Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02866747
Recruitment Status : Suspended (Interim analysis)
First Posted : August 15, 2016
Last Update Posted : August 9, 2019
Sponsor:
Collaborator:
AstraZeneca
Information provided by (Responsible Party):
Institut Claudius Regaud

Tracking Information
First Submitted Date  ICMJE August 5, 2016
First Posted Date  ICMJE August 15, 2016
Last Update Posted Date August 9, 2019
Actual Study Start Date  ICMJE January 17, 2017
Estimated Primary Completion Date April 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 10, 2016)
  • Phase I: Dose Limiting Toxicities (DLT) incidence [ Time Frame: 8 months ]
    For each patient of the phase I part, DLT incidence will be evaluated until one month after the last radiotherapy fraction.
  • Phase II: Rate of patient without local progression of the irradiated tumor according to the Response Assessment in Neuro-Oncology (RANO) criteria at 6 months post randomization. [ Time Frame: 6 months post randomization ]
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT02866747 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: August 10, 2016)
  • Phase I and II: Intracranial progression-free interval [ Time Frame: 27 months ]
    Intracranial progression-free interval is defined by the time from inclusion (for phase I) or randomization (for phase II) to local or distant (outside the re-irradiated volume) progression. Patients without progression at last follow-up news are censored at this date.
  • Phase I and II: Overall survival [ Time Frame: 30 months ]
    Overall survival is defined as the time from inclusion (for phase I) or randomization (for phase II) to death from any cause. Patients alive at last follow-up news are censored at this date.
  • 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 [ Time Frame: 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). [ Time Frame: 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). [ Time Frame: 27 months ]
  • Phase I and II: Neurologic and neurocognitive functions using Neurologic Assessment in Neuro-Oncology (NANO) scale. [ Time Frame: 27 months ]
  • Phase I and II: Neurologic and neurocognitive functions using Neurologic Assessment in Montreal Cognitive Assessment (MoCA) tests. [ Time Frame: 27 months ]
  • Phase II: Time to Quality of Life (QoL) deterioration. [ Time Frame: 27 months ]
    Time to QoL deterioration is defined as the time interval between randomization and first decrease in QoL score greater or equal to 5 points. Patients without such a QoL decrease will be censored at last follow-up news or at initiation of a new therapeutic strategy.
  • Phase II: time to neurocognitive deterioration [ Time Frame: 27 months ]
    Time to neurocognitive deterioration is defined as the time interval between randomization and first of 3 points difference in MoCA as minimal clinically important difference. Patients without such a neurocognitive decrease will be censored at last follow-up news or at initiation of a new therapeutic strategy.
  • Phase II: Immune-related intracranial progression-free interval [ Time Frame: 27 months ]
    Immune-related intracranial progression-free interval is defined by the time from randomization to local or distant (outside the re-irradiated volume) progression (based on immunotherapy Response Assessment for Neuro-Oncology iRANO). Patients without progression at last follow-up news are censored at this date.
  • Phase II: Acute and late toxicities according to the classification of the National Cancer Institute Common Toxicity Criteria for Adverse Effects (NCI-CTCAE) version 4.03 [ Time Frame: 27 months ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study Evaluating the Association of Hypofractionated Stereotactic Radiation Therapy and Durvalumab for Patients With Recurrent Glioblastoma
Official Title  ICMJE A Phase I/II Multicenter Trial Evaluating the Association of Hypofractionated Stereotactic Radiation Therapy and the Anti-Programmed Death-ligand 1 (PD-L1) Durvalumab (Medi4736) for Patients With Recurrent Glioblastoma (STERIMGLI)
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 (local control rate) of the combined treatment in recurrent glioblastoma. In this Phase II part, patients will be assigned by randomization to one of the two following arms:

  • Arm A (control arm): Radiation therapy alone (17 patients)
  • Arm B (Experimental arm): Combined treatment with Anti-PD-L1 Durvalumab (33 patients)
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Glioblastoma
Intervention  ICMJE
  • Radiation: Hypofractionated stereotactic radiation therapy
  • Drug: Durvalumab
Study Arms  ICMJE
  • Active Comparator: Arm A: radiation therapy alone
    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.
    Intervention: Radiation: Hypofractionated stereotactic radiation therapy
  • Experimental: Arm B: combined treatment

    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.

    Interventions:
    • Radiation: Hypofractionated stereotactic radiation therapy
    • Drug: Durvalumab
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Suspended
Estimated Enrollment  ICMJE
 (submitted: August 10, 2016)
62
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE July 2020
Estimated Primary Completion Date April 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Age ≥ 18 years at time of study entry.
  2. Previous histopathologic confirmation of glioblastoma.
  3. Any line of recurrence of glioblastoma proven by contrast enhanced Magnetic Resonance Imaging (MRI) within 28 days prior to the first fraction of radiotherapy (RT), per modified Response Assessment in Neuro-Oncology (RANO) criteria.

    Note: Recurrence is defined as progression following therapy (i.e., chemotherapy, radiation, second surgery).

  4. 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.
  5. Recurrent disease documented by MRI evidence with a size of the recurrence evaluated on T1 post-gadolinium sequence ≤35mm.
  6. Patient for which a re-irradiation (by hFSRT) has been decided by the multidisciplinary medical board.
  7. Patients with measurable disease.
  8. 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).
  9. In case of previous anti-Vascular Endothelial Growth Factor (VEGF)/Vascular Endothelial Growth Factor Receptor (VEGFR) targeted therapy: at least 28 days between the last injection of anti-VEGF/VEGFR targeted therapy and the first fraction of RT.
  10. Karnofsky performance status ≥70.
  11. Adequate hematologic, renal and hepatic function, as defined below:

    • Absolute Neutrophil Count ≥ 1500/mm3
    • Haemoglobin ≥ 9.0 g/dL
    • Platelet count ≥ 100,000/mm3
    • Total bilirubin ≤ 1.5 x Upper Limit of Normal (ULN) (for patient with confirmed Gilbert's syndrome, Total bilirubin ≤ 3 x ULN)
    • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 x ULN
    • Creatinine ≤ 1.5 x ULN or creatinine clearance (CrCl) ≥ 40 mL/min, using the Cockcroft-Gault formula:

      • Female CrCl = (140 - age in years) x weight in kilograms (kg) x 0.85 /72 x serum creatinine in milligram/deciliter (mg/dL)
      • Male CrCl = (140 - age in years) x weight in kg x 1.00/72 x serum creatinine in mg/dL
  12. Female Patients must either be of non-reproductive potential (i.e., post-menopausal by history: ≥60 years old and no menses for ≥1 year without an alternative medical cause; or history of hysterectomy, or history of bilateral tubal ligation, or history of bilateral oophorectomy) or must have a negative serum pregnancy test upon study entry.
  13. Written informed consent and any locally required authorization (e.g., Social security for France (Health Insurance)) obtained from the patient prior performing any protocol-related procedures, including screening evaluations.
  14. Patient willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up.

Exclusion Criteria:

  1. Multifocal glioblastoma multiforme (GBM) recurrence.
  2. Distance between tumor and optic ways including chiasma or brainstem <1 cm.
  3. Prior re-irradiation.
  4. Prior exposure to Durvalumab or other anti-Programmed cell death 1(PD-1), anti-Programmed death-ligand 1(PD-L1), anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA4) antibodies.
  5. Patient who received a live vaccine within 30 days prior to the first fraction of RT.
  6. 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.
  7. Current or prior use of immunosuppressive medication within 28 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).
  8. Mean QT interval corrected for heart rate (QTc) ≥470 ms calculated from 3 electrocardiograms (ECGs) using Fridericia's Correction
  9. Presence of diffuse leptomeningeal disease or extracranial disease.
  10. Active suspected or prior documented autoimmune disease (including inflammatory bowel disease, celiac disease, irritable bowel syndrome, 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.

  11. Known primary immunodeficiency or active Human Immunodeficiency Virus (HIV).
  12. 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.
  13. History of organ transplant requiring use of immunosuppressive medication.
  14. History of active tuberculosis.
  15. Current pneumonitis or interstitial lung disease.
  16. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, active peptic ulcer disease or gastritis, active bleeding diatheses.
  17. Other invasive malignancy within 2 years prior to entry into the study, except for those treated with surgical therapy only.
  18. History of severe allergic reactions to any unknown allergens or any components of the study drug.
  19. Any prior Grade ≥ 3 immune-related adverse event (irAE) or any prior corticosteroid-refractory irAE.
  20. Participation in any other clinical trial involving another investigational product within 4 weeks prior to the first fraction of RT.
  21. Participation in any other clinical trial which delivered a dose >60 Gy for the primo-treatment for glioblastoma.
  22. Female patients who are pregnant, breast-feeding or male or female patients of reproductive potential who are not employing highly effective method of birth control.
  23. Any condition that, in the clinical judgment of the investigator, is likely to prevent the patient from complying with any aspect of the protocol or that may put the patient at unacceptable risk.
  24. Mental impairment (psychiatric illness/social situations) that may compromise the ability of the patient to give informed consent and comply with the requirements of the study.
  25. Patient who has forfeited his/her freedom by administrative or legal award or who is under guardianship.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE France
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02866747
Other Study ID Numbers  ICMJE 16TETE04
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Institut Claudius Regaud
Study Sponsor  ICMJE Institut Claudius Regaud
Collaborators  ICMJE AstraZeneca
Investigators  ICMJE Not Provided
PRS Account Institut Claudius Regaud
Verification Date August 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP