A Phase I/II Combination Study of NMS-03305293 and Temozolomide in Adult Patients with Recurrent Glioblastoma

Phase 2

Recruiting

• Conditions: Diffuse Glioma; Glioblastoma; 10027655

• Registration Number: NL-OMON56287
• Lead Sponsor: erviano Medical Sciences Srl, Italy

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Last Update Posted: 9 April 2024

Recruitment & Eligibility

• Status: Recruiting
• Sex: Not specified
• Target Recruitment: 16

Inclusion Criteria

Patients must meet all of the following inclusion criteria to be eligible for
enrollment into the study:

Phase I
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.
3. 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

Phase II
1. 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.
2. 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
3. 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-surgey condition.

For Phase I and Phase II
4. For non-operated patients, with measurable disease in Phase I and for all
patients in Phase II, 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.
5. Patients on steroids should have stable or decreasing dose of steroids for 7
days prior to the baseline MRI scan.
6. Life expectancy of at least 3 months.
7. Able to undergo brain MRI scans with IV gadolinium.
8. 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.
9. Sufficient tissue representative of the disease available for central MGMT
promoter methylation status (Phase I and II) and IDH status evaluation (Phase
I).
10. Male or female patients with age >=18 years.
11. ECOG performance status <=2.
12. Signed and dated IEC or IRB-approved Informed Consent.
13. Resolution of all acute toxic effects (excluding alopecia) of any prior
anticancer therapy to NCI CTCAE (Ve

Exclusion Criteria

Patient Exclusion Criteria
The presence of any of the following will exclude a patient from study
enrollment:
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.
9. Treatment with concomitant medications known to be sensitive substrates of
CYP2D6 and CYP2C19 that cannot be replaced with another treatment.
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.
11. Pregnant or breast-feeding women.
12. Known hypersensitivity to any component of NMS-03305293 or TMZ drug
formulations.
13. Known active infections (bacterial, fungal, viral including HIV positivity)
requiring systemic treatment.
14. 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.
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. 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.
17. 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.
18. 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

Study & Design

• Study Type: Interventional
• Study Design: Not specified