CompletedPhase 1

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

United States56 participantsStarted 2018-01-02

Plain-language summary

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.

Who can participate

Age range18 Years

SexALL

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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 f…

What they're measuring

Maximum Concentration (Cmax) of Plasma Midazolam on Day -7, Day 1, and Day 14

Timeframe: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14

Cmax of Plasma Total 1-OH Midazolam on Day -7, Day 1, and Day 14

Timeframe: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14

Cmax of Plasma Free 1-OH Midazolam on Day -7, Day 1, and Day 14

Timeframe: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14

Cmax of Plasma Glucuronide Conjugated 1-Hydroxymidazolam on Day -7, Day 1, and Day 14

Timeframe: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14

Cmax of Plasma Absolute Caffeine on Day -7, Day 1, and Day 14

Timeframe: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14

Cmax of Plasma Baseline-Adjusted Caffeine on Day -7, Day 1, and Day 14

Timeframe: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14

Cmax of Plasma Paraxanthine on Day -7, Day 1, and Day 14

Timeframe: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14

Trial details

NCT IDNCT03864042

SponsorPfizer

Sponsor typeINDUSTRY

Study typeINTERVENTIONAL

Primary completion2022-07-11

Results submitted2023-07-07

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