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Regorafenib in Bevacizumab Refractory Recurrent Glioblastoma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04051606
Recruitment Status : Recruiting
First Posted : August 9, 2019
Last Update Posted : August 28, 2019
Sponsor:
Information provided by (Responsible Party):
Case Comprehensive Cancer Center

Tracking Information
First Submitted Date  ICMJE August 7, 2019
First Posted Date  ICMJE August 9, 2019
Last Update Posted Date August 28, 2019
Actual Study Start Date  ICMJE July 31, 2019
Estimated Primary Completion Date December 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 7, 2019)
Median overall survival (OS) [ Time Frame: Up to 3 years from start of treatment ]
Median overall survival (OS) in patients with recurrent or progressive GBM who have progressed on bevacizumab.
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT04051606 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: August 9, 2019)
  • Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] [ Time Frame: Up to 3 years from start of treatment ]
    Safety and tolerability of regorafenib by CTCAE version 5.0. Safety and tolerability will be defined by the percent of participants experiencing >= grade 3 AE/SAE
  • Objective response rate (ORR) [ Time Frame: Up to 3 years from start of treatment ]
    ORR by modified RANO criteria. ORR defined by modified RANO criteria . The percentage of patients that have at least 50% reduction in their tumor size in 2 dimensions.
  • Progression free survival at 6 months (PFS-6). [ Time Frame: at 6 months from start of treatment ]
    Survival and absence of progressive disease at 6 months, with progression defined as >25% in the sum of products of the perpendicular diameters of CE lesions; evidence of new lesion(s).
  • Median time to progression (TTP) [ Time Frame: Up to 3 years from start of treatment ]
    Time that takes a median patient to progress defined as >25% in the sum of products of the perpendicular diameters of CE lesions; evidence of new lesion(s).
Original Secondary Outcome Measures  ICMJE
 (submitted: August 7, 2019)
  • Safety and tolerability of regorafenib [ Time Frame: Up to 3 years from start of treatment ]
    Safety and tolerability of regorafenib by CTCAE version 5.0. Safety and tolerability will be defined by the percent of participants experiencing >= grade 3 AE/SAE
  • Objective response rate (ORR) [ Time Frame: Up to 3 years from start of treatment ]
    ORR by modified RANO criteria. ORR defined by modified RANO criteria . The percentage of patients that have at least 50% reduction in their tumor size in 2 dimensions.
  • Progression free survival at 6 months (PFS-6). [ Time Frame: at 6 months from start of treatment ]
    Survival and absence of progressive disease at 6 months, with progression defined as >25% in the sum of products of the perpendicular diameters of CE lesions; evidence of new lesion(s).
  • Median time to progression (TTP) [ Time Frame: Up to 3 years from start of treatment ]
    Time that takes a median patient to progress defined as >25% in the sum of products of the perpendicular diameters of CE lesions; evidence of new lesion(s).
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Regorafenib in Bevacizumab Refractory Recurrent Glioblastoma
Official Title  ICMJE Regorafenib in Bevacizumab Refractory Recurrent Glioblastoma
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.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Recurrent Glioblastoma
Intervention  ICMJE Drug: Regorafenib
Regorafenib is a monotherapy during the study, oral administration at 160 mg once daily will be administered for 3 weeks on /1 week off.
Study Arms  ICMJE Experimental: Regorafenib
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.
Intervention: Drug: Regorafenib
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: August 7, 2019)
22
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 2021
Estimated Primary Completion Date December 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • 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:
  • 3 weeks since last non-cytotoxic therapy
  • 3 weeks must have elapsed since the completion of a non-nitrosourea containing chemotherapy regimen
  • 6 weeks since the completion of a nitrosourea containing chemotherapy regimen.
  • Women of childbearing potential must have a negative serum pregnancy test performed within 7 days prior to the start of study drug. Post-menopausal women (defined as no menses for at least 1 year) and surgically sterilized women are not required to undergo a pregnancy test. The definition of adequate contraception will be based on the judgment of the investigator.
  • Subjects (men and women) of childbearing potential must agree to use adequate contraception beginning at the signing of the ICF until at least2 months after the last dose of study drug. The definition of adequate contraception will be based on the judgment of the principal investigator or a designated associate.
  • Patients must have no concurrent malignancy except curatively treated basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix and breast, adequately treated stage I or II cancer from which the patient is in complete remission. Patients with other prior malignancies must be disease-free for ≥ three years.
  • Patients must be maintained on a stable or decreasing corticosteroid regimen from the time of their baseline scan until the start of treatment and/or for at least 5 days before starting treatment. The maximum dosing of corticosteroid therapy is 4mg/day.
  • Life expectancy of at least 12 weeks (3 months).
  • Subject must be able to swallow and retain oral medication.

Exclusion Criteria:

  • 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).
  • Patients who are currently receiving anticoagulation treatment (warfarin is not allowed, low weight heparin is allowed). Evidence or history of bleeding diathesis or coagulopathy.
  • Patients unwilling or unable to comply with the protocol
  • Any hemorrhage or bleeding event ≥ NCI CTCAE v5.0 Grade 3 within 4 weeks prior to start of study medication.
  • Patients with phaeochromocytoma.
  • Ongoing infection > Grade 2 NCI-CTCAE v5.0.
  • Presence of a non-healing wound, non-healing ulcer, or bone fracture.
  • Persistent proteinuria ≥ Grade 3 NCI-CTCAE v5.0 (> 3.5 g/24 hrs, measured by urine protein: creatinine ratio on a random urine sample).
  • Interstitial lung disease with ongoing signs and symptoms at the time of informed consent.
  • Pleural effusion or ascites that causes respiratory compromise (≥ NCI-CTCAE version 5.0 Grade 2 dyspnea).
  • Known or suspected allergy or hypersensitivity to any of the study drugs, study drug classes, or excipients of the formulations given during the course of this trial.
  • Any malabsorption condition.
  • Women who are pregnant or breast-feeding.
  • Any condition which, in the investigator's opinion, makes the subject unsuitable for trial participation.
  • Substance abuse, medical, psychological or social conditions that may interfere with the subject's participation in the study or evaluation of the study results.

Excluded therapies and medications, previous and concomitant

  • Concurrent anti-cancer therapy (chemotherapy, radiation therapy, surgery, immunotherapy, biologic therapy, or tumor embolization) other than study treatment (regorafenib, other agents being investigated in combination with regorafenib).
  • Prior use of regorafenib.
  • Concurrent use of another investigational drug or device therapy (i.e., outside of study treatment) during, or within 4 weeks of trial entry (signing of the informed consent form).
  • Major surgical procedure, open biopsy, or significant traumatic injury within 28 days before start of study medication.
  • Therapeutic anticoagulation with Vitamin-K antagonists (e.g., warfarin)
  • Use of any herbal remedy (e.g. St. John's wort [Hypericum perforatum]).
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Manmeet Ahluwalia, MD +1 216-444-6145 ahluwam@ccf.org
Contact: Pamela Lackner +1 216-444-0437 lacknep@ccf.org
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04051606
Other Study ID Numbers  ICMJE CASE7318
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Case Comprehensive Cancer Center
Study Sponsor  ICMJE Case Comprehensive Cancer Center
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Case Comprehensive Cancer Center
Verification Date August 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP