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Glioblastoma, IDH-wildtypePhase 1REGOMA-2NCT06095375

Regorafenib With Temozolomide With or Without RT in MGMT-Methylated, IDH Wild-type GBM Patients

A Phase 1 study testing Regorafenib and Temozolomide in people with Glioblastoma, IDH-wildtype and MGMT-Methylated Glioblastoma, run by Istituto Oncologico Veneto IRCCS at 2 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 will evaluate the addition of regorafenib to standard of care treatment with TMZ as adjuvant therapy, and in combination with TMZ+RT as concomitant therapy. The standard of care for newly diagnosed GBM (ndGBM) includes surgical resection to the extent that is safely feasible, followed by RT plus concomitant… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Regorafenib and Temozolomide
Could I receive a placebo?
No, everyone receives an active treatment
How many people
21 participants
Where
2 sitesItaly
Study dates
4 Jul 2022to 22 Dec 2025
Phase
Phase 1
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

  • Males and females of ≥ 18 years of age at the time of signing the informed consent form (ICF).
  • Subject must understand and voluntarily sign an ICF prior to any study-related assessments/procedures being conducted
  • Patients capable of taking oral medication
  • Subject is willing and able to adhere to the study visit schedule and other protocol requirements.
  • Histologically confirmed Grade IV GBM/gliosarcoma (WHO criteria; non-IDH R132Hmutant by immunohistochemistry [IHC] or, sequencing for IDH1 and 2 in case of patients >55 years) established following either a radical or partial surgical resection. This includes treatment naïve (chemotherapy and RT) patients with prior histologically diagnosis of lower-grade astrocytoma that has been upgraded to a histologically verified glioblastoma after a subsequent definitive surgery.
  • NOTE: Patients with known isocitrate dehydrogenase (IDH) 1 and 2 are to be excluded.
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  • Methylated MGMT according to local laboratory (in case of pyrosequencing, methylation >10%)
  • Subject must have recovered from the effects of surgery, including post-operative infections or complications. Toxicities resulting from surgery must have resolved to NCI CTCAE (v5.0) Grade ≤ 1 prior to starting regorafenib treatment (with the exception of Grade 2 alopecia).
  • For Concomitant Therapy Cohort: Prior tumor resection up to 7 weeks prior to the first dose of regorafenib.
  • For Adjuvant Therapy Cohort: Subject must have recently completed standard course of radiotherapy with TMZ chemotherapy, and then have an MRI documenting stable disease prior to the first dose of regorafenib (In case of "pseudoprogression" the patient will not be eligible)
  • For Adjuvant Therapy:
  • All AEs resulting from prior RT+TMZ chemotherapy must have resolved to NCI CTCAE (v5.0) Grade 1 (except for laboratory parameters outlined below).
  • Subject must have not experienced significant toxicity to prior RT+TMZ (i.e., Grade 4 hematological toxicity)
  • Subjects must have life expectancy of at least 6 months
  • Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 to 1 (or KPS 70)
  • Corticosteroid use of dexamethasone 4 mg or less per day within 7 days before starting regorafenib.
  • Subject must have the following laboratory values at screening within 7 days before starting regorafenib:
  • Absolute neutrophil count (ANC) ≥ 1.5 x 109/L without growth factor support for 7 days (14 days if subject received pegfilgrastim).
  • Hemoglobin (Hgb) ≥10 g/dL
  • Platelet count (plt) ≥100x 109/L
  • Serum potassium concentration within normal range, or correctable with supplements
  • Serum glutamic oxaloacetic transaminase (SGOT)/aspartate aminotransferase (AST) and serum glutamate pyruvic transaminase (SGPT)/alanine aminotransferase (ALT) ≤ 3.0 x Upper Limit of Normal (ULN).
  • Serum total bilirubin ≤ 1.5 x ULN
  • Serum creatinine ≤ 1.5 x ULN or measured glomerular filtration rate (GFR) ≥ 50 mL/min/1.73 m2 using an exogenous filtration marker such as iohexol, inulin, 51Cr EDTA or 1125 iothalamate, or creatinine clearance of ≥ 50 mL/min using Cockroft-Gault equation.
  • Serum albumin > 3.5 g/dL
  • PT (or INR) and APTT within normal range
  • For women who are not postmenopausal (i.e., < 2 years after last menstruation) or surgically sterile (absence of ovaries and/or uterus) and who are sexually active: agreement to use an adequate method of contraception (oral contraceptives, intrauterine contraceptive device, or barrier method of contraception in conjunction with spermicidal jelly) during the Treatment period and for at least 6 months after the last dose of study drug.
  • For male patients who are partners of premenopausal women: agreement to use a barrier method of contraception during the Treatment period and for at least 6 months after the last dose of study drug.
  • Participants with type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are eligible to participate.

