GlioblastomaPhase 1/2NCT04910022
Ph I/II Study of NMS-03305293+TMZ in Adult Patients With Recurrent Glioblastoma
A Phase 1/2 study testing NMS-03305293 and Temozolomide in people with Glioblastoma and Diffuse Glioma, run by Nerviano Medical Sciences at 18 sites in 5 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Glioblastoma, Diffuse Glioma
- What is being tested?
- NMS-03305293 and Temozolomide
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 150 participants
- Where
- 18 sitesin 5 countries
- Study dates
- 1 Dec 2021to 7 Sep 2027
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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
- 4. 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.
- 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 (Version 5.0) Grade ≤ 1 or to the baseline laboratory values as defined in Inclusion Criterion Number 14.
- 14. Baseline laboratory values fulfilling the requirements declared into the Protocol
- 15. Patients must use highly effective contraception or true abstinence. Female patients of childbearing potential must agree to use effective contraception or abstinence during the period of therapy and in the following 6 months plus 5x NMS-03305293 half-life (3 days) after discontinuation of study treatment. Being NMS-03305293 a potential CYP3A perpetrator, hormonal contraception may lose efficacy while on treatment with NMS-03305293, therefore this should be taken into account. Male patients must be surgically sterile or must agree to use highly effective contraception or true abstinence during the period of therapy and in the following 90 days plus 5x NMS-03305293 half-life (3 days) after discontinuation of study treatment.
- 16. Ability to swallow capsules intact (without chewing, crushing, or opening).
- 17. Willingness and ability to comply with scheduled visits, treatment plan, laboratory tests and other study indications or procedures.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
18 sites in 5 countries.
18 sites in 5 countries
United States11 sites
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215
University of Virginia Health System
Charlottesville, Virginia, 22908
UT Southwestern Medical Center
Dallas, Texas, 75390
The University of Texas MD Anderson Cancer Center
Houston, Texas, 77030
Mayo Clinic Florida
Jacksonville, Florida, 32224
Memorial Sloan-Kettering Cancer Center
New York, New York, 10065
University of California Irvine Medical Center (UCIMC) - Chao Family Comprehensive Cancer Center
Orange, California, 92868
Mayo Clinic Hospital - Phoenix
Phoenix, Arizona, 85054
Mayo Clinic Cancer Center
Rochester, Minnesota, 55905
University of Utah, University Hospital
Salt Lake City, Utah, 84112
Swedish Medical Center - First Hill Campus
Seattle, Washington, 98122
Italy4 sites
IRCCS Istituto delle Scienze Neurologiche di Bologna
Bologna, 40139
IRCCS Istituto Neurologico Carlo Besta
Milan, 20133
Istituto Oncologico Veneto - IRCCS
Padova, 35128
Istituto Clinico Humanitas
Rozzano, 20089
Puerto Rico1 site
PanOncology Trials (Pan American Center for Oncology Trials, LLC)
Rio Piedras, 00935
About this study
Official title: A Phase I/II Combination Study of NMS-03305293 and Temozolomide in Adult Patients With Recurrent Glioblastoma
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.
- Conditions
- Glioblastoma, Diffuse Glioma
- Being tested
- NMS-03305293, Temozolomide
- Keywords
- IDH wild type, PARP inhibitor
- Medical subject headings
- Glioblastoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NMS-03305293Drug
Route of administration: Oral
TemozolomideDrug
Route of administration: Oral
Commercially available temozolomide
| Study group | Role | What they receive |
|---|---|---|
| NMS-03305293 +TMZ | Experimental | Phase 1 Dose Escalation: All patients will receive NMS-03305293 and temozolomide (TMZ) administered orally (NMS-03305293 once or twice daily on days 1-7 or 28 consecutive days from Day 1 to Day 28; TMZ once daily on days 1-5;) in repeated 4-week cycles aimed at defining the Maximum Tolerated Dose (MTD) and the Recommended Phase 2 Doses (RP2Ds) of NMS-03305293 in combination with TMZ. Each cycle is 28 days.
Phase 2: Once the RP2D is defined, the patients will receive TMZ daily on days 1-5 in combination with NMS-03305293 at the RP2D on days 1-7 or on days 1-28 every 28 days.
