Pharmacokinetic Drug-drug Interaction Study of Encorafenib and Binimetinib on Probe Drugs in Patients With BRAF V600-mutant Melanoma or Other Advanced Solid Tumors



Status:Recruiting
Conditions:Skin Cancer, Cancer
Therapuetic Areas:Oncology
Healthy:No
Age Range:18 - Any
Updated:3/8/2019
Start Date:January 2, 2018
End Date:December 2024
Contact:Array BioPharma, Inc
Email:clinicaltrials@arraybiopharma.com
Phone:303-381-6604

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An Open-label Phase 1 Study to Evaluate the Effects of Encorafenib in Combination With Binimetinib on the Pharmacokinetics of Losartan, Midazolam, Caffeine, Omeprazole, and Dextromethorphan Administered in a Cocktail Approach and on the Pharmacokinetics of Rosuvastatin in Patients With BRAF V600-mutant Unresectable or Metastatic Melanoma or Other Advanced Solid Tumors

This is an open-label, 3-arm, fixed-sequence study to evaluate the effect of single and
multiple oral doses of encorafenib in combination with binimetinib on the single oral dose
pharmacokinetics (PK) of cytochrome P450 (CYP) enzyme probe substrates using a probe
cocktail, on an organic anion-transporting polypeptide/breast cancer resistance protein
(OATP/BCRP) substrate using rosuvastatin and on a CYP2B6 substrate using bupropion. The
effect of multiple oral doses of the moderate cytochrome P450 (CYP) inhibitor modafinil on
encorafenib in combination with binimetinib will also be assessed. The study will have 2
treatment phases, a drug-drug interaction (DDI) phase followed by a post-DDI phase.


Key Inclusion Criteria - Patients must meet all of the inclusion criteria to be eligible
for enrollment into the study:

- Histologically confirmed diagnosis of locally advanced, unresectable or metastatic
cutaneous melanoma or unknown primary melanoma American Joint Committee on Cancer
(AJCC) Stage IIIB, IIIC or IV; or other BRAF V600-mutant advanced solid tumors

- Presence of BRAF V600E and/or V600K mutation in tumor tissue prior to enrollment, as
determined using a local test;

- Evidence of measurable or non-measurable lesions

- Patient with unresectable locally advanced or metastatic melanoma who has received no
prior treatment or progressed on or after prior systemic therapy; Note: Prior therapy
with a BRAF proto-oncogene serine-threonine protein kinase (BRAF) inhibitor and/or a
mitogen-activated protein (MAP) kinase (MEK) inhibitor is permitted except in the
regimen immediately prior to study entry

- Patient with other (non-melanoma) BRAF V600E and/or V600K -mutant advanced solid
tumors who has progressed on standard therapy or for whom there are no available
standard therapies; Note: Prior therapy with a BRAF inhibitor and/or a MEK inhibitor
is permitted except in the regimen immediately prior to study entry

- Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1

- Adequate bone marrow, hepatic and renal function as specified in the protocol

- ARM 1 ONLY: Non-smoker who has not used nicotine containing products for at least 3
months prior to the first dose.

Key Exclusion Criteria - Patients meeting any of the following criteria are not eligible
for enrollment in the study:

- Symptomatic brain metastasis. Patients previously treated or untreated for these
conditions that are asymptomatic in the absence of corticosteroid and anti-epileptic
therapy are allowed. Brain metastases must be stable, with imaging (e.g., magnetic
resonance imaging [MRI] or computed tomography [CT] demonstrating no current evidence
of progressive brain metastases at screening);

- Symptomatic or untreated leptomeningeal disease;

- 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);

- Clinically significant cardiac disease

- Known hyper-coagulability risks other than malignancy (e.g., Factor V Leiden
syndrome);

- Thromboembolic event except catheter-related venous thrombosis ≤ 12 weeks prior to
starting study treatment.

- Discontinuation of prior BRAF and/or MEK inhibitor treatment due to left ventricular
dysfunction, pneumonitis/interstitial lung disease, or retinal vein occlusion;

- ARM 1 ONLY: Positive urine cotinine test at screening

- ARM 3 ONLY:

- History of psychosis, depression or mania;

- History of angioedema;

- History of mitral valve prolapse;

- History of left ventricular hypertrophy;
We found this trial at
10
sites
8303 Dodge Street
Omaha, Nebraska 68114
(402) 354–4000
Principal Investigator: Ralph Hauke, MD
Phone: 402-354-5831
Nebraska Methodist Hospital Methodist Hospital is a general medical and surgical hospital in Omaha, NE....
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Aurora, Colorado 80045
Principal Investigator: Karl Lewis, MD
Phone: 720-848-7135
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Canton, Ohio 44718
Principal Investigator: Nashat Y Gabrail, MD
Phone: 330-492-3345
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Chicago, Illinois 60612
Principal Investigator: Rozina Chowdhery, MD
Phone: 312-355-5512
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7777 Forest Lane
Dallas, Texas 75230
Principal Investigator: James Strauss, MD
Phone: 972-566-3082
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Fountain Valley, California 92708
Principal Investigator: Haresh S Jhangiani, MD
Phone: 714-698-0300
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Knoxville, Tennessee 37920
Principal Investigator: Timothy J Panella, MD
Phone: 865-305-7915
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Orange, California 92868
Principal Investigator: John Fruehauf, MD, PhD
Phone: 877-827-8839
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Orange, CA
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640 Jackson Street
Saint Paul, Minnesota 55101
651-254-3456
Principal Investigator: Arkadiusz Dudek, MD
Phone: 651-254-1517
Regions Hospital Established in 1872, Regions Hospital is a private, not-for-profit organization. The hospital provides...
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Salt Lake City, Utah 84106
Principal Investigator: Justin Call, MD
Phone: 801-281-6864
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