Who cannot join

  • Received any prior treatment for glioma including:
  • Prior prolifeprospan 20 with carmustine wafer.
  • Prior intracerebral agent.
  • Prior radiation treatment for GBM or lower-grade glioma.
  • Prior chemotherapy or immunotherapy for GBM or lower-grade glioma.
  • NOTE: 5-aminolevulinic acid-mediated photodynamic therapy and Flourcrescein administered prior to surgery to aid in optimal surgical resection is not considered a chemotherapy agent.
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  • Patients who performed biopsy as surgical approach of glioblastoma.
  • Patients who 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).
  • Patients who are receiving additional, concurrent, active therapy for GBM outside of the trial.
  • Disease located outside of the brain (e.g. brainstem and leptomeningeal disease).
  • Candidate for urgent palliative intervention for primary disease (e.g., impending herniation) as judged by the Investigator
  • History of allergy or hypersensitivity to any of the study treatments or any of their excipients.
  • In the presence of therapeutic intent to anticoagulate the patient: INR or PT and aPTT not within therapeutic limits (according to the medical standard in the institution). NOTE: Per American Society of Clinical Oncology (ASCO) guidelines, use of low-molecular-weight heparin (LMWH) should be the preferred approach.
  • Unable or unwilling to undergo brain MRI scans with intravenous (IV) gadolinium.
  • History of another malignancy in the previous 3 years, with a disease-free interval of< 3 years. Patients with prior history of in situ cancer or basal or squamous cell skin cancer are eligible.
  • Serious, non-healing wound, ulcer, bone fracture, or abscess.
  • Any cerebrovascular accident (including transient ischemic attacks) within the last 6 months prior to initiation of study treatment.
  • Have an ongoing infection with severity of Grade 2 or above (CTCAE 5.0)
  • Any hemorrhage or bleeding event that is ≥ Grade 3 based on the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Event (CTCAE), Grade 2 intracranial hemorrhage, or persistent thrombotic/embolic event within 4 weeks prior to the start of study medication.
  • Uncontrolled or severe cardiac disease (e.g., history of unstable angina, myocardial infarction, coronary stenting, or bypass surgery within the last 6 months prior to initiation of study treatment), symptomatic congestive heart failure, serious uncontrolled cardiac arrhythmia (including atrial flutter/fibrillation), requirement for inotropic support or use of devices for cardiac conditions (e.g., pacemakers/defibrillators), or hypertension (participants with systolic blood pressure[BP] of > 160 mmHg or diastolic BP of > 100 mmHg despite optimal medical management are to be excluded).
  • History of interstitial lung disease, history of slowly progressive dyspnea and unproductive cough, sarcoidosis, silicosis, idiopathic pulmonary fibrosis, pulmonary hypersensitivity pneumonitis, or symptomatic pleural effusion.
  • Active, known, or suspected auto-immune disease, including systemic lupus erythematosus, Hashimotos thyroiditis, scleroderma, polyarteritis nodosa, or auto-immune hepatitis.
  • Known history of hepatitis B, human immunodeficiency virus (HIV), or active hepatitis C infection requiring treatment with antiviral therapy. Note: HIV testing is not required in the absence of clinical suspicion.
  • History of bleeding diathesis (irrespective of severity).
  • Uncontrolled intercurrent illness including (e.g., symptomatic ascites), but not limited to ongoing or active infection.
  • Persistent ≥ Grade 3 Lipase (> 2.0 - 5.0 x upper limit of normal [ULN] with signs or symptoms; > 5.0 x ULN and asymptomatic).
  • Persistent proteinuria> 3.5 g/24 hours measured by urine protein creatinine ratio from a random urine sample (≥ Grade 3, CTCAE 5.0)
  • Have any malabsorbition condition.
  • Any condition that could make the subject noncompliant with the study procedures and/or study requirements, as judged by the Investigator (for example: cognitive impairment, psychiatric illness, etc).