Backfill cohorts: additional patients may be treated with TMZ daily on days 1-5 and NMS-03305293 at different dose levels/schedules that have been previously assessed and determined to be safe, in order to properly characterize the exposure relationship over a range of doses/schedules. The backfill cohorts may run in parallel. Receives: Drug: NMS-03305293; Drug: Temozolomide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Phase 1: Number of Participants with first-cycle dose limiting toxicity
Measured: 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
Phase 2: Objective Response Rate
Objective Response Rate (ORR), calculated as the proportion of evaluable patients who have achieved, as best overall response (BOR), confirmed complete response (CR) or partial response (PR) through central retrospective assessment of RANO criteria
Measured: From the date of first response up to data cut-off (approximately 18 months)
Secondary outcomes (20)
Number of participants with Adverse Events (AEs)
Safety will be assessed by adverse events (AEs), which include clinically significant abnormalities identified during a medical test (e.g. laboratory tests, electrocardiogram, vital signs, physical examinations). AEs will be coded by Medical Dictionary for Regulatory Activities (MedDRA) and their severity will be graded according to the NCI Common Terminology Criteria for Adverse Events (CTCAE, version 5.0).The analysis will focus on the events reported after the start of treatment (treatment emergent adverse events).
Measured: From the Informed Consent signature to 28 days after the last dose of study treatment administration
Maximum concentration (Cmax) of NMS-03305293 and possible identified metabolites (if appropriate) after single and multiple doses of drug
Plasma samples will be collected and used for pharmacokinetics assessments
Measured: Phase 1 and backfill cohorts: Cycle 1 (each cycle is 28 days) on Days 1, 2, 5, 6 and 8; Cycle 2 on Days 5 and 15 (day 15 only if 28 days schedule). Phase 2: Cycle 1 (Days 1 and 5), Cycle 2 (Day 5) and Cycle 3 or Cycle 4 (Day 5)
Time to observed Cmax (Tmax) of NMS-03305293 and possible identified metabolites (if appropriate) after single and multiple doses of drug
Plasma samples will be collected and used for pharmacokinetics assessments
Measured: Phase 1 and backfill cohorts: Cycle 1 (each cycle is 28 days) on Days 1, 2, 5, 6 and 8; Cycle 2 on Days 5 and 15 (day 15 only if 28 days schedule). Phase 2: Cycle 1 (Days 1 and 5), Cycle 2 (Day 5) and Cycle 3 or Cycle 4 (Day 5)
Area under the concentration-time curve up to the last detectable plasma concentration (AUClast) of NMS-03305293 and possible identified metabolites (if appropriate) after single and repeated dose of drug.
Plasma samples will be collected and used for pharmacokinetics assessments
Measured: Phase 1 and backfill cohorts: Cycle 1 (each cycle is 28 days) on Days 1, 2, 5, 6 and 8; Cycle 2 on Days 5 and 15 (day 15 only if 28 days schedule). Phase 2: Cycle 1 (Days 1 and 5), Cycle 2 (Day 5) and Cycle 3 or Cycle 4 (Day 5)
Terminal elimination half-life (t1/2) of NMS-03305293 and possible identified metabolites (if appropriate) after single and multiple doses of drug
Plasma samples will be collected and used for pharmacokinetics assessments
Measured: Phase 1 and backfill cohorts: Cycle 1 (each cycle is 28 days) on Days 1, 2, 5, 6 and 8; Cycle 2 on Days 5 and 15 (day 15 only if 28 days schedule). Phase 2: Cycle 1 (Days 1 and 5), Cycle 2 (Day 5) and Cycle 3 or Cycle 4 (Day 5)
Area under the plasma concentration vs. time curve to infinity (AUCinf) of NMS-03305293 and possible identified metabolites (if appropriate) after multiple doses of drug.
Plasma samples will be collected and used for pharmacokinetics assessments
Measured: Phase 1 and backfill cohorts: Cycle 1 (each cycle is 28 days) on Days 1, 2, 5, 6 and 8; Cycle 2 on Days 5 and 15 (day 15 only if 28 days schedule). Phase 2: Cycle 1 (Days 1 and 5), Cycle 2 (Day 5) and Cycle 3 or Cycle 4 (Day 5)
Accumulation ratio (Rac) of NMS-03305293 and possible identified metabolites (if appropriate) after multiple doses of drug.
