Regorafenib in Relapsed Glioblastoma (REGOMA)
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. Read our disclaimer for details. |
ClinicalTrials.gov Identifier: NCT02926222 |
Recruitment Status :
Completed
First Posted : October 6, 2016
Last Update Posted : September 9, 2022
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Condition or disease | Intervention/treatment | Phase |
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Glioblastoma Multiforme | Drug: Regorafenib Drug: Lomustine | Phase 2 |
Study Type : | Interventional (Clinical Trial) |
Actual Enrollment : | 119 participants |
Allocation: | Randomized |
Intervention Model: | Parallel Assignment |
Masking: | None (Open Label) |
Primary Purpose: | Treatment |
Official Title: | Regorafenib in Relapsed Glioblastoma REGOMA Study Randomized, Controlled Open-label Phase II Clinical Trial |
Actual Study Start Date : | November 2015 |
Actual Primary Completion Date : | July 2017 |
Actual Study Completion Date : | June 2021 |
Arm | Intervention/treatment |
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Experimental: ARM A - Regorafenib
Patients receive REGORAFENIB 40 mg tablets once daily (160 mg/die), 3 weeks on, 1 week off, until disease progression or unacceptable toxicity.
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Drug: Regorafenib
Regorafenib is formulated as tablets of 40mg for oral administration.
Other Name: Stivarga |
Active Comparator: ARM B - Lomustine
Patients receive LOMUSTINE 110 mg/m2 orally on day 1, every 6 weeks (q6w), until disease progression or unacceptable toxicity.
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Drug: Lomustine
Lomustine is formulated as tablets of 40mg for oral administration.
Other Name: Ceenu |
- Overall survival [ Time Frame: From the date of randomization to 18 months or to the date of death from any cause ]
- Progression free survival [ Time Frame: From the date of randomization to 18 months or to the date of disease progression or to the date of death, whichever occurs first ]
- Objective response rate [ Time Frame: Approximately 36 months ]As percentage of patients achieving a complete response plus partial response
- Disease control rate [ Time Frame: Approximately 36 months ]As percentage of patients achieving a complete response plus partial response plus stable disease
- Toxicity (Graded according to the NCI-Common Terminology Criteria for Adverse Events) [ Time Frame: Approximately every 4 weeks through the treatment period up to 30 days after the end of treatment ]Graded according to the NCI-Common Terminology Criteria for Adverse Events (CTCAE) v.4
- Quality of life EORTC [ Time Frame: From the date of randomization, approximately every 3 months until the date of first documented progression or date of death from any cause, or study withdrawal, whichever came first, assessed up to 30 months. ]
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Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
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
- For patients not undergoing a second surgery at the time of relapse, recurrent disease must include at least one bi-dimensionally measurable contrast-enhancing lesion with clearly defined margins by MRI scan, with minimal diameters of 10 mm, visible on 2 or more axial slices 5 mm apart, based on an MRI scan done within 2 weeks prior to randomization
- 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
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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 (<5 x upper limit of normal for patients with liver involvement of their cancer and/or have bone metastasis)
- Serum creatinine <1.5 x upper limit of normal
- Alkaline phosphatase <2.5 x ULN (<5 x upper limit of normal for patients with liver involvement of their cancer and/or have bone metastasis)
- PT-INR/PTT <1.5 x upper limit of normal (Patients who are being therapeutically anticoagulated with an agent such as coumadin or heparin will be allowed to participate provided that no prior evidence of underlying abnormality in these parameters exists per medical history)
- Lipase ≤ 1.5 x the ULN
- Glomerular filtration rate ≥ 30 mL/min/1.73 m2 according to the Modified Diet in Renal Disease abbreviated formula
- Analyses of MGMT methylation status on tumoral tissue at first surgery (at own institution)
- Understand, be willing to give consent, and sign the written informed consent form (ICF) prior to undergoing any study-specific procedure
- If female and of childbearing potential, have a negative result on a pregnancy test performed a maximum of 7 days before initiation of study treatment
- If female and of childbearing potential, or if male, agree to use adequate contraception (eg, intrauterine device, oral contraceptive, or double-barrier method) based on the judgment of the investigator or a designated associate from the date on which the ICF is signed until 8 weeks after the last dose of study drug
- World Health Organization (WHO) Performance status ≤ 1 (or Karnofsky performance status (KPS) ≥70)) within 14 days prior to the initiation of study treatment
- Stable or decreasing dosage of steroids for 7 days prior to the baseline MRI scan.
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Patients may have undergone surgery for the recurrence; the histological report must document a glioblastoma recurrence. If operated:
- at least 28 days and maximum 42 days interval from the surgery is required prior to administration of study drugs and patients should have fully recovered
- 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, if the lesion is in the radiation field,
- 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 < 6 months prior to initiation of study treatment
- Have cardiac arrhythmias requiring anti-arrhythmic therapy, with the exception of beta blockers or digoxin
- Have uncontrolled hypertension (systolic blood pressure [SBP] > 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 malabsorption condition
- Recurrent disease located outside of the brain
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02926222
Italy | |
IRCCS "Saverio de Bellis | |
Castellana Grotte, BA, Italy, 70013 | |
Ospedale di Bellaria | |
Bologna, BO, Italy | |
Azienda Ospedaliera "G.Rummo" | |
Benevento, BR, Italy | |
istituto Scientifico Romagnolo per lo Studio e Cura dei Tumori | |
Cesena, FC, Italy, 47014 | |
Istituto Neurologico C. Besta IRCCS | |
Milano, MI, Italy, 20133 | |
Istituto Oncologico Veneto IRCCS, Oncologia Medica 1 | |
Padova, PD, Italy, 35128 | |
Ospedale Santa Chiara | |
Pisa, PI, Italy, 56126 | |
Azienda Ospedaliero Universitaria S. Maria della Misericordia | |
Udine, UD, Italy, 33100 | |
Istituto Nazionale Tumori Regina Elena | |
Roma, Italy, 00144 | |
Azienda Ospedaliera Universitaria Città della Salute e della Scienza | |
Torino, Italy, 10126 |
Principal Investigator: | Vittorina Zagonel, MD | Istituto Oncologico Veneto IRCCS |
Responsible Party: | Istituto Oncologico Veneto IRCCS |
ClinicalTrials.gov Identifier: | NCT02926222 |
Other Study ID Numbers: |
IOV-GB-1-2014 REGOMA 2014-003722-41 ( EudraCT Number ) |
First Posted: | October 6, 2016 Key Record Dates |
Last Update Posted: | September 9, 2022 |
Last Verified: | September 2022 |
Individual Participant Data (IPD) Sharing Statement: | |
Plan to Share IPD: | Undecided |
Glioblastoma Astrocytoma Glioma Neoplasms, Neuroepithelial Neuroectodermal Tumors Neoplasms, Germ Cell and Embryonal Neoplasms by Histologic Type Neoplasms |
Neoplasms, Glandular and Epithelial Neoplasms, Nerve Tissue Lomustine Antineoplastic Agents, Alkylating Alkylating Agents Molecular Mechanisms of Pharmacological Action Antineoplastic Agents |