Status:
RECRUITING
Encorafenib, Binimetinib and Palbociclib in BRAF-mutant Metastatic Melanoma CELEBRATE
Lead Sponsor:
Peter MacCallum Cancer Centre, Australia
Conditions:
Melanoma
Metastasis
Eligibility:
All Genders
18-100 years
Phase:
PHASE1
PHASE2
Brief Summary
This is an open-label, phase IB, non-randomised study consisting of a dose escalation phase and expansion phase, evaluating the safety, tolerability and preliminary efficacy of the combination of enco...
Detailed Description
This is an open-label, multicentre, Phase IB, dose escalation study with dose expansion designed to assess the safety, tolerability, and pharmacokinetics of the encorafenib, binimetinib and palbocicli...
Eligibility Criteria
Inclusion
- Dose Escalation Phase only: (Australia only)
- 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)
- 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.
- 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):
- Patients (male and female) age ≥ 18 years
- Has provided written informed consent prior to any screening procedure
- Histologically confirmed diagnosis of unresectable stage III or IV melanoma (stage IIIB to IV per American Joint Committee on Cancer \[AJCC\] 8th edition).
- Documented evidence of BRAF V600 mutation.
- 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.
- 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.
- 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
- ECOG Performance Status ≤ 2
- Able to take oral medications
- Be willing and able to comply with all study requirements, including treatment, attending assessments and follow-up.
- 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.
- 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.
Exclusion
- Patients with uveal melanoma.
- 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).
- Patients receiving enzyme inducing anti-epileptic drugs (as listed in Appendix 5).
- History of acute or chronic pancreatitis.
- 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).
- 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
Key Trial Info
Start Date :
June 4 2020
Trial Type :
INTERVENTIONAL
Allocation :
ESTIMATED
End Date :
December 4 2024
Estimated Enrollment :
78 Patients enrolled
Trial Details
Trial ID
NCT04720768
Start Date
June 4 2020
End Date
December 4 2024
Last Update
January 5 2024
Active Locations (4)
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1
Box Hill Hospital
Box Hill, Victoria, Australia, 3128
2
Austin Hospital
Heidelberg, Victoria, Australia, 3084
3
Peter MacCallum Cancer Centre
Melbourne, Victoria, Australia, 3000
4
Alfred Health
Melbourne, Victoria, Australia, 3004