Adamantinomatous CraniopharyngiomaPhase 2NCT05233397
ACTEMRA® for the Treatment of Pediatric Adamantinomatous Craniopharyngioma
A Phase 2 study testing Tocilizumab in people with Adamantinomatous Craniopharyngioma and Recurrent Adamantinomatous Craniopharyngioma, run by Nationwide Children's Hospital at 14 sites in 3 countries.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 1 year to 39 years
- Conditions the study is for
- Adamantinomatous Craniopharyngioma, Recurrent Adamantinomatous Craniopharyngioma
- What is being tested?
- Tocilizumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 14 sitesin 3 countries
- Study dates
- 16 Dec 2022to Dec 2029
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 1 year to 39 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Age: Patients must be ≥ 12 months and ≤ 39 years of age at the time of study enrollment.
- Diagnosis: 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.
- Disease Status: 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 (CLOSED): 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.
- Performance Level: Karnofsky ≥ 50% for patients > 16 years of age and Lansky ≥ 50 for patients ≤ 16 years of age (See Appendix I). 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.
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- Prior Therapy: Patients must have recovered or stabilized from the acute toxic effects of prior treatments
- Biologic (anti-neoplastic agent): At least 7 days must have elapsed after the last (systemic or intracystic) dose of a biologic agent. 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 are known to occur. The duration of this interval must be discussed with the study chair
- Immunotherapy: At least 42 days after the completion of any type of systemic immunotherapy, e.g. tumor vaccines.
- Monoclonal antibodies: At least 21 days after the last dose of a monoclonal antibody.
- Radiation therapy: Patients must have had their last (conventional or hypofractionated) fraction of: a) Focal irradiation > 6 months prior to enrollment and b) No prior craniospinal irradiation is permitted.
- Corticosteroids: Patients receiving dexamethasone must be on a stable or decreasing dose for at least 1 week prior to enrollment
- Myelosuppressive systemic therapy: At least 21 days must have elapsed after the last systemic myelosuppressive therapy.
- Surgery: At least 6 weeks must have elapsed since major or intermediate surgery. Major surgery includes major craniotomy for tumor resection or cyst fenestration, organ resection, exploratory laparotomy. Intermediate procedures include ventriculoperitoneal shunt placement, stereotactic brain biopsy and intraventricular catheter placement. Minor procedures that are not excluded include skin biopsy/incision and drainage, bone marrow aspirate, and central venous catheter placement. Ommaya aspirations and Lumbar Punctures are considered minor procedures..
- Organ Function Requirements
- Adequate Bone Marrow Function Defined as:
- Peripheral absolute neutrophil count (ANC) ≥1000/mm3
- Platelet count ≥100,000/mm3 (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment)
- Hemoglobin >8 g/dL (may be transfused)
- Adequate Renal Function Defined as:
- Creatinine clearance or radioisotope GFR > 70ml/min/1.73 m2 or
- A serum creatinine based on (Schwartz et al. J. Peds, 106:522, 1985) age/gender as follows:
- 1 to < 2 years: maximum serum creatinine 0.6 mg/dL for males and females. 2 to < 6 years: maximum serum creatinine 0.8 mg/dL for males and females. 6 to < 10 years: maximum serum creatinine 1.0 mg/dL for males and females. 10 to < 13 years: maximum serum creatinine 1.2 mg/dL for males and females. 13 to < 16 years: maximum serum creatinine 1.5 mg/dL for males and 1.4 mg/dL for females.
- ≥ 16 years: maximum serum creatinine 1.7 mg/dL for males and 1.4 mg/dL for females.
- Adequate Liver Function Defined as:
- 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 Defined as:
- 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.
- Informed Consent: All patients and/or their parents or legally authorized representatives must sign a written informed consent. Assent, when appropriate, will be obtained according to institutional guidelines.
Who cannot join
- Pregnancy or Breast-Feeding: Pregnant or breast-feeding women will not be entered on this study due to unknown risks of fetal and teratogenic adverse events as seen in animal/human studies. Pregnancy tests must be obtained in girls who are post-menarchal. Males or females of reproductive potential may not participate unless they have agreed to use an effective contraceptive method for at least 90 days after discontinuation of drug for females and at least 60 days for males. For females of childbearing potential, agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods (bilateral tubal ligation, male sterilization, hormonal contraceptives that inhibit ovulation, hormone-releasing intrauterine devices, and copper intrauterine devices; hormonal contraceptive methods must be supplemented by a barrier method) and agreement to refrain from donating eggs are required. For males of reproductive potential, agreement to remain abstinent (refrain from heterosexual intercourse) or use a condom, and agreement to refrain from donating sperm.
- Gastrointestinal Disease: Patients with a history of serious gastrointestinal disease, including inflammatory bowel disease or gastrointestinal perforation
- Concomitant Medications
- Corticosteroids: 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.
- Investigational Drugs: Patients who are currently receiving another investigational drug are not eligible.
- Anti-cancer Agents: Patients who are currently receiving other anti-cancer agents are not eligible.
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- Study Specific:
- 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, including, but not limited to, disease of the nervous, renal, hepatic, cardiac (such as symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia), pulmonary, or endocrine system
- 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.
Trial locations and contacts
14 sites in 3 countries. Contact the study team or a site near you to ask about taking part.
14 sites in 3 countries
United States8 sites, 7 recruiting
- Recruiting
Children's Hospital Colorado
Aurora, Colorado, 80045
Holly Lindsay, MD, 720-777-6740, Holly.Lindsay@childrenscolorado.org
- Recruiting
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229
Peter de Blank, MD, 513-517-2068, Peter.deBlank@cchmc.org
- Recruiting
Nationwide Children's Hospital
Columbus, Ohio, 43235
Maryam Fouladi, MD, 614-722-5758, Maryam.fouladi@nationwidechildrens.org
- Recruiting
Duke Children's Hospital
Durham, North Carolina, 27710
Daniel Landi, MD, 919-668-6688
- Recruiting
Texas Children's Hospital
Houston, Texas, 77030
Patricia Baxter, MD, 8328244681, pabaxter@txch.org
- Active, not recruiting
Nicklaus Children's Hospital
Miami, Florida, 33155
- Recruiting
Seattle Children's Hospital
Seattle, Washington, 98105
Rebecca Ronsley, MD, FRCPC, 206-987-2106, Rebecca.Ronsley@seattlechildrens.org
- Recruiting
Children's National Medical Center
Washington D.C., District of Columbia, 20010
Eugene Hwang, MD, 202-476-5046, ehwang@childrensnational.org
Australia3 sites, 3 recruiting
- Recruiting
Perth Children's Hospital
Perth, Western Australia, 6000
Santosh Valvi, MBChB, 61 8 6456 0241, santosh.valvi@health.wa.gov.au
- Recruiting
Sydney Children's Hospital
Randwick, New South Wales, 2031
Neevika Manoharan, MBBS, 61 2 9382 1730, Neevika.Manoharan@health.nsw.gov.au
- Recruiting
Queensland Children's Hospital
South Brisbane, Queensland, 4101
Tim Hassall, MBBS, 61 7 3068 3593, tim.hassall@health.qld.gov.au
Canada3 sites, 3 recruiting
- Recruiting
Stollery Children's Hospital
Edmonton, Alberta, T6G2B7
Liana Nobre, liana.nobre@albertahealthservices.ca
- Recruiting
McGill University Health Center
Montreal, Quebec
Genevieve Legault, MD, genevieve.legault4@mcgill.caca
- Recruiting
The Hospital for Sick Children (SickKids)
Toronto, Ontario, M5G1X8
Julie Bennett, MD, julie.bennett@sickkids.ca
About this study
Official title: Phase 2 Study of Systemic IL-6 Receptor Antagonist ACTEMRA® (Tocilizumab) for the Treatment of Progressive/Recurrent 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.
Read the detailed description
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-CLOSED to enrollment).
- Being tested
- Tocilizumab
- Medical subject headings
- Craniopharyngioma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TocilizumabDrug
Also called ACTEMRA®
For < 30 kg: 12 mg/kg IV every 2 weeks; For ≥30 kg: 8 mg/kg IV every 2 weeks
| Study group | Role | What they receive |
|---|---|---|
| Stratum 1 and Stratum 2 | Experimental | Stratum 1: Patients with progressive or recurrent adamantinomatous craniopharyngiomas following radiation therapy.
