Phase
Condition
Multiple Myeloma
Hematologic Neoplasms
Melanoma
Treatment
Vemurafenib
Cobimetinib
Clinical Study ID
Ages > 18 All Genders
Study Summary
Eligibility Criteria
Inclusion
Inclusion Criteria:
A. Confirmed diagnosis of a malignancy harbouring any actionable BRAF V600 mutation usingan analytically validated sequencing technique (result does not need to be confirmed atscreening unless not tested within 18 months, in which case, repeat analysis is required).
B. Adult patients ≥16 years old. C. Patients must be able and willing to undergo a fresh biopsy. D. Adequate organ function as per haematological and biochemical indices within the rangesshown below. These measurements should be performed to confirm the patient's eligibility. Haemoglobin (Hb): ≥90 g/L (transfusion allowed) Absolute neutrophil count (ANC): ≥1.5×10^9/L (no granulocyte colony-stimulating factor [GCSF] support in preceding 72 hours) Platelet count: ≥100×10^9/L (unsupported for 72 hours) Bilirubin: <1.5 x upper limit of normal (ULN) Patients with known Gilbert disease: total bilirubin ≤3.0 x ULN Alanine aminotransferase (ALT) and aspartate aminotransferase (AST): ≤2.5 x ULN or ≤ 5 ULNif raised due to presence of liver metastases estimated glomerular filtration rate (eGFR): ≥30 mL/min (uncorrected value) Coagulation- Prothrombin (PT) (or international normalized ratio (INR), and activatedpartial thromboplastin clotting time (aPTT): INR or PT ≤1.5 and aPTT <1.5x ULN (unlesspatient is on anticoagulants e.g. warfarin [INR should be stable and within therapeuticrange], or direct oral anticoagulants [DOAC] Electrolytes- Potassium (K), Magnesium (Mg) and Calcium (Ca): Electrolytes within normalrange (electrolyte replacement permitted)
E. Women of childbearing potential are eligible provided that they meet the followingcriteria:
- Have a negative serum or urine pregnancy test before enrolment and;
- Agree to use any two forms of highly effective or effective methods together (at leastone to be non-hormonal) such as:
- Highly effective methods:
- combined (oestrogen and progestogen containing) hormonal contraception associated withinhibition of ovulation (oral, intravaginal, transdermal)
- progestogen-only hormonal contraception associated with inhibition of ovulation (oral,injectable, implantable)
- intrauterine device (IUD)
- intrauterine hormone-releasing system (IUS)
- bilateral tubal occlusion
- vasectomised partner
- sexual abstinence
- Effective methods:
- progestogen-only oral hormonal contraception not associated with inhibition ofovulation
- male or female condom with or without spermicide
- cap, diaphragm or sponge with spermicide Effective from the first administration of vemurafenib or cobimetinib (whichever is first),throughout the trial and for six months after the last administration of vemurafenib orcobimetinib (whichever is later).
F. Male patients with partners who are women of childbearing potential, are eligibleprovided that they agree to the following, from the first administration of vemurafenib orcobimetinib (whichever is first), throughout the trial and for six months after the lastadministration of vemurafenib or cobimetinib (whichever is later):
- Agree to take measures not to father children by using a barrier method ofcontraception (condom plus spermicide) or to sexual abstinence
- Non-vasectomised male patients with partners who are women of childbearing potentialmust also be willing to ensure that their partner uses a highly effective method ofcontraception as in E, above.
- Male patients with pregnant or lactating partners must be advised to use barriermethod contraception (for example, condom plus spermicide) to prevent drug exposure ofthe foetus or neonate.
Exclusion
Exclusion Criteria:
A. Diagnosis of unresectable or metastatic melanoma with a BRAF V600 mutation.
B. Female patients who are pregnant, breastfeeding or planning to become pregnant duringthe trial or for six months following their last dose of vemurafenib or cobimetinib,whichever is later. C. Patients with QTcF (Corrected QT interval by Fridericia) at screening of >450ms formales and >470ms for females measured on triplicate ECG (if 1/3 readings show >450/470msthen patient is ineligible). D. Patients with any history of long QT syndrome or Torsades de Pointes (or any concurrentmedication with a known risk of inducing Torsades de Pointes).
