EUCTR2020-003417-35-IT进行中（未招募）1 期
A Phase I/II Combination Study of NMS-03305293 and Temozolomide in Adult Patients with Recurrent Glioblastoma - Ph I/II Study of NMS-03305293+TMZ in Adult Patients with Recurrent Glioblastoma
ERVIANO MEDICAL SCIENCES SR0 个研究点目标入组 125 人开始时间: 2021年6月8日最近更新:
适应症
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 125
研究概览
简要总结
暂无简介。
研究设计
- 研究类型
- Interventional clinical trial of medicinal product
入排标准
- 性别
- All
入选标准
- •Phase I (except for glioblastoma expansion cohort)
- •1. Histologically confirmed diagnosis of an intracranial diffuse glioma (i.e. diffuse astrocytoma, oligodendroglioma or glioblastoma).
- •2. Patients at first relapse after chemotherapy including temozolomide as long as no more than 12 cycles of temozolomide were administered.
- •Phase II and Phase I glioblastoma expansion cohort
- •3. Histologically confirmed diagnosis of IDH wild type glioblastoma as per WHO 2016 classification 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.
- •4. Patients at first relapse after initial standard therapy including temozolomide as long as no more than 6 cycles of temozolomide were administered and provided that patient completed standard of care concurrent temozolomide and the radiation therapy.
- •Phase I and Phase II
- •5. 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/randomization and patient should have fully recovered.
- •6. For non-operated patients, 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/randomization.
- •7. Patients on steroids should have stable or decreasing dose of steroids for 7 days prior to the baseline MRI scan.
- •8. Life expectancy of at least 3 months.
- •9. Able to undergo brain MRI scans with IV gadolinium.
- •10. No evidence of symptomatic and acute intratumoral hemorrhage on MRI. Patients with MRI demonstrating old hemorrhage or subacute blood after a neurosurgical procedure (biopsy or resection) are eligible.
- •11. Sufficient tissue representative of the disease available for central MGMT promoter methylation status (Phase I and II) and IDH status evaluation (Phase I).
- •12. Male or female patients with age = 18 years.
- •13. ECOG performance status 14. Signed and dated IEC or IRB-approved Informed Consent.
- •15. Resolution of all acute toxic effects (excluding alopecia) of any prior anticancer therapy to NCI CTCAE (Version 5.0) Grade = 1 or to the baseline laboratory values
- •as defined in Inclusion Criterion Number 14.
- •16. Adequate baseline hematological, renal and hepatic functions. Negative pregnancy test for female with reproductive potential.
- •17. Female patients of childbearing potential must agree to use effective contraception or abstinence during
- •the period of therapy and in the following 6 months after discontinuation of study treatment. Male patients must be surgically sterile or must agree to use effective
- •contraception or abstinence during the period of therapy and in the following 6 months after discontinuation of study treatment.
- •18. Ability to swallow capsules intact (without chewing, crushing, or opening).
- •19. Willingness and ability to comply with scheduled visits, treatment plan, laboratory tests and other study indications or procedu
排除标准
- •1. Current enrollment in another interventional clinical trial.
- •2. Current treatment with other anticancer agents, or treatment at recurrence with carmustine wafer implants and proteasome inhibitors.
- •3. Previous treatment with PCV (procarbazine, lomustine and vincristine) or any of its components, carmustine wafer implants, or bevacizumab.
- •4. Previous treatment with PARP inhibitors.
- •5. Major surgery, other than surgery for recurrent diffuse glioma, within 4 weeks prior to treatment.
- •6. 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.
- •7. Prior radiotherapy with a dose over 65 Gy, stereotactic radiosurgery or brachytherapy, unless the recurrence is histologically proven.
- •8. 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 (Phase I) or randomization (Phase II).
- •9. Treatment with concomitant medications known to be sensitive substrates of CYP2D6 and CYP2C19 that cannot be replaced with another treatment (see Table 5).
- •10. 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/randomization.
- •11. Pregnant or breast-feeding women.
- •12. Known hypersensitivity to any component of NMS-03305293 or TMZ (Phase I, Phase II) or lomustine (Phase II) drug formulations.
- •13. Known active infections (bacterial, fungal, viral including HIV positivity) requiring systemic treatment.
- •14. Patients with QTc interval =480 milliseconds 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 should be considered. If replacement is not possible, a careful risk/benefit evaluation should be performed prior to
- •enrollment.
- •15. 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.
- •16. Planned vaccinations with live vaccines (Phase II).
- •17. 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.
- •18. Prior invasive malignancy (except for non melanoma skin cancer, carcinoma in situ of the cervix or localized cancer) unless the patient has been disease-free and off therapy for that disease for = 3 years.
- •19. History of coeliac disease and wheat allergy (Phase II).
- •20. 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 o
研究者
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