Stratum 2 (CLOSED): Patients with measurable adamantinomatous craniopharyngioma who have undergone surgery but have not previously received radiation therapy. Progressive disease is allowed but not required Receives: Drug: Tocilizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: 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).
Measured: From Day 1 of treatment through 30 days following end of protocol treatment
Secondary outcomes (4)
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.
Measured: 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.
Measured: 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).
Measured: 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).
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Feb 2022
- Study start16 Dec 2022
- Primary completionDec 2027 (estimated)
- Study completionDec 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (16)Papers the sponsor has linked to this study.
- Other trials for Adamantinomatous CraniopharyngiomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- ACTEMRA® (tocilizumab)
- Masking
- None (open label)
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Nationwide Children's Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Children's Hospital Colorado
- Responsible party
- Sponsor
- Investigators
- Holly Lindsay, MD, Study chair, Children's Hospital ColoradoTodd C Hankinson, MD, Study chair, Children's Hospital ColoradoMaryam Fouladi, MD, Principal investigator, Nationwide Children's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05233397
- Sponsor's protocol ID
- CONNECT1905
- Status last verified
- Mar 2026
- First submitted
- 25 Jan 2022
- Last updated
- 23 Apr 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Brunner HI, Ruperto N, Zuber Z, Keane C, Harari O, Kenwright A, Lu P, Cuttica R, Keltsev V, Xavier RM, Calvo I, Nikishina I, Rubio-Perez N, Alexeeva E, Chasnyk V, Horneff G, Opoka-Winiarska V, Quartier P, Silva CA, Silverman E, Spindler A, Baildam E, Gamir ML, Martin A, Rietschel C, Siri D, Smolewska E, Lovell D, Martini A, De Benedetti F; Paediatric Rheumatology International Trials Organisation PRINTO; Pediatric Rheumatology Collaborative Study Group (PRCSG). Efficacy and safety of tocilizumab in patients with polyarticular-course juvenile idiopathic arthritis: results from a phase 3, randomised, double-blind withdrawal trial. Ann Rheum Dis. 2015 Jun;74(6):1110-7. doi: 10.1136/annrheumdis-2014-205351. Epub 2014 May 16.
PubMed 24834925Roszkiewicz J, Orczyk K, Smolewska E. Tocilizumab in the treatment of systemic-onset juvenile idiopathic arthritis - single-centre experience. Reumatologia. 2018;56(5):279-284. doi: 10.5114/reum.2018.79497. Epub 2018 Oct 31.
PubMed 30505008Choy EH, Isenberg DA, Garrood T, Farrow S, Ioannou Y, Bird H, Cheung N, Williams B, Hazleman B, Price R, Yoshizaki K, Nishimoto N, Kishimoto T, Panayi GS. Therapeutic benefit of blocking interleukin-6 activity with an anti-interleukin-6 receptor monoclonal antibody in rheumatoid arthritis: a randomized, double-blind, placebo-controlled, dose-escalation trial. Arthritis Rheum. 2002 Dec;46(12):3143-50. doi: 10.1002/art.10623.
PubMed 12483717De Benedetti F, Brunner HI, Ruperto N, Kenwright A, Wright S, Calvo I, Cuttica R, Ravelli A, Schneider R, Woo P, Wouters C, Xavier R, Zemel L, Baildam E, Burgos-Vargas R, Dolezalova P, Garay SM, Merino R, Joos R, Grom A, Wulffraat N, Zuber Z, Zulian F, Lovell D, Martini A; PRINTO; PRCSG. Randomized trial of tocilizumab in systemic juvenile idiopathic arthritis. N Engl J Med. 2012 Dec 20;367(25):2385-95. doi: 10.1056/NEJMoa1112802.
PubMed 23252525Donson AM, Apps J, Griesinger AM, Amani V, Witt DA, Anderson RCE, Niazi TN, Grant G, Souweidane M, Johnston JM, Jackson EM, Kleinschmidt-DeMasters BK, Handler MH, Tan AC, Gore L, Virasami A, Gonzalez-Meljem JM, Jacques TS, Martinez-Barbera JP, Foreman NK, Hankinson TC; Advancing Treatment for Pediatric Craniopharyngioma Consortium. Molecular Analyses Reveal Inflammatory Mediators in the Solid Component and Cyst Fluid of Human Adamantinomatous Craniopharyngioma. J Neuropathol Exp Neurol. 2017 Sep 1;76(9):779-788. doi: 10.1093/jnen/nlx061.