Plasma samples will be collected and used for pharmacokinetics assessments
Measured: Phase 1 and backfill cohorts: Cycle 1 (each cycle is 28 days) on Days 1, 2, 5, 6 and 8; Cycle 2 on Days 5 and 15 (day 15 only if 28 days schedule). Phase 2: Cycle 1 (Days 1 and 5), Cycle 2 (Day 5) and Cycle 3 or Cycle 4 (Day 5)
Oral plasma clearance (CL/F) of NMS-03305293 and possible identified metabolites (if appropriate) after multiple doses of drug
Plasma samples will be collected and used for pharmacokinetics assessments
Measured: Phase 1 and backfill cohorts: Cycle 1 (each cycle is 28 days) on Days 1, 2, 5, 6 and 8; Cycle 2 on Days 5 and 15 (day 15 only if 28 days schedule). Phase 2: Cycle 1 (Days 1 and 5), Cycle 2 (Day 5) and Cycle 3 or Cycle 4 (Day 5)
Apparent volume of distribution (Vd/F) of NMS-03305293 and possible identified metabolites (if appropriate) after multiple doses of drug
Plasma samples will be collected and used for pharmacokinetics assessments
Measured: Phase 1 and backfill cohorts: Cycle 1 (each cycle is 28 days) on Days 1, 2, 5, 6 and 8; Cycle 2 on Days 5 and 15 (day 15 only if 28 days schedule). Phase 2: Cycle 1 (Days 1 and 5), Cycle 2 (Day 5) and Cycle 3 or Cycle 4 (Day 5)
Phase 1: Renal clearance of NMS-03305293 and possible identified metabolites (if appropriate) after multiple doses of drug
Urine samples will be collected in patients treated in the phase 1 and in backfill cohorts and used for pharmacokinetics assessments
Measured: At baseline, at Cycle 1 (each cycle is 28 days) Day 5 at different timepoints
Phase 1: Cumulative amount recovered unchanged in the urine (Ae) of NMS-03305293 and possible identified metabolites (if appropriate) after multiple doses of drug
Urine samples will be collected in patients treated in the phase 1 and in backfill cohorts and used for pharmacokinetics assessments
Measured: At baseline, at Cycle 1 (each cycle is 28 days) Day 5 at different timepoints
Phase 1: Cumulative amount recovered unchanged in the urine expressed as a fraction of administered dose (Ae%) of NMS-03305293 and possible identified metabolites (if appropriate) after multiple doses of drug
Urine samples will be collected in patients treated in the phase 1 and in backfill cohorts and used for pharmacokinetics assessments
Measured: At baseline, at Cycle 1 (each cycle is 28 days) Day 5 at different timepoints.
Phase 1: Objective Tumor Response
Complete and partial responses will be assessed according to RANO criteria
Measured: At baseline, every 8 weeks until disease progression or start of a new anticancer therapy (approximately 18 months).
Phase 1: Duration of Response
Duration of response will be calculated from the date of either first CR or PR until the date of documented progression for patients who achieved CR or PR. Patients who died without report of progression will be considered non-events and censored at their last disease-free assessment date
Measured: From the date of first response up to data cut-off (approximately 18 months).
Phase 1: Progression Free Survival
Progression Free Survival will be calculated from the date of treatment initiation to the date of first documentation of disease progression, or death due to any cause, whichever occurs first
Measured: From the date of treatment initiation up to data cut-off (approximately 18 months)
Phase 2: Duration of response (DoR) through central retrospective assessment of RANO criteria
Duration of response will be calculated from the date of either first CR or PR until the date of documented progression for patients who achieved CR or PR. Patients who died without report of progression will be considered non-events and censored at their last disease-free assessment date
Measured: From the date of first response up to data cut-off (approximately 18 months).
Phase 2: Progression-free survival (PFS)
Progression Free Survival will be calculated from the date of treatment initiation to the date of first documentation of disease progression, or death due to any cause, whichever occurs first
Measured: From the date of treatment initiation up to data cut-off (approximately 18 months)
Phase 2: 6-month PFS Rate
Percentage of patients progressive-free at 6 months from treatment initiation
Measured: From date of treatment initiation until the date of first documentation of progression or death for any cause, whichever occurs first, assessed up to 6 months
Phase 2: 9 and 12-Months Overall Survival Rates
Percentage of patients alive at 9 and 12 months from treatment initiation.
Measured: From the date of treatment initiation until the date of death from any cause, assessed up to 9 and 12 months.