E. Known hypersensitivity to vemurafenib or cobimetinib or any of the excipients.
F. Patients with clinically significant pre-existing cardiac conditions including (withinthe last three months prior to screening):
- Uncontrolled or symptomatic angina,
- Uncontrolled atrial or ventricular arrhythmias,
- Class III & IV New York Heart Association (NYHA) congestive heart failure,
- Left ventricular ejection fraction (LVEF) <50%,
- Myocardial infarction
G. Ophthalmological disorders: History of retinal detachment, severe visual impairment,central serous chorioretinopathy, neovascular retinopathy, or retinopathy of prematurity. Patients with low grade gliomas causing visual impairment may be considered eligible andmonitored with close ophthalmological monitoring.
H. History of pancreatitis. I. History of central nervous system (CNS) or gastrointestinal (GI) haemorrhage withinthree months of trial entry.
J. Patients with any history of haemorrhagic stroke.
K. Prior treatment with the same class of drug unless presence of a resistance alterationknown to be potentially sensitive to either vemurafenib or cobimetinib. Prior sorafenib useis permissible following a washout period of 10 days. L. Patients with rapidly progressing or symptomatically deteriorating brain metastases.Patients with previously treated brain metastases are eligible, provided the patient hasnot experienced a seizure or had a clinically significant change in neurological statuswithin the 14 days prior to the start of IMP administration. Such patients must benon-dependent on steroids or on a stable or reducing dose of steroid treatment for at least 14 days prior to the start of IMP administration. Primary brain or CNS malignancies areallowed providing the patient is clinically stable (if requiring corticosteroids must be atstable or decreasing doses for at least 14 days prior to the start of IMP administration).Patients who have received brain irradiation must have completed whole-brain radiotherapyand/or stereotactic radiosurgery at least 14 days prior to the start of IMP administration. M. Any clinically significant concomitant disease or condition (or it's treatment) thatcould interfere with, the conduct of the trial or absorption of oral medications thatwould, in the opinion of the Investigator, pose an unacceptable risk to the patient in thistrial.
Study Design
Study Description
Connect with a study center
Belfast City Hospital
Belfast, BT9 7AB
United KingdomSite Not Available
University Hospital Birmingham
Birmingham, B15 2TT
United KingdomActive - Recruiting
Bristol Haematology and Oncology Centre
Bristol, BS2 8ED
United KingdomSite Not Available
Addenbrooke's Hospital
Cambridge, CB2 OQQ
United KingdomActive - Recruiting
Velindre Cancer Centre
Cardiff, CF14 2TL
United KingdomSite Not Available
Western General Hospital
Edinburgh, EH4 2XU
United KingdomActive - Recruiting
The Beatson Hospital
Glasgow, G12 OYN
United KingdomActive - Recruiting
Leeds General Infirmary
Leeds, LS1 3EX
United KingdomSite Not Available
Leicester Royal Infirmary
Leicester, LE1 5WW
United KingdomActive - Recruiting
Guy's Hospital
London, SE1 9RT
United KingdomActive - Recruiting
University College London Hospital
London, NW1 2BU
United KingdomSite Not Available
The Christie Hospital
Manchester, M20 4BX
United KingdomActive - Recruiting
Freeman Hospital
Newcastle, NE7 7DN
United KingdomActive - Recruiting
Churchill Hospital
Oxford, OX3 7LE
United KingdomActive - Recruiting
Weston Park Hospital
Sheffield, S10 2SJ
United KingdomSite Not Available
Southampton General Hospital
Southampton, SO16 6YD
United KingdomSite Not Available
Clatterbridge Cancer Centre
Wirral, CH63 4JY
United KingdomSite Not Available
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