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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT05286788


Additional trial details provided through ANZCTR are available at the end of this record.


Registration number
NCT05286788
Ethics application status
Date submitted
1/03/2022
Date registered
18/03/2022

Titles & IDs
Public title
MEKTOVI® for the Treatment of Pediatric Adamantinomatous Craniopharyngioma
Scientific title
Phase 2 Study of the MEK Inhibitor MEKTOVI® (Binimetinib) for the Treatment of Pediatric Adamantinomatous Craniopharyngioma
Secondary ID [1] 0 0
CONNECT2108
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Adamantinous Craniopharyngioma 0 0
Recurrent Adamantinomatous Craniopharyngioma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Brain
Cancer 0 0 0 0
Bone

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Binimetinib Oral Tablet [Mektovi]

Experimental: Stratum 1 and Stratum 2 - Stratum 1: Patients with progressive or recurrent adamantinomatous craniopharyngiomas following radiation therapy.

Stratum 2: Patients with measurable adamantinomatous craniopharyngioma who have undergone surgery but have not previously received radiation therapy. Progressive disease is allowed but not required


Treatment: Drugs: Binimetinib Oral Tablet [Mektovi]
Binimetinib oral continuous dosing 32 mg/m2 PO BID for 4 weeks
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Sustained objective response rate of patients with recurrent/progressive previously irradiated ACP to treatment with oral binimetinib
Timepoint [1] 0 0
From Day 1 of treatment through 30 days following end of protocol treatment
Primary outcome [2] 0 0
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
Timepoint [2] 0 0
From Day 1 of treatment through 30 days following end of protocol treatment
Secondary outcome [1] 0 0
Biological effects of binimetinib on ACP tumor tissue and cyst fluid.
Timepoint [1] 0 0
From Day 1 of treatment through 30 days following end of protocol treatment
Secondary outcome [2] 0 0
Toxicities associated with tocilizumab in children with ACP
Timepoint [2] 0 0
24 months
Secondary outcome [3] 0 0
PFS of ACP patients treated with binimetinib after radiation
Timepoint [3] 0 0
12 months
Secondary outcome [4] 0 0
PFS of ACP patients treated with binimetinib who have not received radiation
Timepoint [4] 0 0
12 months

Eligibility
Key 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 = 1.5 × institutional upper limit of normal
* AST (SGOT) = 2.5 × institutional upper limit of normal
* ALT (SGPT) = 2.5 × institutional upper limit of normal

Adequate Cardiac Function Defined as:
* Left Ventricular Ejection Fraction greater than the institutional lower limit of normal by echocardiogram
* QTc = 480 msec (by Bazett formula)

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
Minimum age
1 Year
Maximum age
25 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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
* Patients who are unable to swallow, retain or absorb oral medications
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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Not applicable
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
10/04/2023
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
10/04/2027
Actual
Sample size
Target
38
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,WA
Recruitment hospital [1] 0 0
Sydney Children's Hospital - Randwick
Recruitment hospital [2] 0 0
Queensland Children's Hospital - South Brisbane
Recruitment hospital [3] 0 0
Perth Children's Hospital - Perth
Recruitment postcode(s) [1] 0 0
2031 - Randwick
Recruitment postcode(s) [2] 0 0
4101 - South Brisbane
Recruitment postcode(s) [3] 0 0
6000 - Perth
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Colorado
Country [2] 0 0
United States of America
State/province [2] 0 0
District of Columbia
Country [3] 0 0
United States of America
State/province [3] 0 0
Ohio
Country [4] 0 0
Canada
State/province [4] 0 0
Quebec

Funding & Sponsors
Primary sponsor type
Other
Name
Nationwide Children's Hospital
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
Children's Hospital Colorado
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Holly Lindsay
Address 0 0
Children's Hospital Colorado
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Amy K Jones, MSN
Address 0 0
Country 0 0
Phone 0 0
16147223284
Fax 0 0
Email 0 0
connect@nationwidechildrens.org
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT05286788

Additional trial details provided through ANZCTR
Accrual to date
1
Recruiting in Australia
Recruitment state(s)
NSW,QLD,WA
Recruitment hospital [1] 161
Perth Children's Hospital
Recruitment hospital [2] 162
Sydney Children's Hospital
Recruitment hospital [3] 163
Queensland Children's Hospital
Recruitment postcode(s) [1] 161
6009
Recruitment postcode(s) [2] 162
2031
Recruitment postcode(s) [3] 163
4101
Funding & Sponsors
Funding source category [1] 88
Charities/Societies/Foundations
Name [1] 88
Robert Connor Dawes Foundation
Address [1] 88
VIC 3191
Country [1] 88
Australia
Funding source category [2] 89
Charities/Societies/Foundations
Name [2] 89
Carrie Bickmore's Beanies 4 Brain Cancer Foundation
Address [2] 89
VIC 3215
Country [2] 89
Australia
Primary sponsor
Other Collaborative groups
Primary sponsor name
Australia and New Zealand Children's Haematology and Oncology Group (ANZCHOG)
Primary sponsor address
27-31 Wright St
Clayton VIC 3168
Primary sponsor country
Australia
Other collaborator category [1] 90
Other
Name [1] 90
Children's Hospital Colorado
Address [1] 90
13123 E. 16 th Ave., Box B-330, Aurora, CO 80045
Country [1] 90
United States of America
Ethics approval
Ethics application status
Approved
Ethics committee name [1] 65
The Child and Adolescent Health Service Human Research Ethics Committee
Address [1] 65
15 Hospital Ave, Nedlands WA 6009
Country [1] 65
Australia
Date submitted for ethics approval [1] 65
16/08/2022
Approval date [1] 65
21/09/2022
Ethics approval number [1] 65
RGS0000005635
 
Public notes

Contacts
Principal investigator
Title 405 0
Dr
Name 405 0
Santosh Valvi
Address 405 0
Perth Children's Hospital
Country 405 0
Australia
Phone 405 0
+612 645 62222
Fax 405 0
Email 405 0
santosh.valvi@health.wa.gov.au
Contact person for public queries
Title 406 0
Dr
Name 406 0
Santosh Valvi
Address 406 0
Perth Children's Hospital
Country 406 0
Australia
Phone 406 0
+612 645 62222
Fax 406 0
Email 406 0
santosh.valvi@health.wa.gov.au
Contact person for scientific queries
Title 407 0
Dr
Name 407 0
Santosh Valvi
Address 407 0
Perth Children's Hospital
Country 407 0
Australia
Phone 407 0
+612 645 62222
Fax 407 0
Email 407 0
santosh.valvi@health.wa.gov.au