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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04720768




Registration number
NCT04720768
Ethics application status
Date submitted
15/09/2020
Date registered
22/01/2021

Titles & IDs
Public title
Encorafenib, Binimetinib and Palbociclib in BRAF-mutant Metastatic Melanoma CELEBRATE
Scientific title
A Phase 1B Study to Evaluate the Safety, Tolerability and Preliminary Efficacy of the Combination of Encorafenib, Binimetinib and Palbociclib in Patients With BRAF-mutant Metastatic Melanoma (The CELEBRATE Study)
Secondary ID [1] 0 0
17/021
Universal Trial Number (UTN)
Trial acronym
CELEBRATE
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Melanoma 0 0
Metastasis 0 0
Condition category
Condition code
Cancer 0 0 0 0
Malignant melanoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Binimetinib
Treatment: Drugs - Encorafenib
Treatment: Drugs - Palbociclib

Experimental: Dose escalation phase - Encorafenib (tablet) 450mg PO daily

Binimetinib (tablet) 45mg PO BD

Palbociclib (tablet) variable dose PO daily for 21 consecutive days on treatment, followed by 7 consecutive days off treatment in a 28 day cycle


Treatment: Drugs: Binimetinib
MEK inhibitor

Treatment: Drugs: Encorafenib
BRAF inhibitor

Treatment: Drugs: Palbociclib
CDK4/6 inhibitor
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Dose-limiting toxicity (DLTs)
Timepoint [1] 0 0
The assessment period of DLT for each patient is the first cycle (28 days) of treatment
Secondary outcome [1] 0 0
Adverse events (AEs) of Encorafenib, Binimetinib and Palbociclib
Timepoint [1] 0 0
Trough study completion, up until 12 months after last patient commences treatment
Secondary outcome [2] 0 0
Tolerability as defined 80% compliance with each of Encorafenib, Binimetinib and Palbociclib individually.
Timepoint [2] 0 0
28 days for encorafenib and binimetinib, 21 days for palbociclib
Secondary outcome [3] 0 0
Clinical effficacy defined by response
Timepoint [3] 0 0
8 weeks after commencement of treatment
Secondary outcome [4] 0 0
Clinical efficacy as defined by time to progression
Timepoint [4] 0 0
From the date of registration until the date of disease progression
Secondary outcome [5] 0 0
Clinical efficacy as defined by progression free survival
Timepoint [5] 0 0
From the date of registration until the date of first documented disease progression or date of death due to any cause, whichever occurs first (up to approximately 18 months)
Secondary outcome [6] 0 0
Clinical efficacy as defined by overall survival
Timepoint [6] 0 0
From start of treatment until the date of death from any cause, up to approximately 18months)

Eligibility
Key inclusion criteria
Dose Escalation Phase only: (Australia only)

1. Patients who are naïve to, or have received prior BRAF and MEK inhibitor combination therapy. Prior treatment with chemotherapy and biological therapy (e.g. checkpoint inhibitor therapy) is permitted.

Dose Expansion Phase only: (All sites)
2. Cohort 1: Patients who are naïve to BRAF and MEK inhibitor therapy. Prior treatment with chemotherapy and biological therapy (e.g. checkpoint inhibitor therapy) is permitted.
3. Cohort 2: Patients who have progressed on prior BRAF and MEK inhibitor combination therapy. Prior treatment with chemotherapy and biological therapy (e.g. checkpoint inhibitor therapy) is permitted.

For both phases (All sites):
4. Patients (male and female) age = 18 years
5. Has provided written informed consent prior to any screening procedure
6. Histologically confirmed diagnosis of unresectable stage III or IV melanoma (stage IIIB to IV per American Joint Committee on Cancer [AJCC] 8th edition).
7. Documented evidence of BRAF V600 mutation.
8. Patients must provide either archival or newly obtained tumour sample at baseline. In addition, patients must agree to a mandatory biopsy during treatment and at the time of progression, if not medically contraindicated.
9. Evidence of measurable disease, as determined by RECIST v1.1. Note: Lesions in areas of prior radiotherapy or other locoregional therapies (e.g., percutaneous ablation) should not be considered measurable, unless lesion progression has been documented since the therapy.
10. Patients must have adequate haematological, coagulation, renal and hepatic functions as defined by:

