ACTEMRA® for the Treatment of Pediatric Adamantinomatous Craniopharyngioma
ACTEMRA (tocilizumab) is an IL-6 receptor antagonist used for the treatment of adult Rheumatoid Arthritis as well as Polyarticular (PJIA) and Systemic (SJIA) Juvenile Idiopathic Arthritis. In this Phase II, the drug will be used to treat pediatric patients diagnosed with recurrent Adamantinomatous Craniopharyngioma including patients who have undergone surgery and/or radiation therapy.
Study details:
Adamantinomatous Craniopharyngioma (ACP) is a highly debilitating pediatric brain tumor that lacks medical anti-tumor therapies. Current therapy, which depends largely on surgery and radiation, is associated with poor quality of life and becomes more challenging and risky in the setting of recurrent disease. Recent discoveries regarding the biological characteristics of ACP indicate that available agents, including IL-6 pathway blockers may have efficacy in the control of ACP.
We hypothesize that the IL6- receptor antagonist ACTEMRA (tocilizumab) will be safe and effective at inducing tumor response in children with residual ACP. In this study, up to 38 patients will receive tocilizumab at the dose approved for pediatric Systemic Juvenile Idiopathic Arthritis (\< 30 kg: 12 mg/kg IV every 2 weeks; ≥30 kg: 8 mg/kg IV every 2 weeks). Therapy may continue for up to two years (26 cycles).
It will be a multi-center Phase 2 trial with two strata for patients aged \>1 year and \<25 years with unresectable ACP who may have been previously treated with radiation (Stratum 1, 18 patients) or without radiation (Stratum 2, 18 patients).
Eligibility criteria
Researchers look for people who fit a certain description, called eligibility criteria. See if you qualify.
Inclusion criteria
- Patients must be ≥ 12 months and ≤ 39 years of age at the time of study enrollment.
- Patients with histologically-confirmed adamantinomatous craniopharyngioma (ACP). Histologic confirmation of ACP may be made on solid tumor or, if no solid tumor can be safely obtained, cyst fluid with classic ACP characteristics of thick, cholesterol-rich, greenish-brown liquid in the context of imaging features consistent with craniopharyngioma, including lobulated, cystic/solid mass with calcifications that originates in the sellar/suprasellar region.
- Patients must have measurable disease.
- Stratum 1: Patients with progressive or recurrent ACP who demonstrate cystic and/or solid recurrence or progression at least 6 months post completion of radiation therapy.
- Stratum 2: Patients with measurable ACP who have undergone surgery but have NOT previously undergone irradiation (but may have received prior systemic or intracystic therapy). Progressive disease is allowed but not required.
- Karnofsky ≥ 50% for patients > 16 years of age and Lansky ≥ 50 for patients ≤ 16 years of age. Note: Neurologic deficits in patients with CNS tumors must have been stable for at least 7 days prior to study enrollment. Patients 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.
- Patients must have recovered or stabilized from the acute toxic effects of prior treatments.
- Adequate Bone Marrow Function: Peripheral absolute neutrophil count (ANC) ≥1000/mm3, Platelet count ≥100,000/mm3, Hemoglobin >8 g/dL.
- Adequate Renal Function: Creatinine clearance or radioisotope GFR > 70ml/min/1.73 m2 or maximum serum creatinine based on age/gender as specified.
- Adequate Liver Function: Total bilirubin within normal institutional limits, AST (SGOT) ≤ 2.5 × institutional upper limit of normal, ALT (SGPT) ≤ 2.5 × institutional upper limit of normal.
- Adequate Neurologic Function: Patients with neurological deficits should have deficits that are stable for a minimum of 1 week prior to enrollment. Patients with current seizure disorders may be enrolled if seizures are well-controlled on antiepileptic therapies.
- All patients and/or their parents or legally authorized representatives must sign a written informed consent.
Exclusion criteria
- Pregnant or breast-feeding women will not be entered on this study due to unknown risks of fetal and teratogenic adverse events.
- Patients with a history of serious gastrointestinal disease, including inflammatory bowel disease or gastrointestinal perforation.
- Patients receiving corticosteroids who have not been on a stable or decreasing dose of corticosteroid for at least 7 days prior to enrollment are not eligible.
- Patients who are currently receiving another investigational drug are not eligible.
