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Recurrent GlioblastomaPhase 1RiNGNCT05666349

Reirradiation and Niraparib in Patients With Recurrent Glioblastoma

A Phase 1 study testing Niraparib and Re-irradiation (re-RT) in people with Recurrent Glioblastoma, run by University College, London.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial summary

The goal of this clinical trial is to investigate a drug called niraparib in patients with glioblastoma that was previously treated but has returned (called recurrent glioblastoma, or rGBM). Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Recurrent Glioblastoma
What is being tested?
Niraparib and Re-irradiation (re-RT)
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
No sites listed yet
Study dates
13 Oct 2023to 13 Oct 2023
Phase
Phase 1
Are there results?
None posted in the registry

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

  • Local recurrence of GBM which can be resected or which is not amenable for surgical resection. Patients who have had surgery may also be included if there is residual enhancing disease on the immediate post-operative MRI or if enhancing disease develops on subsequent follow-up imaging
  • Recurrent tumour visible on MRI-T1-Gd with the diameter measuring ≤6cm
  • Prior history of standard dose, conventionally fractionated CNS radiotherapy (i.e. 54-60Gy in 28-33 fractions)
  • At least 6 months since the end of pre-irradiation
  • < 2 prior lines of chemotherapy
  • Karnofsky Performance Score (KPS) ≥ 70%
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  • Age ≥ 18 years
  • Written informed consent
  • Adequate organ and marrow function as defined below:
  • absolute neutrophil count ≥ 1.5x109/L
  • platelets ≥ 100 x109/L
  • haemoglobin > 9.0 g/dL
  • total bilirubin ≤ 1.5 x upper limit of normal (ULN) (≤2.0 in patients with known Gilbert's syndrome) OR direct bilirubin ≤ 1 x ULN
  • Aspartate or alanine transferase (AST or ALT) ≤2.5 x ULN
  • Serum creatinine ≤ 1.5 x upper limit of normal (ULN) or calculated creatinine clearance ≥ 30 mL/min using the Cockcroft-Gault equation
  • Negative serum or urine pregnancy test for women of childbearing potential (WOCBP)
  • Willing to comply with the contraceptive requirements of the trial (see section 6.3 of protocol for details)
  • Patients receiving corticosteroids may continue to receive them as long as their dose is stable (i.e. not increased by >2mg) for at least 1-2 weeks prior to initiating protocol therapy
  • Agree to not donate blood during trial treatment or for 90 days after the last dose of niraparib
  • Normal blood pressure or adequately treated and controlled hypertension

Who cannot join

  • Concurrent participation in another interventional clinical trial
  • Tumour progression or recurrence within 3 months of initial concurrent chemoradiation
  • Heart failure (compensate or decompensate)
  • Previous treatment with PARP inhibitors
  • Previous treatment with re-RT
  • Women who are pregnant or breast feeding or plan to breastfeed during trial treatment or for 30 days after the last dose of niraparib
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  • Major surgical procedure within 3 weeks prior to the first dose niraparib. Note: Patient must have recovered from any surgical effects before the first dose of niraparib
  • Received any investigational therapy within 4 weeks prior to, or within a time interval less than at least 5 half-lives of the investigational agent, whichever is shorter, the first dose of niraparib
  • Known hypersensitivity to niraparib components or excipients
  • Received a transfusion (platelets or red blood cells) within 4 weeks prior to the first dose of niraparib
  • Received colony stimulating factors (e.g., granulocyte colony-stimulating factor, granulocyte macrophage colony stimulating factor, or recombinant erythropoietin) within 4 weeks prior to the first dose of niraparib
  • Known history of Grade 3 or 4 anemia, neutropenia or thrombocytopenia due to prior chemotherapy that persisted > 4 weeks and was related to the most recent treatment
  • Known history of myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML)
  • Known history of a serious, uncontrolled medical disorder, nonmalignant systemic disease, or active, uncontrolled infection. Examples include, but are not limited to, uncontrolled ventricular arrhythmia, recent (within 90 days of registration) myocardial infarction, uncontrolled major seizure disorder, unstable spinal cord compression, superior vena cava syndrome, or any psychiatric disorder that prohibits obtaining informed consent
  • Prior malignancy (known diagnosis, detection, or treatment of another type of cancer) within 2 years prior to the first dose of niraparib (except basal or squamous cell carcinoma of the skin and cervical cancer that has been definitively treated)
  • Known leptomeningeal disease, multifocal GBM, or radiologic signs of CNS hemorrhage
  • Known active hepatitis B (e.g., hepatitis B surface antigen [HBsAg] reactive) or hepatitis C (e.g., hepatitis C virus [HCV] ribonucleic acid [qualitative] is detected) infections
  • Live vaccines within 30 days prior to the first dose of niraparib while participating in this clinical study
  • If being considered for 300mg dose only:
  • patient weight <77Kg
  • platelet count of <150 x 109/L
  • Patient is immunocompromised. Patients with splenectomy are not excluded. Patients with known human immunodeficiency virus (HIV) are not excluded if they meet the following criteria:
  • Cluster of differentiation 4 (CD4) ≥350/μL and viral load <400 copies/mL
  • No history of acquired immunodeficiency syndrome-defining opportunistic infections within 12 months prior to enrolment.
  • No history of HIV-associated malignancy for the past 5 years.
  • Concurrent antiretroviral therapy as per the most current National Institutes of Health (NIH) Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents Living with HIV [NIH, 2021] started <4 weeks prior to study enrolment.

About this study

Official title: Reirradiation (Re-RT) and Niraparib (NIRA) in Patients With Recurrent Glioblastoma (rGBM)

The goal of this clinical trial is to investigate a drug called niraparib in patients with glioblastoma that was previously treated but has returned (called recurrent glioblastoma, or rGBM).

Through this study, investigators would like to find out the best dose of niraparib to give to treat the disease when given together with radiotherapy (known in this study as reirradiation, or re-RT).

Read more

Patients receive 10 doses of reirradiation over approximately 2 weeks. At the same time, niraparib capsules are taken orally at home, every day. Niraparib treatment continues until the patient is required to stop either because the treatment stops working or because of side-effects.

Participants will come into clinic weekly for blood tests and clinical examinations in the first month of treatment. After this, the assessments will be done monthly.

Once the patient has finished niraparib treatment, the patient will enter follow-up and be seen once a year to see if there are any late side-effects from trial treatment, how the disease is doing, and if further treatments have been received for it. This follow-up continues until the end of the trial.

Being tested
Niraparib, Re-irradiation (re-RT)
Keywords
Niraparib, Glioblastoma, Re-irradiation
Medical subject headings
Glioblastoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • NiraparibDrug

    Also called Zejula

    100 mg, 200 mg, or 300mg oral niraparib once daily.

  • Re-irradiation (re-RT)Radiation

    Intensity modulated radiotherapy (IMRT)-based re-RT for a total dose of 35 Gy in 10 daily fractions.

Study groups in NCT05666349
Study groupRoleWhat they receive
Niraparib and re-irradiation (re-RT)ExperimentalPatients will be treated with IMRT-based re-RT for a total dose of 35 Gy in 10 daily fractions over approx. 2 weeks. Patients will take niraparib daily from the first day of re-RT until documented progression or discontinuation due to unacceptable treatment-related toxicity or any other cause (whichever occurs sooner). Patients will be recruited in cohorts of 3. Following the completion of each dosing cohort and once the patients have completed the dose limiting toxicity (DLT) assessment window, the independent data monitoring committee (IDMC) will review the data for each patient. In conjunction with the statistical recommendations from the continual reassessment method (CRM), the IDMC will advise whether the dose for the next cohort should be escalated, de-escalated or stay at the current niraparib dose.
Receives: Drug: Niraparib; Radiation: Re-irradiation (re-RT)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Dose limiting toxicity (DLT) as assessed by CTCAE v5.0

    DLTs will be assessed in order to determine the maximum tolerated dose of niraparib given concurrently with re-RT.

    Measured: DLTs with an onset date within the first cycle of treatment (typically 28 days) will be assessed.

Secondary outcomes (9)

  1. Safety and tolerability of niraparib given concurrently with re-RT.

    Safety and tolerability of niraparib given concurrently with re-RT, characterised in terms of adverse events as assessed by CTCAE v5.0.

    Measured: Adverse events will be reported until 30 calendar days post last niraparib and/or post last investigational treatment (re-RT) administration.

  2. Overall survival (OS)

    Death

    Measured: From trial treatment start date until date of death, assessed at 9 months

  3. Progression-free survival (PFS)

    Disease progression or death

    Measured: From trial treatment start date until disease progression or death, whichever occurs first, assessed up to 9 months.

  4. Best Overall Objective Response Rate

    Frequency and percentage of patients who experienced a Complete Response (CR), Partial Response (PR), Stable Disease (SD) and Progressive Disease (PD)

    Measured: From trial treatment start date through to end of trial, assessed at 12 months

  5. Time to treatment failure (TTF)

    Treatment failure classified as early treatment discontinuation, progression, starting further treatment or death.

    Measured: From trial treatment start date until early treatment discontinuation, progression, starting further treatment or death, whichever occurs first assessed up to 9 months.

  6. Duration on Treatment

    Median time on trial treatment will be presented.

    Measured: From trial treatment start date until treatment discontinuation, assessed at 12 months

  7. Treatment Compliance

    Reasons for treatment delays, dose omissions, dose reductions and treatment discontinuation.

    Measured: From trial treatment start date until treatment discontinuation, assessed at 12 months

  8. Health-related Quality of life (HRQoL): QLQ-C30

    HRQoL assessed by European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30, scored according to EORTC manual guideline. Score range is 0-100, with 100 being the highest response level.

    Measured: From screening up to 9 months, at specific time points

  9. Health-related Quality of life (HRQoL): QLQ-BN20

    HRQoL assessed by European Organisation for Research and Treatment of Cancer (EORTC) QLQ-BN20, scored according to EORTC manual guidelines.

    Measured: From screening up to 9 months, at specific time points

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted27 Dec 2022
  2. Study start13 Oct 2023
  3. Primary completion13 Oct 2023
  4. Study completion13 Oct 2023

Why it stopped: Funder support withdrawn 13-Oct-2023. Study did not open to recruitment.

Resources

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
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05666349
Sponsor's protocol ID
UCL/142286
Other IDs
2022-001706-22
Acronym
RiNG
Status last verified
Mar 2024
First submitted
2 Nov 2022
Last updated
26 Mar 2024
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Niraparib and Re-irradiation (re-RT) in people with Recurrent Glioblastoma, run by University College, London.

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 20 inclusion and 26 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: withdrawn, as of the sponsor's last update on 26 Mar 2024. Status can change between updates, so confirm with the study contact before making plans.

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 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.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was withdrawn before enrolling participants, so there are no results.

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?

Dose limiting toxicity (DLT) as assessed by CTCAE v5.0 (time frame: DLTs with an onset date within the first cycle of treatment (typically 28 days) will be assessed.). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05666349.

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 26 Mar 2024.

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