically documented 5. Patients may have undergone surgery for the recurrence; the histological report must document a glioblastoma recurrence. If operated: - residual and measurable disease after surgery is not required but surgery must have confirmed the recurrence - a post-surgery MRI should be available within 48 hours following surgery at least 28 days interval from the surgery is required prior to administration of study drugs and patients should have fully recovered 6. Target lesions should be measurable in two dimensions 7. WHO Performance status = 2 (or KPS =50) 8. Stable or decreasing dosage of steroids for 7 days prior to the baseline MRI scan General inclusion criteria: 1. Age = 18 years 2. Female patients of childbearing potential must have a negative serum pregnancy test within 7 days prior to enrolment into the study or within 14 days (with a confirmatory urine pregnancy test within 7 days prior to the first study treatment). Patients (men and women) must agree to use medically accepted contraceptive methods throughout the study and for the 6 months following the last administration of bevacizumab or for 60 days following the last administration of fotemustine 3. With the exception of alopecia, resolution of all acute toxic effects of any prior surgery, radiotherapy, radiosurgery or chemotherapy to NCI CTC (Version 4.0) grade = 1 and to the baseline laboratory values 4. Signed informed consent Hematological, biochemical and organ function: 1. Adequate bone marrow function: absolute neutrophil count (ANC) = 2.0 x 109/L platelet count = 100 x 109/L Hb = 9 g/dL (may be transfused to maintain or exceed this level) 2. Adequate liver function: total bilirubin = 1.5 x ULN AST, ALT = 2.5 x ULN albumin > 25 g/L 3. Adequate renal function: serum creatinine = 1.25 x ULN Urine dipstick for proteinuria < 2+. Patients discovered to have = 2+ proteinuria on dipstick urinalysis at baseline should undergo a 24-hour urine collection and must demonstrate = 1.0 g of protein in 24 hours OR Urine protein/creatinine ratio (UPC) = 1.0 4. International normalized ratio (INR) or PT (secs) and activated partial thromboplastin time (aPTT): – in the absence of therapeutic intent to anticoagulate the subject: INR=1.5 or PT =1.5 x ULN and aPTT =1.5 x ULN – in the presence of therapeutic intent to anticoagulate the subject: INR or PT and aPTT within therapeutic limits (according to the medical standard in the institution) NOTE: Use of full-dose anticoagulants is permitted as long as the INR or aPTT is within therapeutic limits (according to the medical standard in the institution) and the patient has been on a stable dose of anticoagulants for at least two weeks before randomization.
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Exclusion Criteria

Cancer-related exclusion criteria: 1. No prior treatment with bevacizumab or other VEGF inhibitors or VEGF receptors signaling inhibitors 2. Residual relevant toxicity (grade >1 according to NCI CTC version 4.0) resulting from previous therapy 3. Radiotherapy within the 3 months prior to the diagnosis of progression 4. Chemotherapy in the previous 4 weeks 5. Other active or inactive malignancy (except for carcinoma in situ of the cervix, of the prostate or basal cell carcinoma). Malignancy will be considered inactive if patients are in complete remission for at least 3 years prior to study entry 6. Evidence of recent hemorrhage on MRI of the brain. However, patients with clinically asymptomatic presence of hemosiderin, resolving hemorrhagic changes related to surgery, and presence of punctate hemorrhage in the tumor are permitted entry into the study General exclusion criteria 1.Clinically significant cardiovascular diseases, such as congestive heart failure (NYHA class II, III and IV), unstable angina pectoris or myocardial infarction within 6 months prior to study entry 2.Uncontrolled hypertension (systolic blood pressure >150 mmHg and/or diastolic blood pressure >100 mmHg on treatment) or history of hypertensive crises or hypertensive encephalopathy 3.History of stroke or transient ischemic attack (TIA) within 6 months prior to study entry 4.Clinically significant vascular disease or symptomatic peripheral vascular disease 5.Presence or history of recurrent thromboembolism (>1 episode of deep venous thrombosis or peripheral embolism) during the past 2 years, inherited bleeding diathesis or coagulation disorder 6.Chronic treatment with acetylsalicylic acid >325 mg daily or clopidogrel >75 mg daily 7.History of abdominal or tracheo-esophageal fistula, gastrointestinal perforation or intra-abdominal abscess within 6 months prior to study entry 8.History of pulmonary embolism or cerebral hemorrhage 9.Unhealed surgical wound, skin ulcer or bone fracture 10.History of active gastrointestinal ulcer 11.Immunodeficiency disorders, including patients with positive HIV test 12.Active infections 13.Any other clinical condition or laboratory abnormality that could, according to the investigator, make the patient inappropriate for this study 14.Patients who cannot be reassessed by MRI 15.Invasive procedures (major surgery, open biopsy or significant traumatic injury) within 28 days prior to study entry, or major elective surgery already planned during the treatment phase of the study. The central venous catheter (CVC) positioning procedure should be planned within at least 2 days before the administration of the drug. 16.Pregnancy or breast-feeding 17.Subjects with reproductive potential not willing to undergo pregnancy test or to use effective method of contraception. Female patients must be postmenopausal (12 months of amenorrhea), surgically sterile or they must agree to use a physical method of contraception for at least 6 months . Oral or injectable contraceptive agents cannot be the sole method of contraception. Male patients must be surgically sterile or agree to use a barrier method of contraception for at least 6 months. 18.Any investigational drug within 4 weeks prior to study start 19.Known hypersensitivity to any component or excipient of the study drugs 20.Patients assessed by the investigator to be unable or unwilling to comply with the requirements of the protocol.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified