Ph I/II Study of NMS-03305293+TMZ in Adult Patients With Recurrent Glioblastoma
- Conditions
- GlioblastomaDiffuse Glioma
- Registration Number
- NCT04910022
- Lead Sponsor
- Nerviano Medical Sciences
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- All
- Target Recruitment
- 150
Inclusion Criteria:<br><br> - Phase 1<br><br> 1. Histologically confirmed diagnosis of an intracranial diffuse glioma (i.e.<br> diffuse astrocytoma, oligodendroglioma or glioblastoma). Sponsor may opt to<br> restrict enrollment based on MGMT status, tumor type, tumor measurability or<br> apply restriction on time to first relapse.<br><br> 2. Patients at first radiographic relapse after chemotherapy including<br> temozolomide as long as no more than 12 cycles of temozolomide were<br> administered.<br><br> 3. Patients may have been operated for recurrence. If operated:<br><br> - residual and measurable disease after surgery is not required but<br> pathology must have confirmed tumor recurrence.<br><br> - a post-surgery MRI should be available within 48 hours following surgery.<br><br> - surgery completed at least 2 weeks before enrolment and patient clinical<br> status should not be worsened respect to pre-surgery condition<br><br> - Backfill cohorts<br><br> 1. Histologically confirmed diagnosis of Glioblastoma, IDH-wildtype as per WHO<br> 2021 classification, including IDH-wildtype diffuse and astrocytic glioma in<br> adults if there is microvascular proliferation or necrosis or TERT promoter<br> mutation or EGFR gene amplification or +7/-10 chromosome copy number changes or<br> c-IMPACT-NOW 3 definition including diffuse astrocytic glioma, IDH-wildtype,<br> with molecular features of glioblastoma, WHO Grade 4. IDH1 status must be<br> assessed locally by immunohistochemistry (IHC). If IHC is performed and is<br> negative, and patient is < 55 years old, sequencing or a PCR-based validated<br> test must be performed to exclude other IDH1 or IDH2 most frequent mutations.<br> Sponsor may opt to restrict enrollment based on MGMT status or apply<br> restriction on time to first relapse.<br><br> 2. Patients must have measurable disease and meet standard of care resection, if<br> indicated, and irradiation, if indicated, with concomitant temozolomide plus up<br> to 6 cycles of adjuvant temozolomide consistent with local standards of care.<br><br> 3. Patients may have been operated for recurrence. If operated:<br><br> - residual and measurable disease after surgery is required<br><br> - a post-surgery MRI should be available within 48 hours following surgery<br><br> - surgery completed at least 2 weeks before enrolment and patient clinical<br> status should not be worsened respect to pre-surgery condition.<br><br> - Phase 2<br><br> 1. Histologically confirmed diagnosis of Glioblastoma, IDH-wildtype as per WHO<br> 2021 classification, including IDH-wildtype diffuse and astrocytic glioma in<br> adults if there is microvascular proliferation or necrosis or TERT promoter<br> mutation or EGFR gene amplification or +7/-10 chromosome copy number changes or<br> c-IMPACTNOW 3 definition including diffuse astrocytic glioma, IDH-wildtype,<br> with molecular features of glioblastoma, WHO Grade 4. IDH1 status must be<br> assessed locally by immunohistochemistry (IHC). If IHC is performed and is<br> negative, and patient is < 55 years old, sequencing or a PCR-based validated<br> test must be performed to exclude other IDH1 or IDH2 most frequent mutations.<br> Sponsor may opt to restrict enrollment based on MGMT status or apply<br> restriction on time to first relapse.<br><br> 2. Patients must have measurable disease at first radiographic relapse after<br> initial standard therapy including temozolomide as long as no more than 6<br> cycles of adjuvant temozolomide were administered and provided that patient<br> completed standard of care concurrent temozolomide and the radiation therapy;<br> multiple surgeries are allowed as long as patient is at first relapse and TMZ<br> was administered as standard of care.<br><br> 3. Patients may have been operated for recurrence. If operated:<br><br> - residual and measurable disease after surgery is required<br><br> - a post-surgery MRI should be available within 48 hours following surgery<br><br> - surgery completed at least 2 weeks before enrolment and patient clinical<br> status should not be worsened respect to pre-surgery condition.<br><br> - Phase 1 (including backfill) and Phase 2<br><br> 4. For non-operated patients with measurable disease in Phase I, for backfill and<br> for all patients in Phase 2, recurrent disease must be defined by at least one<br> bidimensionally measurable contrast-enhancing lesion with clearly defined<br> margins with minimal diameters of 10 mm, visible on 2 or more axial slices 5 mm<br> apart, based on MRI scan done within two weeks prior to enrolment.<br><br> 5. Patients on steroids should have stable or decreasing dose of steroids for 7<br> days prior to the baseline MRI scan.<br><br> 6. Life expectancy of at least 3 months.<br><br> 7. Able to undergo brain MRI scans with IV gadolinium.<br><br> 8. No evidence of symptomatic and acute intratumoral hemorrhage on MRI. Patients<br> with MRI demonstrating old hemorrhage or subacute blood after a neurosurgical<br> procedure (biopsy or resection) are eligible.<br><br> 9. Sufficient tissue representative of the disease available for central MGMT<br> promoter methylation status (Phase I and II) and IDH status evaluation (Phase<br> I).<br><br> 10. Male or female patients with age = 18 years.<br><br> 11. ECOG performance status =2.<br><br> 12. Signed and dated IEC or IRB-approved Informed Consent.<br><br> 13. Resolution of all acute toxic effects (excluding alopecia) of any prior<br> anticancer therapy to NCI CTCAE (Version 5.0) Grade = 1 or to the baseline<br> laboratory values as defined in Inclusion Criterion Number 14.<br><br> 14. Baseline laboratory values fulfilling the requirements declared into the<br> Protocol<br><br> 15. Patients must use highly effective contraception or true abstinence. Female<br> patients of childbearing potential must agree to use effective contraception or<br> abstinence during the period of therapy and in the following 6 months plus 5x<br> NMS-03305293 half-life (3 days) after discontinuation of study treatment. Being<br> NMS-03305293 a potential CYP3A perpetrator, hormonal contraception may lose<br> efficacy while on treatment with NMS-03305293, therefore this should be taken<br> into account. Male patients must be surgically sterile or must agree to use<br> highly effective contraception or true abstinence during the period of therapy<br> and in the following 90 days plus 5x NMS-03305293 half-life (3 days) after<br> discontinuation of study treatment.<br><br> 16. Ability to swallow capsules intact (without chewing, crushing, or opening).<br><br> 17. Willingness and ability to comply with scheduled visits, treatment plan,<br> laboratory tests and other study indications or procedures.<br><br>Exclusion Criteria:<br><br> 1. Current enrollment in another interventional clinical trial.<br><br> 2. Current treatment with other anticancer agents or devices, or treatment at<br> recurrence with carmustine wafer implants and proteasome inhibitors.<br><br> 3. Previous treatment with PCV (procarbazine, lomustine and vincri
Not provided
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Phase 1: Number of Participants with first-cycle dose limiting toxicity;Phase 2: Objective Response Rate
- Secondary Outcome Measures
Name Time Method