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Glioblastoma MultiformePhase 2REGOMANCT02926222

Regorafenib in Relapsed Glioblastoma

A Phase 2 study testing Regorafenib and Lomustine in people with Glioblastoma Multiforme, run by Istituto Oncologico Veneto IRCCS at 10 sites in Italy.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This study aims to evaluate the role of Regorafenib in prolonging the overall survival of glioblastoma multiforme patients who progressed after surgery and Stupp regimen with or without bevacizumab. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Glioblastoma Multiforme
What is being tested?
Regorafenib and Lomustine
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
119 participants
Where
10 sitesItaly
Study dates
Nov 2015to Jun 2021
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
  • 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:
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  • 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.
  • 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

Who cannot join

  • 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
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  • 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

Trial locations and contacts

10 sites in 1 country.

10 sites in 1 country

Italy10 sites

  • Azienda Ospedaliera "G.Rummo"

    Benevento, BR

  • Ospedale di Bellaria

    Bologna, BO

  • IRCCS "Saverio de Bellis

    Castellana Grotte, BA, 70013

  • istituto Scientifico Romagnolo per lo Studio e Cura dei Tumori

    Cesena, FC, 47014

  • Istituto Neurologico C. Besta IRCCS

    Milan, MI, 20133

  • Istituto Oncologico Veneto IRCCS, Oncologia Medica 1

    Padova, PD, 35128

  • Ospedale Santa Chiara

    Pisa, PI, 56126

  • Istituto Nazionale Tumori Regina Elena

    Roma, 00144

  • Azienda Ospedaliera Universitaria Città della Salute e della Scienza

    Torino, 10126

  • Azienda Ospedaliero Universitaria S. Maria della Misericordia

    Udine, UD, 33100

Other trials in Italy

About this study

Official title: Regorafenib in Relapsed Glioblastoma REGOMA Study Randomized, Controlled Open-label Phase II Clinical Trial

This study aims to evaluate the role of Regorafenib in prolonging the overall survival of glioblastoma multiforme patients who progressed after surgery and Stupp regimen with or without bevacizumab.

Read the detailed description

The primary aim of the study is to evaluate the overall survival (OS) in the intention to treat (ITT) population. Secondary aims are to evaluate the progression free survival (PFS), safety, objective response rate (ORR), disease control rate (DCR) in the ITT population, and the evaluation of quality of life (QoL). Additional exploratory objectives include the analysis of antiangiogenic and metabolic biomarkers in tissue at first and second surgery (if performed) by the evaluation of certain metabolic features of tumors that could be involved in tumor responses to antiangiogenic drugs.

Being tested
Regorafenib, Lomustine
Medical subject headings
Glioblastoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • RegorafenibDrug

    Also called Stivarga

    Regorafenib is formulated as tablets of 40mg for oral administration.

  • LomustineDrug

    Also called Ceenu

    Lomustine is formulated as tablets of 40mg for oral administration.

Study groups in NCT02926222
Study groupRoleWhat they receive
ARM A - RegorafenibExperimentalPatients receive REGORAFENIB 40 mg tablets once daily (160 mg/die), 3 weeks on, 1 week off, until disease progression or unacceptable toxicity.
Receives: Drug: Regorafenib
ARM B - LomustineActive comparatorPatients receive LOMUSTINE 110 mg/m2 orally on day 1, every 6 weeks (q6w), until disease progression or unacceptable toxicity.
Receives: Drug: Lomustine

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Overall survival

    Measured: From the date of randomization to 18 months or to the date of death from any cause

Secondary outcomes (4)

  1. Progression free survival

    Measured: From the date of randomization to 18 months or to the date of disease progression or to the date of death, whichever occurs first

  2. Objective response rate

    As percentage of patients achieving a complete response plus partial response

    Measured: Approximately 36 months

  3. Disease control rate

    As percentage of patients achieving a complete response plus partial response plus stable disease

    Measured: Approximately 36 months

  4. Toxicity (Graded according to the NCI-Common Terminology Criteria for Adverse Events)

    Graded according to the NCI-Common Terminology Criteria for Adverse Events (CTCAE) v.4

    Measured: Approximately every 4 weeks through the treatment period up to 30 days after the end of treatment

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted6 Oct 2016 (estimated)
  2. Study startNov 2015
  3. Primary completionJul 2017
  4. Study completionJun 2021

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
119 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02926222
Sponsor's protocol ID
IOV-GB-1-2014 REGOMA
Other IDs
2014-003722-41, 2014
Acronym
REGOMA
Status last verified
Sep 2022
First submitted
22 Jun 2016
Last updated
9 Sep 2022
Results posted
No
Data monitoring committee
No
Individual data sharing
Undecided

Publications

  • Lombardi G, Del Bianco P, Brandes AA, Eoli M, Ruda R, Ibrahim T, Lolli I, Rizzato S, Daniele B, Pace A, Pasqualetti F, Caccesse M, Bergo E, Magni G, De Salvo GL, Zagonel V. Patient-reported outcomes in a phase II randomised study of regorafenib compared with lomustine in patients with relapsed glioblastoma (the REGOMA trial). Eur J Cancer. 2021 Sep;155:179-190. doi: 10.1016/j.ejca.2021.06.055. Epub 2021 Aug 10.

    PubMed 34388515

  • Lombardi G, De Salvo GL, Brandes AA, Eoli M, Ruda R, Faedi M, Lolli I, Pace A, Daniele B, Pasqualetti F, Rizzato S, Bellu L, Pambuku A, Farina M, Magni G, Indraccolo S, Gardiman MP, Soffietti R, Zagonel V. Regorafenib compared with lomustine in patients with relapsed glioblastoma (REGOMA): a multicentre, open-label, randomised, controlled, phase 2 trial. Lancet Oncol. 2019 Jan;20(1):110-119. doi: 10.1016/S1470-2045(18)30675-2. Epub 2018 Dec 3.

    PubMed 30522967

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Regorafenib and Lomustine in people with Glioblastoma Multiforme, run by Istituto Oncologico Veneto IRCCS at 10 sites in Italy.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 25 inclusion and 31 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 9 Sep 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 10 sites in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Overall survival (time frame: From the date of randomization to 18 months or to the date of death from any cause). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02926222, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Sep 2022.

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