InformationClinical trials have complex eligibility criteria.
Always talk to your clinician about you’re interest in participating in a trial.
Learn why

Optimise reading forHealth ProfessionalsPatients

Recruitment on holdLast updated: 9 October 2023

PNOC019: This study is assessing the side effects of immunotherapy before and after surgery in treating children and young adults with high grade glioma that has come back (recurrent) or is increasing in scope or severity (progressive)A Randomized, Double-Blinded, Pilot Trial of Neoadjuvant Checkpoint Inhibition Followed by Combination Adjuvant Checkpoint Inhibition in Children and Young Adults With Recurrent or Progressive High Grade Glioma (HGG)

Clinical summary

Summary

Eligible participants will be randomly allocated to one of three treatment groups.

In Group A, participants will receive neoadjuvant immunotherapy (with nivolumab) intravenously (via IV) plus placebo via IV, 14 days before undergoing standard of care surgical resection. After recovery from surgery, participants will receive combination immunotherapy (with nivolumab + ipilimumab) on Day 1. Treatment repeats every 21 days for up to 3 cycles. After completion of combination infusion, participants will receive nivolumab via IV on Days 1 and 15. Cycles repeat every 28 days.

In Group B, participants will receive neoadjuvant combination immunotherapy (with nivolumab + ipilimumab) via IV, 14 days before undergoing standard of care surgical resection. After recovery from surgery, participants will receive combination immunotherapy (nivolumab + ipilimumab) via IV on Day 1. Treatment repeats every 21 days for up to 3 cycles. After completion of combination infusion, participants will receive nivolumab via IV on Days 1 and 15. Cycles repeat every 28 days.

In Group C, participants will receive neoadjuvant immunotherapy (with ipilimumab) via IV plus placebo via IV, 14 days before undergoing standard of care surgical resection. After recovery from surgery, participants will receive combination immunotherapy (with nivolumab + ipilimumab) via IV on Day 1. Treatment repeats every 21 days for up to 3 cycles. After completion of combination infusion, participants will receive nivolumab via IV over 30 minutes on DAys 1 and 15. Cycles repeat every 28 days. 

Cancer

Brain and Spinal Cancers Brain and Spinal

Age

People0 - 22

Phase

I

Trial Acronym

PNOC019

More information

Trial Identifiers

Use the hyperlinks, where available to access additional clinical trial information.

Trial sponsor

Sabine Mueller, MD, PhD

Scientific Title

A Randomized, Double-Blinded, Pilot Trial of Neoadjuvant Checkpoint Inhibition Followed by Combination Adjuvant Checkpoint Inhibition in Children and Young Adults With Recurrent or Progressive High Grade Glioma (HGG)

Eligibility

Inclusion

  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 < 22 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.
    • Participants must not have received prior exposure to CTLA4 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 and ipilimumab 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.

Exclusion

  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.

Inclusion

  • You have had treatment but your cancer has gotten worse or has not responded to the treatment you have been given.
  • You have had treatment, but your cancer has come back.

Exclusion

  • You have been diagnosed with a prior or secondary type of cancer.
  • You have certain types of non-cancer medical conditions.
  • You have had certain treatments, surgical procedures or drugs.
  • You have previously been treated (or are currently being treated) on a clinical trial.
Message

Clinical trials have complex eligibility criteria.

Ask your doctor if this trial could be right for you.

Participating hospitals

+ Show non-recruiting hospitals

On hold hospitals

InformationTell us if you find this trial availability is not accurate.Report inaccuracy

Get Support

Example

Cancer Connect

You might find it helpful to speak to someone who has 'been there before'. Our Cancer Connect program can provide one-on-one phone support from someone who understands what you're going through and has clinical trials experience.

Learn more

Example

Cancer Council’s cancer nurses

If you need cancer information and practical support for yourself, a carer, family or friend, contact Cancer Council’s experienced cancer nurses on 131120.

Learn more

Example

Information for family, friends and carers

When you are considering a cancer clinical trial, it is a good idea to discuss it with your family, friends or carers.

Learn more

Victorian Cancer Registry Victorian Government

The Victorian Cancer Trials Link is supported by the Victorian Government through the Victorian Cancer Agency.

RAP

Cancer Council Victoria would like to acknowledge the traditional custodians of the land on which we live and work. We would also like to pay respect to the elders past and present and extend that respect to all other Aboriginal people.