Overall Survival
Overall Survival will be calculated from the date of treatment initiation to the date of death due to any cause
Measured: From the date of treatment initiation up to data cut-off (approximately 24 months)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Jun 2021
- Study start1 Dec 2021
- Primary completion30 May 2027 (estimated)
- Study completion7 Sep 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for GlioblastomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 150 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Nerviano Medical Sciences
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04910022
- Sponsor's protocol ID
- PARPA-293-002
- Other IDs
- 2020-003417-35, 2023-508318-41-00, 2023
- Status last verified
- Aug 2025
- First submitted
- 21 May 2021
- Last updated
- 19 Aug 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 19 Aug 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I/II Combination Study of NMS-03305293 and Temozolomide in Adult Patients With Recurrent Glioblastoma
- ClinicalTrials.gov ID
- NCT04910022
- Acronym / sponsor ID
- PARPA-293-002
- Conditions
- Glioblastoma, Diffuse Glioma
- Keywords
- IDH wild type, PARP inhibitor
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 150 participants (estimated)
- Lead sponsor
- Nerviano Medical SciencesIndustry (pharma, biotech, devices)
- Study start
- 1 Dec 2021 (actual)
- Primary completion
- 30 May 2027 (estimated)
- Study completion
- 7 Sep 2027 (estimated)
- First posted
- 2 Jun 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| NMS-03305293 +TMZ | Experimental | Drug: NMS-03305293, Drug: TemozolomidePhase 1 Dose Escalation: All patients will receive NMS-03305293 and temozolomide (TMZ) administered orally (NMS-03305293 once or twice daily on days 1-7 or 28 consecutive days from Day 1 to Day 28; TMZ once daily on days 1-5;) in repeated 4-week cycles aimed at defining the Maximum Tolerated Dose (MTD) and the Recommended Phase 2 Doses (RP2Ds) of NMS-03305293 in combination with TMZ. Each cycle is 28 days. Phase 2: Once the RP2D is defined, the patients will receive TMZ daily on days 1-5 in combination with NMS-03305293 at the RP2D on days 1-7 or on days 1-28 every 28 days. Backfill cohorts: additional patients may be treated with TMZ daily on days 1-5 and NMS-03305293 at different dose levels/schedules that have been previously assessed and determined to be safe, in order to properly characterize the exposure relationship over a range of doses/schedules. The backfill cohorts may run in parallel. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (36 listed)
- Phase 1
- Backfill cohorts
- Phase 2
- Phase 1 (including backfill) and Phase 2
- 4. 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.
Key exclusion criteria (18 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| NMS-03305293Route of administration: Oral | Drug | NMS-03305293 +TMZ |
| TemozolomideRoute of administration: Oral Commercially available temozolomide | Drug | NMS-03305293 +TMZ |
Primary outcome
Phase 1: Number of Participants with first-cycle dose limiting toxicity
Time frame: 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
Phase 2: Objective Response Rate
Time frame: From the date of first response up to data cut-off (approximately 18 months)
Objective Response Rate (ORR), calculated as the proportion of evaluable patients who have achieved, as best overall response (BOR), confirmed complete response (CR) or partial response (PR) through central retrospective assessment of RANO criteria
20 secondary outcomes
Number of participants with Adverse Events (AEs)
Time frame: From the Informed Consent signature to 28 days after the last dose of study treatment administration
Maximum concentration (Cmax) of NMS-03305293 and possible identified metabolites (if appropriate) after single and multiple doses of drug
Time frame: Phase 1 and backfill cohorts: Cycle 1 (each cycle is 28 days) on Days 1, 2, 5, 6 and 8; Cycle 2 on Days 5 and 15 (day 15 only if 28 days schedule). Phase 2: Cycle 1 (Days 1 and 5), Cycle 2 (Day 5) and Cycle 3 or Cycle 4 (Day 5)
Time to observed Cmax (Tmax) of NMS-03305293 and possible identified metabolites (if appropriate) after single and multiple doses of drug
Time frame: Phase 1 and backfill cohorts: Cycle 1 (each cycle is 28 days) on Days 1, 2, 5, 6 and 8; Cycle 2 on Days 5 and 15 (day 15 only if 28 days schedule). Phase 2: Cycle 1 (Days 1 and 5), Cycle 2 (Day 5) and Cycle 3 or Cycle 4 (Day 5)
Area under the concentration-time curve up to the last detectable plasma concentration (AUClast) of NMS-03305293 and possible identified metabolites (if appropriate) after single and repeated dose of drug.
Time frame: Phase 1 and backfill cohorts: Cycle 1 (each cycle is 28 days) on Days 1, 2, 5, 6 and 8; Cycle 2 on Days 5 and 15 (day 15 only if 28 days schedule). Phase 2: Cycle 1 (Days 1 and 5), Cycle 2 (Day 5) and Cycle 3 or Cycle 4 (Day 5)
Terminal elimination half-life (t1/2) of NMS-03305293 and possible identified metabolites (if appropriate) after single and multiple doses of drug
Time frame: Phase 1 and backfill cohorts: Cycle 1 (each cycle is 28 days) on Days 1, 2, 5, 6 and 8; Cycle 2 on Days 5 and 15 (day 15 only if 28 days schedule). Phase 2: Cycle 1 (Days 1 and 5), Cycle 2 (Day 5) and Cycle 3 or Cycle 4 (Day 5)
Area under the plasma concentration vs. time curve to infinity (AUCinf) of NMS-03305293 and possible identified metabolites (if appropriate) after multiple doses of drug.
