Ph I/II Study of NMS-03305293+TMZ in Adult Patients With Recurrent Glioblastoma

Running, not enrolling · Phase 1/Phase 2

Conditions studied: Glioblastoma, Diffuse Glioma

In brief

Multicenter, open-label, single-arm Phase 1/2 study on the safety and efficacy of the combination of NMS-03305293 and temozolomide (TMZ) in adult patients with diffuse gliomas (Phase 1) and isocitrate dehydrogenase (IDH) wild type glioblastoma (Phase 2) at first relapse.

Key facts

Study ID

NCT04910022

Run by

Nerviano Medical Sciences

People needed

150

Starts

2021-12-01

Expected to finish

2027-09-07

Last updated by the study team

2025-08-19

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Phase 1
• Histologically confirmed diagnosis of an intracranial diffuse glioma (i.e. diffuse astrocytoma, oligodendroglioma or glioblastoma). Sponsor may opt to restrict enrollment based on MGMT status, tumor type, tumor measurability or apply restriction on time to first relapse.
• Patients at first radiographic relapse after chemotherapy including temozolomide as long as no more than 12 cycles of temozolomide were administered.
• Patients may have been operated for recurrence. If operated:
• residual and measurable disease after surgery is not required but pathology must have confirmed tumor recurrence.
• a post-surgery MRI should be available within 48 hours following surgery.
• surgery completed at least 2 weeks before enrolment and patient clinical status should not be worsened respect to pre-surgery condition
• Backfill cohorts
• Histologically confirmed diagnosis of Glioblastoma, IDH-wildtype as per WHO 2021 classification, including IDH-wildtype diffuse and astrocytic glioma in adults if there is microvascular proliferation or necrosis or TERT promoter mutation or EGFR gene amplification or +7/-10 chromosome copy number changes or c-IMPACT-NOW 3 definition including diffuse astrocytic glioma, IDH-wildtype, with molecular features of glioblastoma, WHO Grade 4. IDH1 status must be assessed locally by immunohistochemistry (IHC). If IHC is performed and is negative, and patient is < 55 years old, sequencing or a PCR-based validated test must be performed to exclude other IDH1 or IDH2 most frequent mutations. Sponsor may opt to restrict enrollment based on MGMT status or apply restriction on time to first relapse.
• Patients must have measurable disease and meet standard of care resection, if indicated, and irradiation, if indicated, with concomitant temozolomide plus up to 6 cycles of adjuvant temozolomide consistent with local standards of care.
• Patients may have been operated for recurrence. If operated:
• residual and measurable disease after surgery is required
• a post-surgery MRI should be available within 48 hours following surgery
• surgery completed at least 2 weeks before enrolment and patient clinical status should not be worsened respect to pre-surgery condition.
• Phase 2
• Histologically confirmed diagnosis of Glioblastoma, IDH-wildtype as per WHO 2021 classification, including IDH-wildtype diffuse and astrocytic glioma in adults if there is microvascular proliferation or necrosis or TERT promoter mutation or EGFR gene amplification or +7/-10 chromosome copy number changes or c-IMPACTNOW 3 definition including diffuse astrocytic glioma, IDH-wildtype, with molecular features of glioblastoma, WHO Grade 4. IDH1 status must be assessed locally by immunohistochemistry (IHC). If IHC is performed and is negative, and patient is < 55 years old, sequencing or a PCR-based validated test must be performed to exclude other IDH1 or IDH2 most frequent mutations. Sponsor may opt to restrict enrollment based on MGMT status or apply restriction on time to first relapse.
• Patients must have measurable disease at first radiographic relapse after initial standard therapy including temozolomide as long as no more than 6 cycles of adjuvant temozolomide were administered and provided that patient completed standard of care concurrent temozolomide and the radiation therapy; multiple surgeries are allowed as long as patient is at first relapse and TMZ was administered as standard of care.
• Patients may have been operated for recurrence. If operated:
• residual and measurable disease after surgery is required
• a post-surgery MRI should be available within 48 hours following surgery
• surgery completed at least 2 weeks before enrolment and patient clinical status should not be worsened respect to pre-surgery condition.
• Phase 1 (including backfill) and Phase 2
• For non-operated patients with measurable disease in Phase I, for backfill and for all patients in Phase 2, recurrent disease must be defined by at least one bidimensionally measurable contrast-enhancing lesion with clearly defined margins with minimal diameters of 10 mm, visible on 2 or more axial slices 5 mm apart, based on MRI scan done within two weeks prior to enrolment.
• Patients on steroids should have stable or decreasing dose of steroids for 7 days prior to the baseline MRI scan.
• Life expectancy of at least 3 months.