PubMed 28859336Grob S, Mirsky DM, Donson AM, Dahl N, Foreman NK, Hoffman LM, Hankinson TC, Mulcahy Levy JM. Targeting IL-6 Is a Potential Treatment for Primary Cystic Craniopharyngioma. Front Oncol. 2019 Aug 21;9:791. doi: 10.3389/fonc.2019.00791. eCollection 2019.
PubMed 31497533Gump JM, Donson AM, Birks DK, Amani VM, Rao KK, Griesinger AM, Kleinschmidt-DeMasters BK, Johnston JM, Anderson RC, Rosenfeld A, Handler M, Gore L, Foreman N, Hankinson TC. Identification of targets for rational pharmacological therapy in childhood craniopharyngioma. Acta Neuropathol Commun. 2015 May 21;3:30. doi: 10.1186/s40478-015-0211-5.
PubMed 25990246Gust J, Hay KA, Hanafi LA, Li D, Myerson D, Gonzalez-Cuyar LF, Yeung C, Liles WC, Wurfel M, Lopez JA, Chen J, Chung D, Harju-Baker S, Ozpolat T, Fink KR, Riddell SR, Maloney DG, Turtle CJ. Endothelial Activation and Blood-Brain Barrier Disruption in Neurotoxicity after Adoptive Immunotherapy with CD19 CAR-T Cells. Cancer Discov. 2017 Dec;7(12):1404-1419. doi: 10.1158/2159-8290.CD-17-0698. Epub 2017 Oct 12.
PubMed 29025771Mihara M, Kasutani K, Okazaki M, Nakamura A, Kawai S, Sugimoto M, Matsumoto Y, Ohsugi Y. Tocilizumab inhibits signal transduction mediated by both mIL-6R and sIL-6R, but not by the receptors of other members of IL-6 cytokine family. Int Immunopharmacol. 2005 Nov;5(12):1731-40. doi: 10.1016/j.intimp.2005.05.010.
PubMed 16102523Nellan A, McCully CML, Cruz Garcia R, Jayaprakash N, Widemann BC, Lee DW, Warren KE. Improved CNS exposure to tocilizumab after cerebrospinal fluid compared to intravenous administration in rhesus macaques. Blood. 2018 Aug 9;132(6):662-666. doi: 10.1182/blood-2018-05-846428. Epub 2018 Jun 28. No abstract available.
PubMed 29954750Nishimoto N, Kishimoto T. Inhibition of IL-6 for the treatment of inflammatory diseases. Curr Opin Pharmacol. 2004 Aug;4(4):386-91. doi: 10.1016/j.coph.2004.03.005.
PubMed 15251133Nishimoto N, Kishimoto T. Humanized antihuman IL-6 receptor antibody, tocilizumab. Handb Exp Pharmacol. 2008;(181):151-60. doi: 10.1007/978-3-540-73259-4_7.
PubMed 18071945Nishimoto N, Yoshizaki K, Maeda K, Kuritani T, Deguchi H, Sato B, Imai N, Suemura M, Kakehi T, Takagi N, Kishimoto T. Toxicity, pharmacokinetics, and dose-finding study of repetitive treatment with the humanized anti-interleukin 6 receptor antibody MRA in rheumatoid arthritis. Phase I/II clinical study. J Rheumatol. 2003 Jul;30(7):1426-35.
PubMed 12858437Nishimoto N, Yoshizaki K, Miyasaka N, Yamamoto K, Kawai S, Takeuchi T, Hashimoto J, Azuma J, Kishimoto T. Treatment of rheumatoid arthritis with humanized anti-interleukin-6 receptor antibody: a multicenter, double-blind, placebo-controlled trial. Arthritis Rheum. 2004 Jun;50(6):1761-9. doi: 10.1002/art.20303.
PubMed 15188351Sato K, Tsuchiya M, Saldanha J, Koishihara Y, Ohsugi Y, Kishimoto T, Bendig MM. Reshaping a human antibody to inhibit the interleukin 6-dependent tumor cell growth. Cancer Res. 1993 Feb 15;53(4):851-6.
PubMed 8428365