Absolute neutrophil count = 1.5 x 109/L Haemoglobin = 10 g/L without transfusions Platelet count = 100 x 109/L without transfusions Total serum creatinine = 1.5 x ULN or calculated or directly measured CrCl < 50% LLN (lower limit of normal) Serum total bilirubin = 1.5 x ULN ( 3 x ULN in cases of known Gilbert's syndrome) AST/SGOT or ALT/SGPT ? 3 x ULN, or ? 5 x ULN if liver metastases are present PT/INR or aPTT < 1.5xULN
11. ECOG Performance Status = 2
12. Able to take oral medications
13. Be willing and able to comply with all study requirements, including treatment, attending assessments and follow-up.
14. Female patients of childbearing potential must have a negative serum pregnancy test at screening: and be willing to use two methods of birth control or be surgically sterile: or abstain from heterosexual activity for the course of the study through to 3 months after the last dose of study medication. Patients of childbearing potential are those who have not been surgically sterilised or have not been free from menses for > 1 year.
15. Sexually active males must use a condom during intercourse while taking the study drugs and for 3 months after stopping treatment and should not father a child in this period. A condom is required to be used also by vasectomised men in order to prevent delivery of the drug via seminal fluid.
Minimum age
18 Years
Maximum age
100 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Patients with uveal melanoma.
2. Patients with symptomatic or untreated brain metastases or leptomeningeal disease. Patients with previously treated or untreated for brain metastasis that are asymptomatic in the absence of corticosteroid therapy or on a stable dose of steroids for 4 weeks prior to registration are allowed to enroll. Brain metastases must be stable at least 4 weeks prior to registration with verification by imaging (e.g. brain MRI completed at screening demonstrating no current evidence of progressive brain metastases).
3. Patients receiving enzyme inducing anti-epileptic drugs (as listed in Appendix 5).
4. History of acute or chronic pancreatitis.
5. History or current evidence of retinal vein occlusion (RVO) or current risk factors for RVO (e.g. uncontrolled glaucoma or ocular hypertension, history of hyperviscosity or hypercoagulability syndromes).
6. Impaired cardiovascular function or clinically significant cardiac disease including any of the following:

* CHF requiring treatment (NYHA grade = 2)
* LVEF < 50% as determined by MUGA scan or ECHO
* History or presence of clinically significant ventricular arrhythmias or uncontrolled atrial fibrillation
* Clinically significant resting bradycardia
* Unstable angina pectoris = 3 months prior to registration
* Acute Myocardial Infarction (AMI) = 3 months prior to registration
* QTcF > 480 ms
* Any heart disease that requires the use of a cardiac pacemaker or implantable cardioverter defibrillator = 3 months prior to registration
* History of QT syndrome, Brugada syndrome or known

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
Other
Other design features
Phase
Phase 1
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
4/06/2020
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
4/12/2024
Actual
Sample size
Target
78
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
Box Hill Hospital - Box Hill
Recruitment hospital [2] 0 0
Austin Hospital - Heidelberg
Recruitment hospital [3] 0 0
Peter MacCallum Cancer Centre - Melbourne
Recruitment hospital [4] 0 0
Alfred Health - Melbourne
Recruitment postcode(s) [1] 0 0
3128 - Box Hill
Recruitment postcode(s) [2] 0 0
3084 - Heidelberg
Recruitment postcode(s) [3] 0 0
3000 - Melbourne
Recruitment postcode(s) [4] 0 0
3004 - Melbourne

Funding & Sponsors
Primary sponsor type
Other
Name
Peter MacCallum Cancer Centre, Australia
Address
Country

Ethics approval
Ethics application status

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

Contacts
Principal investigator
Name 0 0
Grant McArthur, Prof
Address 0 0
Peter MacCallum Cancer Centre, Australia
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Grant McArthur, Prof
Address 0 0
Country 0 0
Phone 0 0
+61385595000
Fax 0 0
Email 0 0
Grant.McArthur@petermac.org
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
De-identified patient data may be shared with external collaborators at other institutions. Any future data sharing agreement for future research will ensure data security and patient confidentiality in maintained.
When will data be available (start and end dates)?
Available to whom?
Available for what types of analyses?
How or where can data be obtained?


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/NCT04720768