MEKTOVI® for the Treatment of Pediatric Adamantinomatous Craniopharyngioma

NCT05286788 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: CONNECT2108
• Study Type: interventional
• Target: 38
• Locations: 3 countries
• Sites: 10

Brief Summary

MEKTOVI (binimetinib) is an oral, highly selective reversible inhibitor of mitogen-activated extracellular signal regulated kinase 1 (MEK1) and MEK2. The biological activity of binimetinib that has been evaluated bith in vitro and in vivo in a wide variety of tumor types 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.

Conditions

Adamantinous Craniopharyngioma; Recurrent Adamantinomatous Craniopharyngioma

Outcome Measures

Primary Outcomes (2)

• Sustained objective response rate of patients with recurrent/progressive previously irradiated ACP to treatment with oral binimetinib

  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 oral binimetinib (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 oral binimetinib

  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 oral binimetinib (Stratum 2).

  From Day 1 of treatment through 30 days following end of protocol treatment

Secondary Outcomes (4)

• Biological effects of binimetinib on ACP tumor tissue and cyst fluid.

  From Day 1 of treatment through 30 days following end of protocol treatment

• Toxicities associated with tocilizumab in children with ACP

  24 months

• PFS of ACP patients treated with binimetinib after radiation

  12 months

• PFS of ACP patients treated with binimetinib who have not received radiation

  12 months

Study Arms (1)

Stratum 1 and Stratum 2

EXPERIMENTAL

Stratum 1: Patients with progressive or recurrent adamantinomatous craniopharyngiomas following radiation therapy. Stratum 2 (NOT CURRENTLY ENROLLING): Patients with measurable adamantinomatous craniopharyngioma who have undergone surgery but have not previously received radiation therapy. Progressive disease is allowed but not required

Drug: Binimetinib Oral Tablet [Mektovi]

Interventions

Binimetinib Oral Tablet [Mektovi] DRUG

Binimetinib oral continuous dosing 32 mg/m2 PO BID for 4 weeks

Also known as: MEKTOVI

Stratum 1 and Stratum 2

Eligibility Criteria

• Age: 1 Year - 39 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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 (NOT CURRENTLY ENROLLING): 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.
• 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 of cyst fenestration, organ resection, and 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, lumbar punctures, and nasal endoscopy to remove packing.
• Organ Function Requirements

You may not qualify if:

• 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
• Patients who are unable to absorb enteral medications
• Administration via NG/NJ/G-tube is allowed
• 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.
• 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.

Sponsors & Collaborators

• Nationwide Children's Hospital: lead
• Children's Hospital Colorado: collaborator

Study Sites (10)

Children's Hospital Colorado

Aurora, Colorado, 80045, United States

RECRUITING

Children's National Medical Center

Washington D.C., District of Columbia, 20010, United States

RECRUITING

Nicklaus Children's Hospital

Miami, Florida, 33155, United States

RECRUITING

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

RECRUITING

Nationwide Children's Hospital

Columbus, Ohio, 43205, United States

RECRUITING

Sydney Children's Hospital

Randwick, New South Wales, 2031, Australia

RECRUITING

Queensland Children's Hospital

South Brisbane, Queensland, 4101, Australia

RECRUITING

Perth Children's Hospital

Perth, Western Australia, 6000, Australia

RECRUITING

British Columbia Children's Hospital

Vancouver, British Columbia, V6H 3N, Canada

RECRUITING

CHU Sainte-Justine

Montreal, Quebec, Canada

RECRUITING

Related Publications (7)

• Foreman NK, Faestel PM, Pearson J, Disabato J, Poole M, Wilkening G, Arenson EB, Greffe B, Thorne R. Health status in 52 long-term survivors of pediatric brain tumors. J Neurooncol. 1999 Jan;41(1):47-53. doi: 10.1023/a:1006145724500.

  PMID: 10222422 BACKGROUND

• Goldman S, Pollack IF, Jakacki RI, Billups CA, Poussaint TY, Adesina AM, Panigrahy A, Parsons DW, Broniscer A, Robinson GW, Robison NJ, Partap S, Kilburn LB, Onar-Thomas A, Dunkel IJ, Fouladi M. Phase II study of peginterferon alpha-2b for patients with unresectable or recurrent craniopharyngiomas: a Pediatric Brain Tumor Consortium report. Neuro Oncol. 2020 Nov 26;22(11):1696-1704. doi: 10.1093/neuonc/noaa119.

