A Study Evaluating the Association of Hypofractionated Stereotactic Radiation Therapy and Durvalumab for Patients With Recurrent Glioblastoma

NCT02866747 | Completed Phase 1 DMC

• 1 other identifier: 16TETE04
• Study Type: interventional
• Target: 108
• Locations: 1 country
• Sites: 10

Brief Summary

This study is a phase I/II, national, multicenter, open-label study starting with a Phase I part followed by a Phase II part. The phase I part of the study aims to evaluate the safety of the association of hypofractionated stereotactic radiation therapy (hFSRT) and the anti-PD-L1 Durvalumab immunotherapy in patients with recurrent glioblastoma. A maximum number of 12 patients will be enrolled in this phase I part. Once the recommended combination schema will be declared, patients will be enrolled in the Phase II part of the study in order to evaluate the efficacy (overall survival) of the combined treatment in recurrent glioblastoma. In this Phase II part, 100 patients will be assigned by randomization to one of the two following arms:

• Arm A (control arm): Radiation therapy alone
• Arm B (Experimental arm): Combined treatment with Anti-PD-L1 Durvalumab

Conditions

Glioblastoma

Outcome Measures

Primary Outcomes (2)

• Phase I: Dose Limiting Toxicities (DLT) incidence

  For each patient of the phase I part, DLT incidence will be evaluated until one month after the last radiotherapy fraction.

  8 months

• Phase II: overall survival

  36 months post randomization

Secondary Outcomes (10)

• Phase I and II: Intracranial progression-free interval

  27 months

• Phase I: Safety and tolerability according to the classification of the National Cancer Institute Common Toxicity Criteria for Adverse Effects (NCI-CTCAE) version 4.03

  19 months

• Phase I and II: Quality of life using the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life questionnaire (QLQ C30).

  27 months

• Phase I and II : Quality of life using the using the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Brain Neoplasm (QLQ-BN20).

  27 months

• Phase I and II: Neurologic and neurocognitive functions using Neurologic Assessment in Neuro-Oncology (NANO) scale.

  27 months

Study Arms (2)

Arm A: radiation therapy alone

ACTIVE COMPARATOR

Hypofractionated stereotactic radiation therapy (hFSRT) 24 Gray (Gy), 8 Gy per fraction preferentially at 80% isodose (60 to 90 % accepted), 3 fractions scheduled on Day 1 of the radiotherapy (RT), Day 3 RT and Day 5 RT.

Radiation: Hypofractionated stereotactic radiation therapy

Arm B: combined treatment

EXPERIMENTAL

hFSRT 24 Gy, 8 Gy per fraction preferentially at 80% isodose (60 to 90 % accepted), 3 fractions scheduled on Day 1 RT, Day 3 RT and Day 5 RT, combined with Durvalumab infusion: first administration of Durvalumab\* on Day 5 RT (i.e. the same day after the last fraction of radiation, corresponding to the Day 1 for Durvalumab treatment) and then administration of Durvalumab 1500 milligrams (mg) every four weeks. \* Dosing 750 mg or 1500 mg, according to the recommended combination schema determined in phase I.

Radiation: Hypofractionated stereotactic radiation therapy; Drug: Durvalumab

Interventions

Hypofractionated stereotactic radiation therapy RADIATION

Arm A: radiation therapy alone; Arm B: combined treatment

Durvalumab DRUG

Arm B: combined treatment

Eligibility Criteria

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

You may qualify if:

• Age ≥ 18 years at time of study entry.
• Previous histopathologic confirmation of glioblastoma.
• Any line of recurrence of glioblastoma proven by contrast enhanced MRI within 28 days prior to the first fraction of RT, per modified RANO criteria (Wen et al JCO 2010).
• Note: Recurrence is defined as progression following therapy (i.e., chemotherapy, radiation, second surgery).
• Recurrent nodule of an histologically confirmed diagnosis of World Health Organization (WHO) Grade IV malignant glioma (Glioblastoma) occurring in or out the previous irradiation fields.
• Recurrent disease documented by MRI evidence with a size of the recurrence evaluated on T1 post-gadolinium sequence ≤35mm.
• Patient for which a re-irradiation (by hFSRT) has been decided by the multidisciplinary medical board.
• Patients with measurable disease.
• Prior radiotherapy must be ended at least 12 weeks before the first fraction of RT (unless progressive disease outside of the radiation field or histopathologic confirmation of unequivocal tumor to eliminate pseudoprogression images according to RANO recommendations, Wen et al JCO 2010).
• In case of previous anti-VEGF/VEGFR targeted therapy: at least 28 days between the last injection of anti-VEGF/VEGFR targeted therapy and the first fraction of RT.
• Karnofsky performance status ≥70.
• Adequate hematologic, renal and hepatic function, as defined below:
• Absolute Neutrophil Count ≥ 1500/mm3
• Haemoglobin ≥ 9.0 g/dL
• Platelet count ≥ 100,000/mm3

