Regorafenib in Patients With Relapsed Glioblastoma. IOV-GB-1-2020 REGOMA-OSS

Study Overview
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Brief Summary
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This study aims to analyze the role the of Regorafenib in prolonging the Overall Survival of glioblastoma multiforme patients who progressed after surgery and a first-line chemo-radiotherapy treatment in the setting of real world life.

Detailed Description
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The primary aim of the study

Official Title
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Regorafenib in Relapsed Glioblastoma. An Observational, Multicentric and Prospective Study. IOV-GB-1-2020 REGOMA-OSS

Conditions
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Glioblastoma Multiforme

Intervention / Treatment
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* Drug: Regorafenib 40 MG Oral Tablet [STIVARGA]


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female ≥ 18 years of age Histologically confirmed glioblastoma (grade IV) First recurrence after adjuvant treatment (surgery followed by radiotherapy and temozolomide chemotherapy) in patients who have not received further therapeutic interventions World Health Organization (WHO) Performance status ≤ 1 (or Karnofsky performance status (KPS) ≥70)) before the start of the treatment 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. Documented progression of disease by a brain MRI scan done within 14 days before the start of treatment with Regorafenib. Stable or decreasing dosage of steroids for 7 days prior to the baseline MRI scan. 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 White blood cell count (WBC) >3.0 x 109/L Total bilirubin <1.5 times the upper limit of normal ALT and AST <3 x upper limit of normal Serum creatinine <1.5 x upper limit of normal Alkaline phosphatase <2.5 x ULN (<5 x upper limit of normal value) PT-INR/PTT <1.5 x upper limit of normal Lipase ≤ 1.5 x the ULN Glomerular filtration rate ≥ 30 mL/min/1.73 m2 TSH, fT3,fT4 within normal limits Patients may have undergone surgery for the recurrence; the histological report must document a glioblastoma recurrence. If operated: at least 28 days from the surgery is required prior to Regorafenib administration and patients should have fully recovered. Exclusion Criteria: Have had prior treatment with regorafenib or any other VEGFR-targeting kinase inhibitor Have had systemic anticancer therapy including cytotoxic therapy, signal transduction inhibitors, immunotherapy, and/or hormonal therapy within 4 weeks prior to initiation of treatment Recurrent disease located outside of the brain Have uncontrolled hypertension (systolic blood pressure [SBP] > 140 mmHg or diastolic blood pressure [DBP] > 90 mmHg) despite optimal medical management Have had a myocardial infarction < 6 months prior to initiation of treatment with Regorafenib 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 treatment with Regorafenib Have either active or chronic hepatitis B or C requiring treatment with antiviral therapy 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)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Glioblastoma Patients treated with Regorafenib<br>Patients with a confirmed diagnosis of Glioblastoma for whom a decision to treat with regorafenib has been made (by the treating physician). | Drug: Regorafenib 40 MG Oral Tablet [STIVARGA]<br>* As per the treating physicians discretion<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival (OS) | Overall Survival is defined as the time from date of enrolment to the date of death due to any cause | From the enrolment date to the date of death, for any cause, or to the last follow-up, assessed up to 18 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression free survival (PFS) | from the date of enrolment to the date of disease progression determined using RANO criteria or to the date of death, whichever occurs first. | From the date of enrolment to the date of disease progression or to the date of death, assessed up to 18 months | 
| Objective response rate (ORR) | As percentage of patients achieving a complete response plus partial response | Approximately 24 months | 
| Disease control rate (DCR) | As percentage of patients achieving a complete response plus partial response plus stable disease. | Approximately 24 months | 
| Toxicity (Graded according to the NCI-Common Terminology Criteria for Adverse Events-CTCAE v5.0) | Toxicity during the treatment will be recorded and graded according to the NCICommon Terminology Criteria for Adverse Events (CTCAE) v.4.. , related to severity of the adverse event from Grade 1 to Grade 5 | From the start of Regorafenib treatment up to 30 days after the end of treatment |