You may not qualify if…

• Current enrollment in another interventional clinical trial.
• Current treatment with other anticancer agents or devices, or treatment at recurrence with carmustine wafer implants and proteasome inhibitors.
• Previous treatment with PCV (procarbazine, lomustine and vincristine) or any of its components, carmustine wafer implants, or bevacizumab.
• Previous treatment with PARP inhibitors.
• Major surgery, other than surgery for recurrent diffuse glioma, within 4 weeks prior to treatment.
• Standard radiotherapy within the three months (12 weeks) prior to the diagnosis of progression unless the progression is clearly outside the radiation field (eg, beyond the high-dose region or 80% isodose line) or unless the recurrence is histologically proven.
• Prior radiotherapy with a dose over 65 Gy, stereotactic radiosurgery or brachytherapy, unless the recurrence is histologically proven.
• Use of full-dose anticoagulants unless the INR or aPTT is within therapeutic limits (according to the medical standard in the institution) and the patient has been on a stable dose of anticoagulants for at least two weeks before enrollment
• Treatment with concomitant medications known to be sensitive substrates of CYP2D6 and CYP2C19 that cannot be replaced with another treatment.
• Treatment with enzyme-inducing anti-epileptic drugs (EIAED). Patients may be on non-EIAED or not be taking any anti-epileptic drugs. Patients previously on EIAED must be fully switched to non-EIAED at least 2 weeks prior to enrolment.
• Pregnant or breast-feeding women.
• Known hypersensitivity to any component of NMS-03305293 or TMZ drug formulations.
• Known active infections (bacterial, fungal, viral including HIV positivity) requiring systemic treatment.
• Patients with QTc interval ≥460 milliseconds for women, ≥450 milliseconds for men or with risk factors for torsade de pointes (e.g., uncontrolled heart failure, uncontrolled hypokalemia, history of prolonged QTc interval or family history of long QT syndrome). For patients receiving treatment with concomitant medications known to prolong the QTc interval, replacement with another treatment prior to enrollment is mandatory. If concomitant use of anti-emetics is considered essential for the care of the patients, instruction in protocol will be followed.
• Active gastrointestinal disease (e.g., documented gastrointestinal ulcer, Crohn's disease, ulcerative colitis, or short gut syndrome) or other syndromes that would impact on drug absorption.
• Any of the following in the past 6 months: myocardial infarction, unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident or transient ischemic attack, active bleeding disorder.
• Prior invasive malignancy (except for non melanoma skin cancer, carcinoma in situ or localized cancer) unless the patient has been disease-free and off therapy for that disease for ≥ 3 years.
• Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or study drug administration or may interfere with the interpretation of study results and, in the judgment of the Investigator, would make the patient inappropriate for entry into this study or could compromise protocol objectives in the opinion of the Investigator and/or the Sponsor.

Where it is running

• Mayo Clinic Hospital - Phoenix — Phoenix, Arizona, United States
• University of California Irvine Medical Center (UCIMC) - Chao Family Comprehensive Cancer Center — Orange, California, United States
• Mayo Clinic Florida — Jacksonville, Florida, United States
• Dana-Farber Cancer Institute — Boston, Massachusetts, United States
• Mayo Clinic Cancer Center — Rochester, Minnesota, United States
• Memorial Sloan-Kettering Cancer Center — New York, New York, United States
• UT Southwestern Medical Center — Dallas, Texas, United States
• The University of Texas MD Anderson Cancer Center — Houston, Texas, United States
• University of Utah, University Hospital — Salt Lake City, Utah, United States
• University of Virginia Health System — Charlottesville, Virginia, United States
• Swedish Medical Center - First Hill Campus — Seattle, Washington, United States
• IRCCS Istituto delle Scienze Neurologiche di Bologna — Bologna, Italy
• IRCCS Istituto Neurologico Carlo Besta — Milan, Italy
• Istituto Oncologico Veneto - IRCCS — Padova, Italy
• Istituto Clinico Humanitas — Rozzano, Italy
• Erasmus Medical Center — Rotterdam, Netherlands
• PanOncology Trials (Pan American Center for Oncology Trials, LLC) — Rio Piedras, Puerto Rico
• University Hospital Zurich — Zurich, Switzerland

Full record on ClinicalTrials.gov

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