ACTEMRA® for the Treatment of Pediatric Adamantinomatous Craniopharyngioma
Rekrutierend
NCT-Nummer:
NCT05233397
Studienbeginn:
Dezember 2022
Letztes Update:
08.08.2024
Wirkstoff:
Tocilizumab
Indikation (Clinical Trials):
Craniopharyngioma, Adamantinoma
Geschlecht:
Alle
Altersgruppe:
Alle
Phase:
Phase 2
Sponsor:
Nationwide Children's Hospital
Collaborator:
Children's Hospital Colorado
Studienleiter
Kathleen H Dorris, MD Study ChairChildren's Hospital Colorado
Todd C Hankinson, MD Study ChairChildren's Hospital Colorado
Maryam Fouladi, MD Principal InvestigatorNationwide Children's Hospital
Kontakt
Amy K Jones, MSN Kontakt: Phone: 16147223284 E-Mail: Amy.Jones1@nationwidechildrens.org» Kontaktdaten anzeigen
Studienlocations (3 von 17)
Aurora United States Washington Chicago Boston Durham Cincinnati Columbus Houston Seattle Randwick Australia South Brisbane Perth Toronto Canada Montréal Heidelberg Baden-Württemberg Germany Utrecht Netherlands London United Kingdom
Hopp Children's Cancer Center at NCT Heidelberg (KiTZ) 69120 Heidelberg (Baden-Württemberg) GermanyNoch nicht rekrutierend » Google-Maps Ansprechpartner: Olaf Witt, MD Phone: 49 6221 42 3570 E-Mail: o.witt@kitz-heidelberg.de» Ansprechpartner anzeigen Children's Hospital Colorado 80045 Aurora United StatesNoch nicht rekrutierend » Google-Maps Ansprechpartner: Kathleen Dorris, MD Phone: 720-777-8314 E-Mail: kathleen.dorris@childrenscolorado.org» Ansprechpartner anzeigen Children's National Medical Center 20010 Washington United StatesNoch nicht rekrutierend » Google-Maps Ansprechpartner: Eugene Hwang, MD Phone: 202-476-5046 E-Mail: ehwang@childrensnational.org» Ansprechpartner anzeigen Ann & Robert H. Lurie Children's Hospital of Chicago 60611 Chicago United StatesNoch nicht rekrutierend » Google-Maps Ansprechpartner: Ashley Plant, MD Phone: 312-227-4090 E-Mail: Aplant@luriechildrens.org» Ansprechpartner anzeigen Dana-Farber Cancer Institute 02215 Boston United StatesNoch nicht rekrutierend » Google-Maps Ansprechpartner: Susan Chi, MD Phone: 617-632-4386 E-Mail: Susan_chi@dfci.harvard.edu» Ansprechpartner anzeigen Duke University Health System 27708 Durham United StatesNoch nicht rekrutierend » Google-Maps Ansprechpartner: David H Ashley Phone: 919-681-3824 E-Mail: david.ashley@duke.edu» Ansprechpartner anzeigen Cincinnati Children's Hospital Medical Center 45229 Cincinnati United StatesRekrutierend » Google-Maps Ansprechpartner: Peter de Blank, MD Phone: 513-517-2068 E-Mail: Peter.deBlank@cchmc.org» Ansprechpartner anzeigen Nationwide Children's Hospital 43235 Columbus United StatesRekrutierend » Google-Maps Ansprechpartner: Maryam Fouladi, MD Phone: 614-722-5758 E-Mail: Maryam.fouladi@nationwidechildrens.org» Ansprechpartner anzeigen Texas Children's Hospital 77030 Houston United StatesNoch nicht rekrutierend » Google-Maps Ansprechpartner: Patricia Baxter, MD Phone: 832-824-4681 E-Mail: pabaxter@txch.org» Ansprechpartner anzeigen Seattle Children's Hospital 98105 Seattle United StatesRekrutierend » Google-Maps Ansprechpartner: Rebecca Ronsley, MD Phone: 206-987-2106 E-Mail: rebecca.ronsley@seattlechildrens.org» Ansprechpartner anzeigen Sydney Children's Hospital 2031 Randwick AustraliaRekrutierend » Google-Maps Ansprechpartner: Neevika Manoharan, MBBS Phone: 61 2 9382 1730 E-Mail: Neevika.Manoharan@health.nsw.gov.au» Ansprechpartner anzeigen Queensland Children's Hospital 4101 South Brisbane AustraliaNoch nicht rekrutierend » Google-Maps Ansprechpartner: Tim Hassall, MBBS Phone: 61 7 3068 3593 E-Mail: tim.hassall@health.qld.gov.au» Ansprechpartner anzeigen Perth Children's Hospital 