Regorafenib in Bevacizumab Refractory Recurrent Glioblastoma

NCT04051606 | Completed Phase 2 DMC

• 1 other identifier: CASE7318
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to determine the safety and tolerability of Regorafenib in patients with recurrent or progressive glioblastoma (GBM) who have progressed on bevacizumab. Regorafenib is FDA approved administered as monotherapy during the study. 22 total patients are expected to participate in this study. Even though a participant may meet all the criteria for participation, it is possible that they will not be enrolled in this study.

Conditions

Recurrent Glioblastoma

Outcome Measures

Primary Outcomes (1)

• Median overall survival (OS)

  Median overall survival (OS) in patients with recurrent or progressive GBM who have progressed on bevacizumab.

  Up to 3 years from start of treatment

Secondary Outcomes (4)

• Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]

  Up to 3 years from start of treatment

• Objective response rate (ORR)

  Up to 3 years from start of treatment

• Progression free survival at 6 months (PFS-6).

  at 6 months from start of treatment

• Median time to progression (TTP)

  Up to 3 years from start of treatment

Study Arms (1)

Regorafenib

EXPERIMENTAL

160 mg regorafenib 3 weeks on/ one week off in participants with Avastin refractory Glioblastoma, continued until progression or toxicity. Participants will receive an MRI every 8 weeks.

Drug: Regorafenib

Interventions

Regorafenib DRUG

Regorafenib is a monotherapy during the study, oral administration at 160 mg once daily will be administered for 3 weeks on /1 week off.

Regorafenib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• The participant (or legally representative if applicable) provides written informed consent for the trial.
• Patients with histologically confirmed glioblastoma or other grade IV malignant glioma (i.e. gliosarcoma, small cell glioblastoma, etc.), recurrent after prior external-beam fractionated radiotherapy and temozolomide chemotherapy.
• Patients with documented radiographic progression following bevacizumab therapy for treatment of glioblastoma
• Patients with up to 3 prior recurrences are allowed (patients could have received bevacizumab or bevacizumab containing regimen either in first or second recurrence).
• Karnofsky performance status ≥ 70%.
• Patients must have the following laboratory values:
• Absolute neutrophil count (ANC) ≥ 1.5 x 109/L
• Platelets ≥ 100 x 109/L
• Hemoglobin (Hgb) \> 9 g/dL
• Serum total bilirubin: ≤ 1.5 x ULN
• ALT and AST ≤ 3.0 x ULN
• Serum creatinine ≤ 1.5 x ULN
• Blood coagulation parameters: INR ≤ 1.5
• Minimum interval since completion of radiation treatment is 12 weeks
• Minimum interval since last drug therapy:

You may not qualify if:

• Patients who have had previous treatment with Regorafenib
• Patients who have undergone major surgery (e.g. intra-thoracic, intra-abdominal or intra-pelvic), open biopsy or significant traumatic injury ≤ 4 weeks prior to starting study drug, or patients who have had minor procedures, percutaneous biopsies or placement of vascular access device ≤ 1 week prior to starting study drug, or who have not recovered from side effects of such procedure or injury
• Patients with impaired cardiac function or clinically significant cardiac diseases, including any of the following:
• Congestive heart failure - New York Heart Association (NYHA) \> Class II
• History or presence of serious uncontrolled ventricular arrhythmias. Cardiac arrhythmias requiring anti-arrhythmic therapy other than beta blockers or digoxin.
• Clinically significant resting bradycardia (defined as bradycardia that required intervention)
• Active coronary artery disease defined as Any of the following within 6 months prior to starting study drug: myocardial infarction (MI), severe/unstable angina, Coronary Artery Bypass Graft (CABG)
• Cerebrovascular Accident (CVA), Transient Ischemic Attack (TIA), Pulmonary Embolism (PE) in the last 6 months
• Uncontrolled hypertension (defined by a SBP ≥ 160 mm Hg or DBP ≥ 100 mm Hg despite anti-hypertensive medications)
• Patients with cirrhosis, or active viral or nonviral hepatitis.
• Known diagnosis of human immunodeficiency virus (HIV) infection (HIV testing is not mandatory)
• Other concurrent severe and/or uncontrolled concomitant medical conditions (e.g. active or uncontrolled infection, uncontrolled diabetes) that could cause unacceptable safety risks or compromise compliance with the protocol
• Pregnant or breast-feeding women
• Patients with known hypersensitivity to Chinese hamster ovary cell products or other recombinant human, chimeric, or humanized antibodies
• Patients with active bleeding or pathologic conditions that carry a high risk of bleeding, (i.e. hereditary hemorrhagic telangiectasia).

Sponsors & Collaborators

• Case Comprehensive Cancer Center: lead

Study Sites (1)

Cleveland Clinic Taussig Cancer institute, Case Comprehensive Cancer Center

Cleveland, Ohio, 44195, United States

Location

MeSH Terms

Conditions

Glioblastoma

Interventions

regorafenib

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Study Officials

• David Peereboom, MD

  Cleveland Clinic Taussig Cancer institute, Case Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 7, 2019
• First Posted: August 9, 2019
• Study Start: July 31, 2019
• Primary Completion: March 20, 2024
• Study Completion: March 20, 2024
• Last Updated: June 5, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: CSR

Locations

US (1)