Ph I/II Study of NMS-03305293+TMZ in Adult Patients With Recurrent Glioblastoma (NCT04910022) | Clinical Trial Compass
Active — Not RecruitingPhase 1/2
Ph I/II Study of NMS-03305293+TMZ in Adult Patients With Recurrent Glioblastoma
United States150 participantsStarted 2021-12-01
Plain-language summary
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.
Who can participate
Age range18 Years
SexALL
See this in plain English?
AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.
Inclusion criteria
✓. 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:
✓. 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:
✓. 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.
What they're measuring
1
Phase 1: Number of Participants with first-cycle dose limiting toxicity
Timeframe: Time interval between the first dose administration in Cycle 1 and the first dose administration in Cycle 2 which is expected to be 28 days or up to 42 days in case of dose delay due to drug related toxicity
2
Phase 2: Objective Response Rate
Timeframe: From the date of first response up to data cut-off (approximately 18 months)
✓. 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.
Exclusion criteria
✕. 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