Trial locations and contacts

2 sites in 1 country.

Italy2 sites

  • Istituto Oncologico Veneto IRCCS

    Padova, 35128

  • Humanitas Research Hospital

    Rozzano, 20089

Other trials in Italy

About this study

Official title: Regorafenib in Combination With Temozolomide With or Without Radiotherapy in Patients With Newly Diagnosed MGMT-Methylated, IDH Wild-type Glioblastoma. A Phase I Dose-finding Study

This study will evaluate the addition of regorafenib to standard of care treatment with TMZ as adjuvant therapy, and in combination with TMZ+RT as concomitant therapy.

The standard of care for newly diagnosed GBM (ndGBM) includes surgical resection to the extent that is safely feasible, followed by RT plus concomitant TMZ chemotherapy, and up to 6 months of adjuvant TMZ.

The dose escalation will be explored following a "3+3" design, escalating oral doses of regorafenib in combination with adjuvant (maintenance) TMZ (cohort A) to estimate the MTD of regorafenib as adjuvant (maintenance) therapy. After finding the MTD in the Adjuvant Therapy dose escalation, the Concomitant Therapy (cohort B) dose escalation will start, exploring escalating oral doses of regorafenib in combination with concomitant TMZ+RT, to estimate the MTD of regorafenib as concomitant therapy.

Medical subject headings
Glioblastoma

What participants receive

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

  • RegorafenibDrug

    Cohort A (Adjuvant/Maintenance Phase). The Adjuvant (Maintenance) Therapy dose escalation will explore three dose levels of regorafenib (e.g., 80 mg, 120 mg and 160 mg; level-1: regorafenib 40 mg will be evaluated in case of DLT during regorafenib 80 mg) administered in combination with adjuvant TMZ to evaluate the initial toxicity of regorafenib and TMZ Cohort B (Concomitant Phase) Therapy dose escalation will explore three dose levels of regorafenib (e.g., 80 mg, 120 mg and 160 mg; level -1: regorafenib 40 mg will be evaluated in case of DLT during regorafenib 80 mg) administered in combination with TMZ and RT.

  • TemozolomideDrug

    Following a "3+3" design, in cohort A three patients will be administered temozolomide 150-200 mg/m2 for 5 consecutive days every 28 days until 6-12 cycles and regorafenib daily for 21 days, with a 1-week washout period at dose of 80 mg (level 1), 120 mg (level 2), or 160 mg (level 3) (regorafenib 40 mg- level -1). As a general rule, one cycle will last 28 days (day 1-28); however, in the event of treatment prolongation, the cycle period will be extended.

    In cohort B,During concomitant therapy phase: temozolomide 75 mg/m2/die for 42 (max 49 days) consecutive days (concomitant with radiation therapy).

Study groups in NCT06095375
Study groupRoleWhat they receive
Cohort A (Adjuvant/Maintenance Phase)ExperimentalNot described
Receives: Drug: Regorafenib; Drug: Temozolomide
Cohort B (Concomitant Phase)ExperimentalNot described
Receives: Drug: Regorafenib; Drug: Temozolomide

What is being measured

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

  1. Number of patients with a Dose Limiting Toxicity (DLT)

    Measured: During dose escalation, the DLT evaluation period will be two cycles from Day -1 of Cycle 1 of adjuvant phase (cohort A) or from Day 1 to last day of the concomitant RT phase (Cohort B). (each cycle is 28 days)

