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

NCT03864042

Last updated date
Study Location
Pfizer Investigative Site
Edegem, , 2650, Belgium
Contact
1-800-718-1021

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Contact a representative by phone, email, or visiting the study website. Please see the references below:

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Pfizer Clinical Trials Contact Center

1-800-718-1021

By email

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[email protected]

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Eligibility Criteria
condition
The disease, disorder, syndrome, illness, or injury that is being studied.
Advanced Solid Tumors, Metastatic Melanoma
Sex
Females and Males
Age
Pediatric Trials: 0-17 Years
Adult Trials: 18+ Years
18 + years
Inclusion Criteria
The factors, or reasons, that allow a person to participate in a clinical study.
Show details

- 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
The factors, or reasons, that prevent a person from participating in a clinical study.
Show details

- 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;

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Pfizer Clinical Trials Contact Center

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Advanced Solid Tumors, Metastatic MelanomaPharmacokinetic Drug-drug Interaction Study of Encorafenib and Binimetinib on Probe Drugs in Patients With BRAF V600-mutant Melanoma or Other Advanced Solid Tumors
NCT03864042
  1. Edegem,
  2. Liège,
  3. Mechelen,
  4. Edmonton, Alberta
  5. Montréal,
  6. Montréal,
  7. Toronto,
  8. Barcelona,
  9. El Palmar,
  10. Madrid,
  11. Madrid,
  12. Madrid,
  13. Seville,
  14. Valencia,
  15. Fountain Valley, California
  16. Orange, California
  17. Aurora, Colorado
  18. Chicago, Illinois
  19. Saint Paul, Minnesota
  20. Omaha, Nebraska
  21. Canton, Ohio
  22. Knoxville, Tennessee
  23. Dallas, Texas
  24. Salt Lake City, Utah
ALL GENDERS
18 Years+
years
MULTIPLE SITES
Advanced Information
Descriptive Information
Brief Title  ICMJE Pharmacokinetic Drug-drug Interaction Study of Encorafenib and Binimetinib on Probe Drugs in Patients With BRAF V600-mutant Melanoma or Other Advanced Solid Tumors
Official Title  ICMJE An Open-label Phase 1 Study to Evaluate Drug-Drug Interactions of Agents Co-Administered With Encorafenib and Binimetinib in Patients With BRAF V600-mutant Unresectable or Metastatic Melanoma or Other Advanced Solid Tumors
Brief 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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Advanced Solid Tumors
  • Metastatic Melanoma
Intervention  ICMJE
  • Drug: losartan
    taken orally
  • Drug: dextromethorphan
    taken orally
  • Drug: caffeine
    taken orally
  • Drug: omeprazole
    taken orally
  • Drug: midazolam
    taken orally
  • Drug: rosuvastatin
    taken orally
  • Drug: bupropion immediate release (IR)
    taken orally
  • Drug: encorafenib
    taken orally
  • Drug: binimetinib
    taken orally
  • Drug: modafinil
    taken orally
Study Arms  ICMJE
  • Experimental: Arm 1 - CYP Probe Cocktail

    Patients will receive a single oral dose of the CYP Probe Cocktail on Day -7, Day 1, and Day 14:

    • 25 mg losartan oral tablet
    • 30 mg (2 x 15 mg) dextromethorphan oral capsule
    • 50 mg caffeine 20 mg/mL oral liquid
    • 20 mg omeprazole oral capsule
    • 2 mg midazolam 2 mg/mL oral syrup

    encorafenib/binimetinib continuous daily dosing starting Day 1:

    • 450 mg (6 x 75 mg) encorafenib oral capsules once daily (QD)
    • 45 mg (3 x 15 mg) binimetinib oral tablet twice daily (BID)

    All drugs will be taken within 10 minutes.

    Interventions:
    • Drug: losartan
    • Drug: dextromethorphan
    • Drug: caffeine
    • Drug: omeprazole
    • Drug: midazolam
    • Drug: encorafenib
    • Drug: binimetinib
  • Experimental: Arm 2 - Rosuvastatin and Bupropion

    Patients will receive a single oral dose of rosuvastatin and bupropion once on Day -7, Day 1 and Day 14:

    • 10 mg rosuvastatin oral tablet
    • 75 mg bupropion immediate release (IR) oral tablet

    encorafenib/binimetinib continuous daily dosing starting Day 1:

    • 450 mg (6 x 75 mg) encorafenib oral capsules once daily (QD)
    • 45 mg (3 x 15 mg) binimetinib oral tablet twice daily (BID)

    All drugs will be taken within 10 minutes.

    Interventions:
    • Drug: rosuvastatin
    • Drug: bupropion immediate release (IR)
    • Drug: encorafenib
    • Drug: binimetinib
  • Experimental: Arm 3 - Modafinil

    Patients will begin encorafenib/binimetinib continuous daily dosing starting Day 1:

    • 450 mg (6 x 75 mg) encorafenib oral capsules once daily (QD)
    • 45 mg (3 x 15 mg) binimetinib oral tablet twice daily (BID)

    then receive continuous treatment of modafinil on Day 15 through Day 21:

    - 400 mg (2 × 200 mg) modafinil tablet once daily (QD)

    Interventions:
    • Drug: encorafenib
    • Drug: binimetinib
    • Drug: modafinil
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: March 4, 2019)
42
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE August 19, 2022
Estimated Primary Completion Date August 19, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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;
Sex/Gender  ICMJE
Sexes Eligible for Study:All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Pfizer CT.gov Call Center1-800-718-1021[email protected]
Listed Location Countries  ICMJE Belgium,   Canada,   Spain,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03864042
Other Study ID Numbers  ICMJE ARRAY-818-103
C4221003 ( Other Identifier: Pfizer )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD:No
Plan Description:Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/d….
Responsible Party Pfizer
Study Sponsor  ICMJE Pfizer
Collaborators  ICMJE Pierre Fabre Laboratories
Investigators  ICMJE
Study Director:Pfizer CT.gov Call CenterPfizer
PRS Account Pfizer
Verification Date June 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP