Reirradiation and Niraparib in Patients With Recurrent Glioblastoma

NCT05666349 | Withdrawn Phase 1 DMC

• 2 other identifiers: UCL/1422862022-001706-22
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief 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). 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). 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.

Conditions

Recurrent Glioblastoma

Keywords

Niraparib; Glioblastoma; Re-irradiation

Outcome Measures

Primary Outcomes (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.

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

Secondary Outcomes (9)

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

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

• Overall survival (OS)

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

• Progression-free survival (PFS)

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

• Best Overall Objective Response Rate

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

• Time to treatment failure (TTF)

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

Study Arms (1)

Niraparib and re-irradiation (re-RT)

EXPERIMENTAL

Patients 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.

Drug: Niraparib; Radiation: Re-irradiation (re-RT)

Interventions

Niraparib DRUG

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

Also known as: Zejula

Niraparib and re-irradiation (re-RT)

Re-irradiation (re-RT) RADIATION

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

Niraparib and re-irradiation (re-RT)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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%
• 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

You may not qualify if:

• 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
• 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)

Sponsors & Collaborators

• University College, London: lead
• GlaxoSmithKline: collaborator

Related Links

• Cancer Research UK \& UCL Cancer Trials Centre

MeSH Terms

Conditions

Glioblastoma

Interventions

niraparib; Re-Irradiation

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Radiotherapy; Therapeutics; Retreatment

Study Officials

• Dusan Milanovic

  The Christie NHS Foundation Trust

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 2, 2022
• First Posted: December 27, 2022
• Study Start: October 13, 2023
• Primary Completion: October 13, 2023
• Study Completion: October 13, 2023
• Last Updated: March 26, 2024

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will not share