  2. Number of patients with ≥1 adverse event (AE) using the NCI CTCAE v5.0

    • Grade 3 diarrhea, nausea, vomiting, and loss of appetite if lasting for ≥ 7 consecutive days;
    • Grade 3 electrolyte imbalance if lasting for ≥ 7 consecutive days;
    • Grade 3 dermal toxicity if lasting for ≥ 7 consecutive days;
    • Grade 3 fatigue for ≥ 7 consecutive days;
    • Grade 4 T-Bil, AST (GOT) and/or ALT (GPT) elevations,

    Measured: evaluation period will be two cycles from Day -1 of Cycle 1 of adjuvant phase (cohort A) or from Day 1 to last day of the concomitant RT phase (Cohort B). (each cycle is 28 days)

  3. Number of patients discontinuing study treatment due to an AE

    Number of patients discontinuing study treatment due to an AE

    Measured: evaluation period will be two cycles from Day -1 of Cycle 1 of adjuvant phase (cohort A) or from Day 1 to last day of the concomitant RT phase (Cohort B). (each cycle is 28 days)

Secondary outcomes (8)

  1. Pharmacokinetics parameters - AUC

    area under the plasma concentration versus time curve

    Measured: evaluation period will be two cycles from Day -1 of Cycle 1 of adjuvant phase (cohort A) or from Day 1 to last day of the concomitant RT phase (Cohort B). (each cycle is 28 days)

  2. Best response to treatment according to RANO criteria

    Tumor response according to RANO criteria

    Measured: from date of randomization until the date of first occurrence of disease progression or death, whichever come first,assessed up to 32 months

  3. Progression-free survival

    Survival time without tumor progression

    Measured: from the start of radiotherapy until the date of first occurrence of disease progression or death whichever come first,assessed up to 32 months

  4. EORTC QLQ-C30

    Survey with evaluations at screening, concurrently to brain MRI assessment and at the end of treatment

    Measured: from the start of radiotherapy until the date of first occurrence of disease progression or death whichever come first,assessed up to 32 months

  5. Pharmacokinetics parameters - Tmax

    Time to peak drug concentration

    Measured: evaluation period will be two cycles from Day -1 of Cycle 1 of adjuvant phase (cohort A) or from Day 1 to last day of the concomitant RT phase (Cohort B). (each cycle is 28 days)

  6. Pharmacokinetics parameters - Cmax

    Peak plasma concentration

    Measured: evaluation period will be two cycles from Day -1 of Cycle 1 of adjuvant phase (cohort A) or from Day 1 to last day of the concomitant RT phase (Cohort B). (each cycle is 28 days)

  7. Overall survival

    Measured: from the start of radiotherapy until death ,assessed up to 32 months

  8. Brain module BN20

    Survey with evaluations at screening, concurrently to brain MRI assessment and at the end of treatment

    Measured: from the start of radiotherapy until the date of first occurrence of disease progression or death whichever come first,assessed up to 32 months

Timeline

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

  1. First posted23 Oct 2023
  2. Study start4 Jul 2022
  3. Primary completion9 Oct 2024
  4. Study completion22 Dec 2025

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 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
21 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06095375
Sponsor's protocol ID
IOV-GB-1-2021-REGOMA2
Other IDs
2021-001604-15
Acronym
REGOMA-2
Status last verified
Jan 2026
First submitted
10 Mar 2023
Last updated
4 Nov 2026
Results posted
No
FDA-regulated drug
No
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Regorafenib and Temozolomide in people with Glioblastoma, IDH-wildtype and MGMT-Methylated Glioblastoma, run by Istituto Oncologico Veneto IRCCS at 2 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 29 inclusion and 29 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 4 Nov 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

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?

Number of patients with a Dose Limiting Toxicity (DLT) (time frame: During dose escalation, the DLT evaluation period will be two cycles from Day -1 of Cycle 1 of adjuvant phase (cohort A) or from Day 1 to last day of the concomitant RT phase (Cohort B). (each cycle is 28 days)). The study lists 3 primary outcomes in all. 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 NCT06095375.

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 4 Nov 2026.

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