Glioblastoma MedDRA version: 17.1 Level: PT Classification code 10018336 Term: Glioblastoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Name: REGORAFENIB
Pharmaceutical Form: Film-coated tablet
Product Name: LOMUSTINA
Pharmaceutical Form: Capsule
Sponsors
Istituto Oncologico Veneto – IOV-IRCCS
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: •Male or female = 18 years of age •Histologically confirmed de novo glioblastoma multiforme (grade IV) •First recurrence after adjuvant treatment (surgery followed by radiotherapy and temozolomide chemotherapy with or without bevacizumab) in patients who have not received further therapeutic interventions •Documented progression of 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 •Have adequate bone marrow function, liver function, and renal function, as measured by the following laboratory assessments conducted within 7 days prior to the initiation of study treatment: -Hemoglobin >9.0 g/dl -Absolute neutrophil count (ANC) >1500/mm3 without transfusions or granulocyte colony stimulating factor and other hematopoietic growth factors -Platelet count ?100,000/µl -WBC >3.0 x 109/L -Total bilirubin =65 years) yes F.1.3.1 Number of subjects for this age range 73
Exclusion criteria
Exclusion criteria: •Are taking strong cytochrome P (CYP) CYP3A4 inhibitors (eg, clarithromycin, indinavir, itraconazole, ketoconazole, nefazodone, nelfinavir, posaconazole, ritonavir, saquinavir, telithromycin, voriconazole) or strong CYP3A4 inducers (eg, carbamazepine, phenobarbital, phenytoin, rifampin, St. John’s Wort) •Radiotherapy within 12 weeks prior to the diagnosis of progression •Have had systemic anticancer therapy including cytotoxic therapy, signal transduction inhibitors, immunotherapy, and/or hormonal therapy within 4 weeks prior to initiation of study treatment •Positioning of carmustin wafers during first or second surgery •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 •Have had prior treatment with regorafenib or any other VEGFR-targeting kinase inhibitor •Have had a major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to initiation of study treatment •Are pregnant •Are breastfeeding •Are unable to swallow oral tablets (crushing of study treatment tablets is not allowed) •Have congestive heart failure classified as New York Heart Association Class 2 or higher •Have had unstable angina (angina symptoms at rest) or new-onset angina ? 3 months prior to screening. •Have had a myocardial infarction 140 mmHg or diastolic blood pressure [DBP] > 90 mmHg) despite optimal medical management •Have had arterial thrombotic or embolic events such as cerebrovascular accident (including transient ischemic attacks), or pulmonary embolism within 6 months prior to the initiation of study treatment •Have an ongoing infection with severity of Grade 2 or above (NCI-CTCAE v 4.0) •Have a known history of human immunodeficiency virus infection •Have either active or chronic hepatitis B or C requiring treatment with antiviral therapy •Have a history of organ allograft •Have evidence or history of any bleeding diathesis (including mild hemophilia), irrespective of severity •Have had a hemorrhage or a bleeding event ? Grade 3 (NCI-CTCAE v 4.0) within 4 weeks prior to the initiation of study treatment •Have a non-healing wound, ulcer, or bone fracture •Have renal failure requiring hemodialysis or peritoneal dialysis •Have dehydration ? Grade 1 (NCI-CTCAE v 4.0) •Have interstitial lung disease with ongoing signs and symptoms at the time informed consent is obtained •Have persistent proteinuria > 3.5 g/24 hours measured by urine protein creatinine ratio from a random urine sample (? Grade 3, NCI-CTCAE v 4.0) •Have any other serious or unstable illness, or medical, psychological, or social condition, that could jeopardize the safety of the subject and/or his/her compliance with study procedures, or may interfere with the subject’s participation in the study or evaluation of the study results •Have a known hypersensitivity to any of the study drugs, study drug classes, or excipients in the formulation of the study drugs •Have any malabsorbition condition
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the role of Regorafenib in prolonging the overall survival of glioblastoma multiforme patients who progressed after surgery and Stupp regimen with or without bevacizumab;Secondary Objective: To evaluate the progression free survival (PFS), safety, objective response rate (ORR), disease control rate (DCR) in the ITT population, and the evaluation of quality of life (QoL);Primary end point(s): Overall survival, assessed from the date of randomization to the date of death from any cause;Timepoint(s) of evaluation of this end point: 3 years (LP off study: December 2017) | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): •Progression free survival, assessed from the date of randomization to the date of disease progression or to the date of death, whichever occurs first •Objective response rate, as percentage of patients achieving a complete response plus partial response •Disease control rate, as percentage of patients achieving a complete response plus partial response plus stable disease •Toxicity during the treatment, graded according to the NCI-Common Terminology Criteria for Adverse Events (CTCAE) v.4 •Quality of Life assessed by EORTC QLQ-C30 and QLQ-BN20;Timepoint(s) of evaluation of this end point: 2 years, (LP off treatment: Dicember 2016) | — |
Countries
Italy
Contacts
Public ContactGian Luca De Salvo
Servizio Sperimentazioni Cliniche e Biostatistica – IOV-IRCCS
Outcome results
None listed