You may not qualify if:

• Multifocal GBM recurrence (exception: multisite nodular recurrence (maximum: 2 sites) that can be irradiated by hFSRT according to investigator's judgement).
• Distance between tumor and optic ways including chiasma or brainstem \<1 cm.
• Prior re-irradiation (except if fulfilling the following requirements: ended at least 6 months before the first fraction of RT in the study, localized outside the target of interest for the trial, and previously re-irradiated lesion controlled at the time of study entry).
• Prior exposure to Durvalumab or other anti-PD-1, anti-PD-L1, anti-CTLA4 antibodies.
• Patient who received a live vaccine within 30 days prior to the first fraction of RT.
• Receipt of the last dose of anti-cancer therapy (chemotherapy, immunotherapy, endocrine therapy, targeted therapy, biologic therapy, tumor embolization, monoclonal antibodies, other investigational agent) within 28 days prior to the first fraction of RT.
• Current or prior use of immunosuppressive medication within 10 days before the first fraction of RT (exception: systemic corticosteroids at physiologic doses not exceeding 10 mg/day of prednisone or equivalent are allowed as well as steroids as premedication for hypersensitivity reactions (eg, CT scan premedication) - Topical, inhaled, nasal and ophthalmic steroids are not prohibited).
• Mean QT interval corrected for heart rate (QTc) ≥470 ms calculated from 3 electrocardiograms (ECGs) using Fridericia's Correction
• Presence of diffuse leptomeningeal disease or extracranial disease.
• Active suspected or prior documented autoimmune disease (including inflammatory bowel disease, celiac disease, Wegener's granulomatosis and Hashimoto's thyroiditis).
• Note: participants with vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger, are permitted to enroll.
• Known primary immunodeficiency or active HIV.
• Known active or chronic viral hepatitis or history of any type of hepatitis within the last 6 months indicated by positive test for hepatitis B surface antigen (HBV sAG) or hepatitis C virus antibody.
• History of organ transplant requiring use of immunosuppressive medication.
• History of active tuberculosis.

Sponsors & Collaborators

• AstraZeneca: collaborator
• Institut Claudius Regaud: lead

Study Sites (10)

Institut de Cancerologie de L'Ouest

Angers, 49055, France

Location

Hopital Avicenne

Bobigny, 93 000, France

Location

Centre Francois Baclesse

Caen, 14 000, France

Location

Centre Georges Francois Leclerc

Dijon, 21 000, France

Location

Institut Regional Du Cancer de Montpellier

Montpellier, 34 298, France

Location

Hopital Pitie Salpetriere

Paris, 75013, France

Location

Institut Curie

Saint-Cloud, 92 210, France

Location

Centre Paul Strauss

Strasbourg, 67000, France

Location

Institut Claudius Regaud

Toulouse, France

Location

Institut Gustave Roussy

Villejuif, 94 800, France

Location

Related Publications (1)

• Pouessel D, Ken S, Gouaze-Andersson V, Piram L, Mervoyer A, Larrieu-Ciron D, Cabarrou B, Lusque A, Robert M, Frenel JS, Uro-Coste E, Olivier P, Mounier M, Sabatini U, Sanchez EH, Zouitine M, Berjaoui A, Cohen-Jonathan Moyal E. Hypofractionated Stereotactic Re-irradiation and Anti-PDL1 Durvalumab Combination in Recurrent Glioblastoma: STERIMGLI Phase I Results. Oncologist. 2023 Sep 7;28(9):825-e817. doi: 10.1093/oncolo/oyad095.

  PMID: 37196069 RESULT

MeSH Terms

Conditions

Glioblastoma

Interventions

durvalumab

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

Study Design

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

Study Record Dates

• First Submitted: August 5, 2016
• First Posted: August 15, 2016
• Study Start: January 17, 2017
• Primary Completion: November 2, 2024
• Study Completion: November 2, 2024
• Last Updated: April 14, 2026

Record last verified: 2026-04

Locations

FR (10)