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Nivolumab in Combination With Temozolomide and Radiotherapy in Children and Adolescents With Newly Diagnosed High-grade Glioma (NIVOGLIO)

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ClinicalTrials.gov Identifier: NCT04267146
Recruitment Status : Recruiting
First Posted : February 12, 2020
Last Update Posted : February 12, 2020
Sponsor:
Information provided by (Responsible Party):
Gustave Roussy, Cancer Campus, Grand Paris

Brief Summary:

Multicenter, open label, prospective study including successively a phase I trial and then a phase II trial Phase I : Open label, non-randomized, safety run study in nine patients. In case of safety issue a -1 dose level will be tested.

Phase II : Open label, non randomized, efficacy study of nivolumab in addition to radiotherapy and temozolomide. This phase will start when the RP2D has been defined after the last patients evaluable for DLT achieved the first 6 weeks of treatment (the radio-chemotherapy period) with a DLT rate below 30% during the the phase I study.


Condition or disease Intervention/treatment Phase
High Grade Glioma Drug: Nivolumab Drug: Temozolomide Radiation: Radiotherapy Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description: Multicenter, open label, prospective study including successively a phase I trial and then a phase II trial
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase I-II Study of Nivolumab in Combination With Temozolomide and Radiotherapy in Children and Adolescents With Newly Diagnosed High-grade Glioma
Actual Study Start Date : July 15, 2019
Estimated Primary Completion Date : January 2023
Estimated Study Completion Date : January 2024

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: newly diagnosed high-grade glioma

Phase I : Open label, non-randomized, safety run study in nine patients. In case of safety issue a -1 dose level will be tested.

Phase II : Open label, non randomized, efficacy study of nivolumab in addition to radiotherapy and temozolomide. This phase will start when the RP2D has been defined after the last patients evaluable for DLT achieved the first 6 weeks of treatment (the radio-chemotherapy period) with a DLT rate below 30% during the the phase I study.

Drug: Nivolumab

Solution for intravenous injection 10 mg/ml. Initial dose : 3 mg/kg Nivolumab will be given at 3 mg/kg/injection every two weeks from the first day of radiotherapy to the last day of chemotherapy.

One de-escalation dose : 1 mg/kg


Drug: Temozolomide
Capsules: 5, 20, 100, 140, 180 and 250 mg orally. Temozolomide will be given at 75mg/m2/day from the day of start of radiotherapy to the last day of radiotherapy, then, after one month rest at 200mg/m2/day for five consecutive days for 12 cycles (28 days cycle).

Radiation: Radiotherapy
Total dose of 54 Gray(Gy) units delivered in 30 daily fractions of 1.8 Gy over 6 weeks during the chemoradiation period.




Primary Outcome Measures :
  1. Event Free Survival [ Time Frame: The clinical activity of the combined treatment will be evaluated by the 1-year event free survival (EFS) ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   3 Years to 18 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Written informed consent from parents/legal representative, patient, and age-appropriate assent before any study-specific screening procedures are conducted according to local, regional or national guidelines
  2. Age at inclusion: >/= 3 to <18 years of age
  3. Patients should be able and willing to comply with study visits and procedures as per protocol.
  4. Patients must be affiliated to a social security system or beneficiary of the same according to local requirements
  5. Sexually actice females of childbearing potential must have a negative serum pregnancy test within 24 hours prior to initiation of treatment. Sexually active women of childbearing potential must agree to use acceptable and appropriate contraception during the study and for at least 5 months after the last study treatment administration. Sexually active males patients (and their female partner) must agree to use condom during the study and for at least 7 months after the last study treatment administration.
  6. Newly diagnosed non-brainstem WHO grade III and IV HGG and neuroglial tumors; gliomatosis cerebri or diffuse glioma, metastatic malignant glial tumors, multifocal gliomas and bithalamic gliomas are eligible for the study. Diffuse midline gliomas with H3K27M mutation are not eligible. Anaplastic ganglioglioma and anaplastic pleïomorphic astrocytoma will be eligible.
  7. Local histological diagnosis after either stereotactic biopsy or surgical procedure has been confirmed centrally by a designated reference pathologist.
  8. Able to commence trial treatment within 6 weeks following the last major surgery.
  9. Adequate Bone Marrow Function : Hemoglobin >/= 10 g/dL (transfusion independent), Neutrophil count >/= 1.0 x 10^9/L.

    Platelet count >/= 1.0 x 10^9/L (transfusion independent)

  10. Absence of Coagulation Disorder
  11. Adequate Liver Function : AST </= 2.5x institutional ULN for age, ALT </= 2.5x institutional ULN for age, Total Bilirubin </= 1.5x institutional ULN for age
  12. Adequate Renal Function : Serum creatinine must be </= 1.5x ULN for age, absence of clinically significant proteinuria as defined by a screening early morning urine (first sample) dipstick urinalysis of </= 2

Exclusion Criteria:

  1. Any disease or condition that contraindicates the use of the study medication/treatment (for TMZ, see the approved product labelling) or places the patient at an unacceptable risk of experiencing treatment related complications.
  2. Patients should not be on high-dose steroids (ie > 1mg/kg) before study entry; doses should be stable for at least two weeks or decreasing.
  3. Low probability of protocol compliance.
  4. Radiological evidence of surgically related intracranial bleeding (excluding asymptomatic, resolving hemorrhagic changes associated with recent surgery and the presence of punctuate hemorrhage in the tumor).
  5. Subjects with concommitant second malignanices are excluded unless a complete remission is achieved as it is empirically determined based on the malignancy and treatment provided prior to study entry and no additional therapy is required or anticipated to be required during the study period.
  6. Previous cranial irradiation.
  7. Any known auto-immune disease, previous or ongoing.
  8. Known chronic inflammatory digestive disease, previous or ongoing.
  9. Chronic asthma receiving corticotherapy, even only with inhalation.
  10. Vaccinated with live attenuated vaccines within 4 weeks of the first dose of study drug
  11. Pregnant or breastfeeding women
  12. Known hypersensitivity to any component of the products (study drug or ingredients)
  13. Clinically significant, uncontrolled heart disease (including history of any cardiac arrhythmias, e.g., ventricular, supraventricular, nodal arrhythmias, or conduction abnormality within 12 months of screening).
  14. Patients who are currently receiving another investigational drug or anticancer agent
  15. Patient who have an uncontrolled infection
  16. Patient with known human immunodeficiency virus (HIV) / AIDS infection or acute / chronic Hepatitis B or C

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04267146


Contacts
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Contact: Jacques Grill, MD 0142114211 ext +33 jacques.grill@gustaveroussy.fr
Contact: Rachid Abbas 0142114211 ext +33 rachid.abbas@gustaveroussy.fr

Locations
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France
Gustave Roussy Recruiting
Villejuif, Val De Marne, France, 94800
Contact: Jacques Grill, MD    0142114211 ext +33    jacques.grill@gustaveroussy.fr   
Sponsors and Collaborators
Gustave Roussy, Cancer Campus, Grand Paris
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Responsible Party: Gustave Roussy, Cancer Campus, Grand Paris
ClinicalTrials.gov Identifier: NCT04267146    
Other Study ID Numbers: 2018-002688-24
2019/2797 ( Other Identifier: CSET number )
First Posted: February 12, 2020    Key Record Dates
Last Update Posted: February 12, 2020
Last Verified: February 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Nivolumab
Temozolomide
Antineoplastic Agents, Immunological
Antineoplastic Agents
Immune Checkpoint Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Alkylating
Alkylating Agents