6000 Perth AustraliaRekrutierend » Google-Maps Ansprechpartner: Santosh Valvi, MBChB Phone: 61 8 6456 0241 E-Mail: santosh.valvi@health.wa.gov.au» Ansprechpartner anzeigen The Hospital for Sick Children (SickKids) M5G1X8 Toronto CanadaNoch nicht rekrutierend » Google-Maps Ansprechpartner: Eric Bouffet, MD Phone: 416-813-7457 E-Mail: eric.bouffet@sickkids.ca» Ansprechpartner anzeigen Montreal Children's Hospital H4A3J1 Montréal CanadaNoch nicht rekrutierend » Google-Maps Ansprechpartner: Genevieve Legault, MD Phone: 514-412-4400 Phone (ext.): 60497 E-Mail: Genevieve.legault4@mcgill.ca» Ansprechpartner anzeigen Jasper van der Lugt 3720 Utrecht NetherlandsNoch nicht rekrutierend » Google-Maps Ansprechpartner: Jasper van der Lugt, MD, PhD Phone: +31618559694 E-Mail: J.vanderLugt@prinsesmaximacentrum.nl» Ansprechpartner anzeigen Great Ormond Street Hospital WC1N 3JH London United KingdomNoch nicht rekrutierend » Google-Maps Ansprechpartner: Darren Hargrave, MD Phone: 0207 813 8525 E-Mail: darren.hargrave@nhs.net» Ansprechpartner anzeigen Alle anzeigen
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, 18 patients).
Inclusion Criteria: 1. Age: Patients must be ≥ 12 months and ≤ 25 years of age at the time of study enrollment. 2. 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. 3. 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: 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. 4. 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. 5. 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 surgery. 6. 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. 7. 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.Exclusion Criteria: 1. 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. 2. Gastrointestinal Disease: Patients with a history of serious gastrointestinal disease, including inflammatory bowel disease or gastrointestinal perforation 3. 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. 4. 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 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.
Primary outcome: 1. Sustained objective response rate of patients with recurrent/progressive previously irradiated ACP to treatment with systemic tocilizumab (Time Frame - From Day 1 of treatment through 30 days following end of protocol treatment):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). 2. 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 (Time Frame - From Day 1 of treatment through 30 days following end of protocol treatment):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). Secondary outcome: 1. Biological effects of tocilizumab on ACP tumor tissue and cyst fluid. (Time Frame - From Day 1 of treatment through 30 days following end of protocol treatment):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. 2. Toxicities associated with tocilizumab in children with ACP (Time Frame - From Day 1 of treatment through 30 days following end of protocol treatment):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. 3. PFS of ACP patients treated with tocilizumab after radiation (Time Frame - 12 months):To assess one-year progression-free survival (PFS) rates for patients with ACP who are
treated with tocilizumab following progression after radiation (Stratum 1). 4. PFS of ACP patients treated with tocilizumab who have not received radiation (Time Frame - 12 months):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).
Tocilizumab (ACTEMRA®):For < 30 kg: 12 mg/kg IV every 2 weeks; For ≥30 kg: 8 mg/kg IV every 2 weeks
Quelle: ClinicalTrials.gov
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