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

Completed

• Conditions: Glioblastoma Multiforme
• Interventions: Drug: Regorafenib 40 MG Oral Tablet [STIVARGA]

• Registration Number: NCT04810182
• Lead Sponsor: Istituto Oncologico Veneto IRCCS

Brief Summary

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

The primary aim of the study

Study Timeline

• Study Start: 2020-09-10
• Study First Submitted: 2021-03-15
• Study First Submitted QC: 2021-03-19
• Study First Posted: 2021-03-22
• Primary Completion: 2023-12-31
• Study Completion: 2023-12-31
• Status Verified: 2024-02
• Last Update Submitted: 2024-02-07
• Last Update Posted: 2024-02-08

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 192

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)

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Glioblastoma Patients treated with Regorafenib	Regorafenib 40 MG Oral Tablet [STIVARGA]	Patients with a confirmed diagnosis of Glioblastoma for whom a decision to treat with regorafenib has been made (by the treating physician).

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Progression free survival (PFS)	From the date of enrolment to the date of disease progression or to the date of death, assessed up to 18 months	from the date of enrolment to the date of disease progression determined using RANO criteria or to the date of death, whichever occurs first.
Toxicity (Graded according to the NCI-Common Terminology Criteria for Adverse Events-CTCAE v5.0)	From the start of Regorafenib treatment up to 30 days after the end of treatment	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
Disease control rate (DCR)	Approximately 24 months	As percentage of patients achieving a complete response plus partial response plus stable disease.
Objective response rate (ORR)	Approximately 24 months	As percentage of patients achieving a complete response plus partial response

Trial Locations

Locations (29)

Policlinico Universitario di Bari; 🇮🇹 Bari, BA, Italy

IRCCS "Saverio de Bellis"; 🇮🇹 Castellana Grotte, BA, Italy

Ospedlae S. Martino; 🇮🇹 Belluno, BL, Italy

Azienda Ospedaliera Universitaria Careggi; 🇮🇹 Firenze, FI, Italy

AOU Policlinico "G.Martino"; 🇮🇹 Messina, ME, Italy

Fondazione Istiuto Giglio Cefalù; 🇮🇹 Cefalù, PA, Italy

Ospedale Generale Regionale " F.Miulli "; 🇮🇹 Acquaviva Delle Fonti, BA, Italy

Ospedale Bellaria; 🇮🇹 Bologna, BO, Italy

Ospedale Perrino; 🇮🇹 Brindisi, BR, Italy

Università e ASST Spedali Civili; 🇮🇹 Brescia, BS, Italy

Ospedale Generale Provinciale; 🇮🇹 Macerata, MC, Italy

Irst-Irccs; 🇮🇹 Meldola, FC, Italy

Ospedale Santa Maria Annunziata; 🇮🇹 Bagno A Ripoli, FI, Italy

Ospedale Civile di Livorno; 🇮🇹 Livorno, LO, Italy

Ospedale Humanitas; 🇮🇹 Rozzano, MI, Italy

Aulss6 Euganea Padova Sud Ospedali Riuniti; 🇮🇹 Piove Di Sacco, PD, Italy

Istituto Neurologico C. Besta IRCCS; 🇮🇹 Milano, MI, Italy

Ospedale del Mare; 🇮🇹 Napoli, NL, Italy

Azienda Ospedaliero Universitaria di Pisa; 🇮🇹 Pisa, PI, Italy

Istituto Nazionale Tumori Regina Elena -IFO; 🇮🇹 Roma, RM, Italy

Policlinico Universitario Gemelli; 🇮🇹 Roma, RM, Italy

Ospedale di Rovigo; 🇮🇹 Rovigo, RO, Italy

Azienda Ospedaliero Universitaria di Siena; 🇮🇹 Siena, SI, Italy

Ospedale San Donà di Piave _Azienda ULSS 4 " Veneto Orientale"; 🇮🇹 San Dona di Piave, VE, Italy

Azienda Ospedaliero Universitaria della Città della Salute e della Scienza; 🇮🇹 Torino, TO, Italy

AULSS 7 Distretto 2 Ospedale Santorso; 🇮🇹 Santorso, VI, Italy

Azienda Ospedaliera Santa Maria; 🇮🇹 Terni, TR, Italy

Azienda Sanitaria Universitaria Friuli Centrale; 🇮🇹 Udine, Italy

AULSS 9 Scaligera Ospedale Mater Salutis; 🇮🇹 Legnago, VR, Italy