Time frame: Phase 1 and backfill cohorts: Cycle 1 (each cycle is 28 days) on Days 1, 2, 5, 6 and 8; Cycle 2 on Days 5 and 15 (day 15 only if 28 days schedule). Phase 2: Cycle 1 (Days 1 and 5), Cycle 2 (Day 5) and Cycle 3 or Cycle 4 (Day 5)
Accumulation ratio (Rac) of NMS-03305293 and possible identified metabolites (if appropriate) after multiple doses of drug.
Time frame: Phase 1 and backfill cohorts: Cycle 1 (each cycle is 28 days) on Days 1, 2, 5, 6 and 8; Cycle 2 on Days 5 and 15 (day 15 only if 28 days schedule). Phase 2: Cycle 1 (Days 1 and 5), Cycle 2 (Day 5) and Cycle 3 or Cycle 4 (Day 5)
Oral plasma clearance (CL/F) of NMS-03305293 and possible identified metabolites (if appropriate) after multiple doses of drug
Time frame: Phase 1 and backfill cohorts: Cycle 1 (each cycle is 28 days) on Days 1, 2, 5, 6 and 8; Cycle 2 on Days 5 and 15 (day 15 only if 28 days schedule). Phase 2: Cycle 1 (Days 1 and 5), Cycle 2 (Day 5) and Cycle 3 or Cycle 4 (Day 5)
Apparent volume of distribution (Vd/F) of NMS-03305293 and possible identified metabolites (if appropriate) after multiple doses of drug
Time frame: Phase 1 and backfill cohorts: Cycle 1 (each cycle is 28 days) on Days 1, 2, 5, 6 and 8; Cycle 2 on Days 5 and 15 (day 15 only if 28 days schedule). Phase 2: Cycle 1 (Days 1 and 5), Cycle 2 (Day 5) and Cycle 3 or Cycle 4 (Day 5)
Phase 1: Renal clearance of NMS-03305293 and possible identified metabolites (if appropriate) after multiple doses of drug
Time frame: At baseline, at Cycle 1 (each cycle is 28 days) Day 5 at different timepoints
Phase 1: Cumulative amount recovered unchanged in the urine (Ae) of NMS-03305293 and possible identified metabolites (if appropriate) after multiple doses of drug
Time frame: At baseline, at Cycle 1 (each cycle is 28 days) Day 5 at different timepoints
Phase 1: Cumulative amount recovered unchanged in the urine expressed as a fraction of administered dose (Ae%) of NMS-03305293 and possible identified metabolites (if appropriate) after multiple doses of drug
Time frame: At baseline, at Cycle 1 (each cycle is 28 days) Day 5 at different timepoints.
Phase 1: Objective Tumor Response
Time frame: At baseline, every 8 weeks until disease progression or start of a new anticancer therapy (approximately 18 months).
Phase 1: Duration of Response
Time frame: From the date of first response up to data cut-off (approximately 18 months).
Phase 1: Progression Free Survival
Time frame: From the date of treatment initiation up to data cut-off (approximately 18 months)
Phase 2: Duration of response (DoR) through central retrospective assessment of RANO criteria
Time frame: From the date of first response up to data cut-off (approximately 18 months).
Phase 2: Progression-free survival (PFS)
Time frame: From the date of treatment initiation up to data cut-off (approximately 18 months)
Phase 2: 6-month PFS Rate
Time frame: From date of treatment initiation until the date of first documentation of progression or death for any cause, whichever occurs first, assessed up to 6 months
Phase 2: 9 and 12-Months Overall Survival Rates
Time frame: From the date of treatment initiation until the date of death from any cause, assessed up to 9 and 12 months.
Overall Survival
Time frame: From the date of treatment initiation up to data cut-off (approximately 24 months)
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Aug 2025.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
18 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing NMS-03305293 and Temozolomide in people with Glioblastoma and Diffuse Glioma, run by Nerviano Medical Sciences at 18 sites in 5 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 36 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 19 Aug 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 18 sites in United States, Italy, Netherlands, Puerto Rico, Switzerland. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Phase 1: Number of Participants with first-cycle dose limiting toxicity (time frame: 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). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Aug 2025.