  PMID: 32393959 BACKGROUND

• Apps JR, Carreno G, Gonzalez-Meljem JM, Haston S, Guiho R, Cooper JE, Manshaei S, Jani N, Holsken A, Pettorini B, Beynon RJ, Simpson DM, Fraser HC, Hong Y, Hallang S, Stone TJ, Virasami A, Donson AM, Jones D, Aquilina K, Spoudeas H, Joshi AR, Grundy R, Storer LCD, Korbonits M, Hilton DA, Tossell K, Thavaraj S, Ungless MA, Gil J, Buslei R, Hankinson T, Hargrave D, Goding C, Andoniadou CL, Brogan P, Jacques TS, Williams HJ, Martinez-Barbera JP. Tumour compartment transcriptomics demonstrates the activation of inflammatory and odontogenic programmes in human adamantinomatous craniopharyngioma and identifies the MAPK/ERK pathway as a novel therapeutic target. Acta Neuropathol. 2018 May;135(5):757-777. doi: 10.1007/s00401-018-1830-2. Epub 2018 Mar 14.

  PMID: 29541918 BACKGROUND

• Haston S, Pozzi S, Carreno G, Manshaei S, Panousopoulos L, Gonzalez-Meljem JM, Apps JR, Virasami A, Thavaraj S, Gutteridge A, Forshew T, Marais R, Brandner S, Jacques TS, Andoniadou CL, Martinez-Barbera JP. MAPK pathway control of stem cell proliferation and differentiation in the embryonic pituitary provides insights into the pathogenesis of papillary craniopharyngioma. Development. 2017 Jun 15;144(12):2141-2152. doi: 10.1242/dev.150490. Epub 2017 May 15.

  PMID: 28506993 BACKGROUND

• Bendell JC, Javle M, Bekaii-Saab TS, Finn RS, Wainberg ZA, Laheru DA, Weekes CD, Tan BR, Khan GN, Zalupski MM, Infante JR, Jones S, Papadopoulos KP, Tolcher AW, Chavira RE, Christy-Bittel JL, Barrett E, Patnaik A. A phase 1 dose-escalation and expansion study of binimetinib (MEK162), a potent and selective oral MEK1/2 inhibitor. Br J Cancer. 2017 Feb 28;116(5):575-583. doi: 10.1038/bjc.2017.10. Epub 2017 Feb 2.

  PMID: 28152546 BACKGROUND

• Watanabe K, Otsu S, Hirashima Y, Morinaga R, Nishikawa K, Hisamatsu Y, Shimokata T, Inada-Inoue M, Shibata T, Takeuchi H, Watanabe T, Tokushige K, Maacke H, Shiaro K, Ando Y. A phase I study of binimetinib (MEK162) in Japanese patients with advanced solid tumors. Cancer Chemother Pharmacol. 2016 Jun;77(6):1157-64. doi: 10.1007/s00280-016-3019-5. Epub 2016 Apr 12.

  PMID: 27071922 BACKGROUND

• Patel K, Allen J, Zagzag D, Wisoff J, Radmanesh A, Gindin T, Nicolaides T. Radiologic response to MEK inhibition in a patient with a WNT-activated craniopharyngioma. Pediatr Blood Cancer. 2021 Mar;68(3):e28753. doi: 10.1002/pbc.28753. Epub 2020 Oct 19. No abstract available.

  PMID: 33073916 BACKGROUND

Related Links

• Mektovi prescribing information
• Mektovi product characteristics

MeSH Terms

Conditions

Craniopharyngioma

Interventions

binimetinib

Condition Hierarchy (Ancestors)

Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue

Study Officials

• Holly Lindsay, MD

  Children's Hospital Colorado

  STUDY CHAIR

• Todd C Hankinson, MD

  Children's Hospital Colorado

  STUDY CHAIR

• Maryam Fouladi, MD

  Nationwide Children's Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Kelsey H Troyer, PhD

CONTACT

16147223284; kelsey.troyer@nationwidechildrens.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: MEKTOVI® (binimetinib)

Study Record Dates

• First Submitted: March 1, 2022
• First Posted: March 18, 2022
• Study Start: April 10, 2023
• Primary Completion (Estimated): April 10, 2027
• Study Completion (Estimated): April 10, 2027
• Last Updated: April 8, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

CA (2); US (5); AU (3)