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Niraparib and Temozolomide in Patients Glioblastoma

ConditionGlioma, Malignant
Trial statusNot yet recruiting
Trial phasePhase 1, Phase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorArmando Santoro, MD

About this trial

The study evaluates safety, tolerability, pharmacokinetics at recommended phase II dose (RP2D) and preliminary antitumor activity of Niraparib + dd-TMZ "one week on, one week off" in patients affected by recurrent GBM IDH wild-type and recurrent IDH mutant (WHO grade 2-4) gliomas.

The treatment will be administered until progressive disease, unacceptable toxicity, consent withdrawal, lost to follow-up or death.

The entire study is expected to last approximately 40 months.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

At least 18 years of age.

Ability to understand and willingness to sign an ethics committee approved written informed consent document (or that of legally authorized representative, if applicable).

Patients with diagnosis of recurrent\progressive IDH wild-type GBM (WHO 2021, grade 4). All the GBM histological variants are allowed.

Patients with diagnosis of recurrent/progressive IDH mutant gliomas (WHO 2021, grade 2-4). Both astrocytoma and oligodendroglioma may be included.

Disqualifiers

Any serious or uncontrolled medical disorder that, in the opinion of the investigator, may increase the risk associated with study participation or study drug administration, impair the ability of the subject to receive the planned therapy (including brain surgery), or interfere with the interpretation of study results.

Anticancer treatment within the last 14 days before the start of trial treatment, for example chemotherapy, radiotherapy, immunotherapy. A shorter interval can be approved by the principal investigator, if deemed appropriate.

Previous G4 hematological toxicity (anemia, neutropenia, thrombocytopenia) during concomitant and/or adjuvant TMZ treatment.

Previous treatment with a PARP inhibitor.

Trial design

Design model

Sequential

Treatments tested in this trial

  • Temodal

    Drug

    given orally for 7 consecutive days, followed by 7 days OFF, in a cycle of 28 days

  • Niraparib

    Drug

    given orally in continous

Treatment groups

86 Participants
are divided into 6 treatment groups

6

Treatment groups

See each treatment group below.

Group A: Niraparib + Temodal Level 0Experimental treatment 2 interventions
Group B: Niraparib + Temodal Level 1Experimental treatment 2 interventions
Group C: Niraparib + Temodal Level 2Experimental treatment 2 interventions
Group D: Niraparib + Temodal Level 3Experimental treatment 2 interventions
Group E: Niraparib + Temodal Level -1Experimental treatment 2 interventions
Group F: Niraparib + Temodal Expansion PhaseExperimental treatment 2 interventions

Trial outcomes

Primary outcomes

1

Escalation Phase : maximum tolerated dose (MTD)

To determine the MTD of the combination of dd-TMZ and Niraparib, established in the first cycle of therapy, in order to determine the recommended phase II dose (RP2D).

Time frame
1 year
2

Expansion Phase : PFS

To assess the proportion of patients progression-free at 6 months for recurrent IDH wild-type glioblastoma (Cohort 1) and at 8 months for recurrent IDH-mutant lower-grade gliomas (Cohort 2)

Time frame
8 months

Secondary outcomes

1

pharmacokinetics CMAX

To evaluate the pharmacokinetics proprieties of the combination of dd-TMZ and Niraparib given on a 7d ON/7d OFF schedule at specific time-points during experimental treatment.Niraparib given on a 7d ON/7d OFF schedule

Time frame
1 year
2

cerebrospinal fluid drug concentration

To evaluate cerebrospinal fluid (CSF) drug concentration of the combination of dd-TMZ and Niraparib given on a 7d ON/7d OFF schedule in those cases where it is safely feasible collecting liquor samples through lumbar puncture and only after patient's appropriate consent.

Time frame
1 year
3

Adverse event monitoring

To assess the safety and tolerability of the combination of dd-TMZ and Niraparib given at the RP2D on a 7d ON/7d OFF schedule

Time frame
2 years
4

tumour tissue drug concentration

To evaluate tissue drug concentration schedule and visualized intra-tumor distribution by mass spectrometry imaging in surgical specimen of the combination of dd-TMZ and Niraparib given on a 7d ON/7d OFF from patients who need second surgery after patient's consent.

Time frame
2 years

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Armando Santoro, MD

Lead sponsor

Istituto Clinico Humanitas

Sponsor institution

Istituto Clinico Humanitas

Collaborator

GlaxoSmithKline

Collaborator

Source ClinicalTrials.gov

This trial is not recruiting at the moment. You can still explore other options: