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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04323046


Additional trial details provided through ANZCTR are available at the end of this record.


Registration number
NCT04323046
Ethics application status
Date submitted
24/03/2020
Date registered
26/03/2020

Titles & IDs
Public title
Immunotherapy Before and After Surgery for Treatment of Recurrent or Progressive High Grade Glioma in Children and Young Adults
Scientific title
A Single Arm, Pilot of Neoadjuvant Checkpoint Inhibition Followed by Adjuvant Checkpoint Inhibition in Children and Young Adults With Recurrent or Progressive High Grade Glioma (HGG)
Secondary ID [1] 0 0
NCI-2020-01502
Secondary ID [2] 0 0
190815
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Glioblastoma 0 0
Malignant Glioma 0 0
Recurrent Glioblastoma 0 0
Recurrent Malignant Glioma 0 0
Recurrent Grade III Glioma 0 0
Grade III Glioma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Brain
Other 0 0 0 0
Research that is not of generic health relevance and not applicable to specific health categories listed above

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Other - Nivolumab
Other interventions - Quality-of-Life Assessment
Other interventions - Questionnaire Administration

Experimental: Neoadjuvant nivolumab and adjuvant nivolumab - NEOADJUVANT: Patients receive nivolumab IV over 30 minutes 14 days before undergoing standard of care surgical resection.

ADJUVANT MAINTENANCE: After completion of neoadjuvant infusion, patients receive nivolumab IV over 30 minutes on days 1 and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.


Treatment: Other: Nivolumab
Given IV

Other interventions: Quality-of-Life Assessment
Ancillary studies, given in person or online

Other interventions: Questionnaire Administration
Ancillary studies, given in person or online
Intervention code [1] 0 0
Treatment: Other
Intervention code [2] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Percentage change in cell cycle-related genetic signature
Timepoint [1] 0 0
From screening to surgery visit (neoadjuvant treatment groups); at time of recurrent high grade glioma (HGG) tissue collection (for archived non-treated samples)
Primary outcome [2] 0 0
Proportion of participants with treatment-related adverse events
Timepoint [2] 0 0
Up to 2 years
Secondary outcome [1] 0 0
Overall survival
Timepoint [1] 0 0
Up to 12 months
Secondary outcome [2] 0 0
Progression-free survival (PFS)
Timepoint [2] 0 0
Up to 12 months

Eligibility
Key inclusion criteria
1. Participants with recurrent or progressive high-grade gliomas (HGG) (World Health Organization (WHO) grade III or grade IV) who are candidates for surgical tumor debulking will be enrolled in this trial
2. All assessments are to occur within 14 days of registration except where otherwise noted. The participant and their legal parent/guardian must be thoroughly informed about all aspects of the study, including the study visit schedule and required evaluations and all regulatory requirements for informed consent. The written informed consent must be obtained from the participant and legal parent/guardian prior to enrollment
3. Have a history of previously treated histologically confirmed World Health Organization grade III or IV HGG. Previous first line therapy with radiation and/or chemotherapy
4. Have evidence of recurrence or progression of disease by MRI scan
5. Participants must be adequate medical candidates for surgical resection. The intent of surgical resection is to allow both cytoreduction and tumor debulking as part of standard of care, and also collect a minimum of 100 mg of tumor tissue for the study tissue endpoints
6. A primary goal of surgery must be cytoreduction, and not solely on diagnostic biopsy
7. Age: Participants must be > 6 months and < 25 years of age at time of enrollment
8. Karnofsky >= 50 for participants > 16 years of age and Lansky >= 50 for participants =< 16 years of age. Participants who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score
9. Patients with neurological deficits should have deficits that are stable for a minimum of 1 week prior to enrollment (on stable or tapering dosing of steroids). A baseline detailed neurological exam should clearly document the neurologic status of the patient at the time of enrollment on the study.
10. Prior Therapy: Participants must have fully recovered from the acute toxic effects of all prior anti-cancer therapy and must meet the following minimum duration from prior anti-cancer directed therapy prior to enrollment. If after the required timeframe, the defined eligibility criteria are met, e.g. blood count criteria, the patient is considered to have recovered adequately

* Cytotoxic chemotherapy or other anti-cancer agents known to be myelosuppressive. At least 21 days after the last dose of cytotoxic or myelosuppressive chemotherapy (42 days if prior nitrosourea)
* An interval of at least 12 weeks from the completion of radiation therapy to registration unless there is unequivocal histologic confirmation of tumor progression
* Hematopoietic growth factors: At least 14 days after the last dose of a long-acting growth factor (e.g. pegfilgrastim) or 7 days for short acting growth factor. For agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events (AEs) are known to occur. The duration of this interval must be discussed with the study chair.

* Had their last dose of biologic (anti-neoplastic agent) =7 days prior to study registration, or beyond the time during which AEs are known to occur.
* Anti-cancer agents not known to be myelosuppressive (e.g. not associated with reduced platelet or absolute neutrophil count [ANC] counts): At least 7 days after the last dose of agent
* Interleukins, interferons and cytokines (other than hematopoietic growth factors): >= 21 days after the completion of interleukins, interferon or cytokines (other than hematopoietic growth factors)
* Antibodies: >= 21 days must have elapsed from infusion of last dose of antibody, and toxicity related to prior antibody therapy must be recovered to grade =< 1
* An interval of at least 12 weeks from prior exposure to PD-1 or PD-L1 inhibitors.
* Stem cell infusion (with or without total-body irradiation (TBI)):

* Autologous stem cell infusion including boost infusion: >= 42 days
11. Participants must be willing to forego cytotoxic anti-tumor therapies except study-defined therapy while being treated on study
12. Organ Function Requirements:

* Peripheral absolute neutrophil count (ANC) >= 1000/mm^3
* Platelet count >= 100,000/mm^3
* Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 mL/min/1.73 m^2 OR a serum creatinine based on age/gender as follows:

* Age: Maximum Serum Creatinine (mg/dL)
* 6 months to < 3 years: 0.6 (male and female)
* 3 to < 6 years: 0.8 (male and female)
* 6 to < 10 years: 1 (male and female)
* 10 to < 13 years: 1.2 (male and female)
* 13 to < 16 years: 1.5 (male), 1.4 (female)
* >= 16 years: 1.7 (male), 1.4 (female)
* Bilirubin (sum of conjugated and unconjugated) =< 1.5 x upper limit of normal (ULN) for age (except participants with Gilbert syndrome who must have a total bilirubin level of < 3.0
* Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 3.0 x ULN
* Serum albumin >= 2
13. Pregnancy: The effects of nivolumab on the developing human fetus are unknown. For this reason women of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation and 5 months after completion of therapy. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately.
14. MRI within 28 days prior to registration.
Minimum age
6 Months
Maximum age
25 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Current or planned participation in a study of an investigational agent or using an investigational device.
2. Has a diagnosis of immunodeficiency.
3. Has tumor primarily localized to the brainstem or spinal cord.
4. Has presence of diffuse leptomeningeal disease or or disseminated/multi-focal disease, or extracranial disease.
5. Has received systemic immunosuppressive treatments (such as methotrexate, chloroquine, azathioprine, etc.), aside from anti-neoplastic chemotherapy or systemic corticosteroids within six months of registration.
6. Participants with a concurrent condition requiring systemic treatment with either corticosteroids (> 0.25 mg/kg daily prednisone equivalent) or other immunosuppressive medications within 14 days of start of study treatment. Inhaled or topical steroids, and adrenal replacement steroid doses > 0.25 mg/kg daily prednisone equivalent, are permitted in the absence of active autoimmune disease.
7. Unable to taper steroids due to ongoing mass effect; a maximum dexamethasone dose of 0.1 mg/kg/day is allowed (4mg maximum), but preferably have been discontinued (inhaled or topical use of steroids is allowed).
8. Has a known history of active TB (Bacillus tuberculosis).
9. Has a known additional malignancy that is progressing or requires active treatment within 3 years of registration. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy.
10. Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g. thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
11. Has known history of, or any evidence of active non-infectious pneumonitis.
12. Has an active infection requiring systemic therapy.
13. Has a known hypersensitivity to any of the study therapy products.
14. Has a known history of positive test for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS).

* NOTE: Testing for HIV must be performed at sites where mandated locally
15. Any prior positive test result for hepatitis B virus or hepatitis C virus indicating presence of virus, e.g., hepatitis B surface antigen (HBsAg, Australia antigen) positive, or hepatitis C antibody (anti-HCV) positive (except if HCV-ribonucleic acid (RNA) negative).
16. Participants who have had prior allogenic hematopoietic stem cell transplant (HSCT).
17. Any serious or uncontrolled medical disorder that, in the opinion of the investigator may increase the risk associated with study participation or study drug administration, impair the ability of the participant to receive protocol therapy or interfere with interpretation of study results.

Study design
Purpose of the study
Treatment
Allocation to intervention
NA
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
2/10/2020
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/03/2029
Actual
Sample size
Target
20
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,VIC,WA
Recruitment hospital [1] 0 0
Sydney Children's Hospital - Sydney
Recruitment hospital [2] 0 0
The Children's Hospital at Westmead - Westmead
Recruitment hospital [3] 0 0
Queensland Children's Hospital - South Brisbane
Recruitment hospital [4] 0 0
Women's and Children's Hospital - North Adelaide
Recruitment hospital [5] 0 0
Royal Children's Hospital - Parkville
Recruitment hospital [6] 0 0
Perth Children's' Hospital - Perth
Recruitment postcode(s) [1] 0 0
1291 - Sydney
Recruitment postcode(s) [2] 0 0
2152 - Westmead
Recruitment postcode(s) [3] 0 0
4101 - South Brisbane
Recruitment postcode(s) [4] 0 0
5006 - North Adelaide
Recruitment postcode(s) [5] 0 0
3052 - Parkville
Recruitment postcode(s) [6] 0 0
6009 - Perth
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
District of Columbia
Country [4] 0 0
United States of America
State/province [4] 0 0
Florida
Country [5] 0 0
United States of America
State/province [5] 0 0
Indiana
Country [6] 0 0
United States of America
State/province [6] 0 0
Maryland
Country [7] 0 0
United States of America
State/province [7] 0 0
Massachusetts
Country [8] 0 0
United States of America
State/province [8] 0 0
Missouri
Country [9] 0 0
United States of America
State/province [9] 0 0
New Jersey
Country [10] 0 0
United States of America
State/province [10] 0 0
Oregon
Country [11] 0 0
United States of America
State/province [11] 0 0
Utah
Country [12] 0 0
Israel
State/province [12] 0 0
Ramat Gan
Country [13] 0 0
Switzerland
State/province [13] 0 0
Zurich

Funding & Sponsors
Primary sponsor type
Other
Name
Sabine Mueller, MD, PhD
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
Pacific Pediatric Neuro-Oncology Consortium
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Tom Davidson ([email protected]), MD
Address 0 0
Children's Hospital Los Angeles
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Jannerfer An
Address 0 0
Country 0 0
Phone 0 0
(415) 476-3831
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT04323046

Additional trial details provided through ANZCTR
Accrual to date
Recruiting in Australia
Recruitment state(s)
ACT,NSW,NT,QLD,SA,WA,VIC
Recruitment hospital [1] 24
The Children's Hospital at Westmead
Recruitment hospital [2] 25
Monash Children’s Hospital
Recruitment hospital [3] 26
Perth Children's Hospital
Recruitment hospital [4] 27
Queensland Children's Hospital
Recruitment hospital [5] 28
The Royal Childrens Hospital
Recruitment hospital [6] 29
Sydney Children's Hospital
Recruitment hospital [7] 30
Womens and Childrens Hospital
Recruitment postcode(s) [1] 29
2145
Recruitment postcode(s) [2] 30
3168
Recruitment postcode(s) [3] 31
6009
Recruitment postcode(s) [4] 32
4101
Recruitment postcode(s) [5] 33
3052
Recruitment postcode(s) [6] 34
2031
Recruitment postcode(s) [7] 35
5006
Funding & Sponsors
Primary sponsor
Other Collaborative groups
Primary sponsor name
Australia and New Zealand Children’s Haematology/Oncology Group (ANZCHOG)
Primary sponsor address
27-31 Wright Street, Clayton, VIC, 3168
Primary sponsor country
Australia
Ethics approval
Ethics application status
Approved
Ethics committee name [1] 27
The Royal Children's Hospital Health Research Ethics Committee
Address [1] 27
50 Flemington Road, Parkville, VIC 3052
Country [1] 27
Australia
Date submitted for ethics approval [1] 27
03/07/2020
Approval date [1] 27
06/11/2020
Ethics approval number [1] 27
65822
 
Public notes
New Zealand sites:
Starship Children's Hospital

Contacts
Principal investigator
Title 253 0
Prof
Name 253 0
Nick Gottardo
Address 253 0
Oncology and Haematology, 15 Hospital Avenue, Nedlands WA 6009
Country 253 0
Australia
Phone 253 0
+618 6456 0241
Fax 253 0
Email 253 0
[email protected]
Contact person for public queries
Title 254 0
Mrs
Name 254 0
Robyn Strong
Address 254 0
27-31 Wright Street, Clayton, VIC, 3168
Country 254 0
Australia
Phone 254 0
+613 8572 2684
Fax 254 0
+613 9902 4810
Email 254 0
[email protected]
Contact person for scientific queries
Title 255 0
Prof
Name 255 0
Nick Gottardo
Address 255 0
Oncology and Haematology, 15 Hospital Avenue, Nedlands WA 6009
Country 255 0
Australia
Phone 255 0
+618 6456 0241
Fax 255 0
Email 255 0
[email protected]