- Patients who are currently receiving other anti-cancer agents are not eligible.
- Patients who have an uncontrolled infection are not eligible.
- Patients who have received any live or attenuated vaccinations within three months prior to start of therapy are not eligible.
- Any significant concurrent medical or surgical condition that would jeopardize the patient's safety or ability to complete the study.
- Patients who have a history of Human Immunodeficiency Virus, Hepatitis B Virus, Hepatitis C Virus or Tuberculosis infection are not eligible.
- Patients who have received a prior solid organ transplantation are not eligible.
- Patients who in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study are not eligible.
- Patients who have a history of alcohol, drug, or chemical abuse within 6 months of screening.
- Patients who have had major or intermediate surgery within the last 6 weeks or who have concerns for poor postsurgical wound healing.
- Patients who have a history of allergic reactions attributed to compounds of similar chemical or biologic composition to tocilizumab and its excipients are not eligible.
Eligibility
Age eligible for study : NA
Healthy volunteers accepted : No
Gender eligible for study: ALL
Things to know
Study dates
Study start:
Primary completion:
Study completion finish:
Study type
TREATMENT
Phase
- PHASE2
Study ID
NCT05233397
Intervention or treatment
DRUG: Tocilizumab
Conditions
- Adamantinomatous Craniopharyngioma
- Recurrent Adamantinomatous Craniopharyngioma
You may be eligible to participate in this trial based on your search. Check eligibility by answering some questions.
Research sites nearby
Closest Location:
Sydney Children's Hospital
Select from list below to view details:
Sydney Children's Hospital
Randwick, New South Wales, Australia
Queensland Children's Hospital
South Brisbane, Queensland, Australia
Perth Children's Hospital
Perth, Western Australia, Australia
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Who is running the clinical trial?
Nationwide Children's Hospital
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
| Participant Group/Arm | Intervention/Treatment |
|---|---|
EXPERIMENTAL: Stratum 1 and Stratum 2
| Drug: Tocilizumab |
What is the study measuring?
Primary Outcome
| Measure | Description | Time Frame |
|---|---|---|
| Sustained objective response rate of patients with recurrent/progressive previously irradiated ACP to treatment with systemic tocilizumab | To calculate the number of patients who experience sustained objective response rate \[minor response (MR) + partial response (PR) + complete response (CR)\] of patients with recurrent/progressive previously irradiated Adamantinomatous Craniopharyngioma to treatment with systemic tocilizumab (Stratum 1). | From Day 1 of treatment through 30 days following end of protocol treatment |
| Sustained objective response rate of patients with measurable ACP who have undergone surgery but have not been previously treated with radiation to treatment with systemic tocilizumab | To calculate the number of patients who experience sustained objective response rate (MR + PR + CR) of patients with measurable Adamantinomatous Craniopharyngioma who have undergone surgery but have not been previously treated with radiation to treatment with systemic tocilizumab (Stratum 2). | From Day 1 of treatment through 30 days following end of protocol treatment |
Secondary Outcome
| Measure | Description | Time Frame |
|---|---|---|
| Biological effects of tocilizumab on ACP tumor tissue and cyst fluid. | To measure the concentrations of IL-6, IL-8, IL-10, CXCL1, CXCR2, IDO-1 and IL-6R using a combination of ELISA, RNAseq, immunohistochemistry and immunofluorescence in cyst fluid or tumor tissue or blood. Comparisons will be made with known levels in the literature and among patient samples from within the study. | From Day 1 of treatment through 30 days following end of protocol treatment |
| Toxicities associated with tocilizumab in children with ACP | To calculate the number of participants with, as well as frequency and severity of, tocilizumab-related Adverse Events as assessed by CTCAE v5.0 in children with recurrent or refractory ACP. | From Day 1 of treatment through 30 days following end of protocol treatment |
| PFS of ACP patients treated with tocilizumab after radiation | To assess one-year progression-free survival (PFS) rates for patients with ACP who are treated with tocilizumab following progression after radiation (Stratum 1). | 12 months |
| PFS of ACP patients treated with tocilizumab who have not received radiation | To assess one-year progression-free survival (PFS) rates for patients with ACP who are treated with tocilizumab who have not previously received radiation (Stratum 2). | 12 months |
References
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