Status and phase
Conditions
Treatments
Study type
Funder types
Identifiers
About
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.
Enrollment
Sex
Ages
Volunteers
Inclusion criteria
NOTE: Patients with known isocitrate dehydrogenase (IDH) 1 and 2 are to be excluded.
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:
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:
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.
Exclusion criteria
Received any prior treatment for glioma including:
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.
Primary purpose
Allocation
Interventional model
Masking
36 participants in 2 patient groups
Loading...
Central trial contact
Gian Luca De Salvo, MD
Data sourced from clinicaltrials.gov
Clinical trials
Research sites
Resources
Legal