AzTrials
AzTrials

MelanomaPhase 1NCT03878719

Study of the Combination of Binimetinib and Encorafenib in Adolescent Patients With Unresectable or Metastatic BRAF V600-mutant Melanoma

A Phase 1 study testing binimetinib and encorafenib in people with Melanoma, run by Pfizer at 1 site in Italy.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
Search all trials

Trial summary

This is a multicenter Phase 1b, open-label study to evaluate the pharmacokinetic, safety and efficacy of binimetinib and encorafenib co-administered to adolescent patients with BRAF V600-mutant advanced/metastatic melanoma. Read more about this study

Who is it for?
Ages 12 to 17 years
Conditions the study is for
Melanoma
What is being tested?
binimetinib and encorafenib
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
1 participants
Where
1 siteItaly
Study dates
3 Aug 2020to 19 Aug 2022
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 12 to 17 years
  • All sexes
  • No healthy volunteers
  • Child

Who may be able to join

  • Patients must meet all of the following criteria to be eligible for enrollment in the study.
  • Histologically confirmed diagnosis of locally advanced, unresectable or metastatic cutaneous melanoma or unknown primary melanoma American Joint Committee on Cancer Stage IIIB, IIIC, or IV.
  • Presence of BRAF V600E or V600K mutation in tumor tissue as determined by a local or central laboratory
  • Adequate cardiac function:
  • Left ventricular ejection fraction (LVEF) ≥ 50% as determined by ECHO or multi-gated acquisition (MUGA) scan and above the institutional lower limit of normal (LLN);
  • Triplicate average baseline QTcF value ≤ 450 ms.
Show all 16Show fewer
  • Adequate bone marrow, organ function, and laboratory parameters:
  • Absolute neutrophil count (ANC) ≥ 1.5 × 10⁹/L;
  • Hemoglobin ≥ 9 g/dL with or without transfusions;
  • Platelets ≥ 75 × 10⁹/L without transfusions;
  • Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) ≤ 2.5 × upper limit of normal (ULN); in patients with liver metastases ≤ 5 × ULN;
  • Total bilirubin ≤ 1.5 × ULN;
  • Creatinine ≤ 1.5 × institutional ULN for age, or calculated creatinine clearance ≥ 70 mL/min/1.73 m² (following Schwartz formula).
  • Adequate performance status at Screening:
  • Patients < 16 years old: Lansky Performance Scale score ≥ 80
  • Patients 16 to 17 years old: Karnofsky Performance Scale score ≥ 80

Who cannot join

  • Patients meeting any of the following criteria are not eligible for enrollment in the study.
  • Uveal or mucosal melanoma.
  • Brain metastases that are uncontrolled or symptomatic, require steroids, are potentially life-threatening or have required radiation within 28 days prior to starting study drug.
  • History or current evidence of retinal vein occlusion (RVO) or current risk factors for RVO
  • Prior therapy with a BRAF inhibitor (e.g., dabrafenib, vemurafenib) and/or a MEK inhibitor (e.g., trametinib, cobimetinib).
  • Impaired cardiovascular function or clinically significant cardiovascular disease, including any of the following:
Show all 11Show fewer
  • History of acute coronary syndromes (including myocardial infarction, unstable angina, coronary artery bypass grafting, coronary angioplasty or stenting) < 6 months prior to screening,
  • Symptomatic chronic heart failure, history or current evidence of clinically significant cardiac arrhythmia and/or conduction abnormality < 6 months prior to screening except atrial fibrillation and paroxysmal supraventricular tachycardia.
  • Concurrent neuromuscular disorder associated with elevated creatine kinase (CK)
  • Uncontrolled arterial hypertension despite medical treatment
  • Presence of BRAFʷͭ or indeterminate melanoma in tumor tissue.

Trial locations and contacts

1 site in 1 country.

Italy1 site

  • Fondazione IRCCS Istituto Nazionale Dei Tumori

    Milan, Lombardy, 20133

Other trials in Italy

About this study

Official title: A Multicenter, Open-label Phase 1b Study of the Combination of Binimetinib and Encorafenib in Adolescent Patients With Unresectable or Metastatic BRAF V600-mutant Melanoma

This is a multicenter Phase 1b, open-label study to evaluate the pharmacokinetic, safety and efficacy of binimetinib and encorafenib co-administered to adolescent patients with BRAF V600-mutant advanced/metastatic melanoma. The study consists of a Safety Run-in Phase to determine the RDE (recommended dose in expansion), followed by an Expansion Phase.

Read the detailed description

The study did not recruit the desired number of subjects and as a result does not have sufficient data for quantitative statistical analyses. Additionally, results data cannot be reported because doing so would risk re-identification of the participant.

Conditions
Melanoma
Being tested
binimetinib, encorafenib
Keywords
Adolescent, BRAF V600K, BRAF V600E
Medical subject headings
Melanoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • binimetinibDrug

    taken orally

  • encorafenibDrug

    taken orally

Study groups in NCT03878719
Study groupRoleWhat they receive
Safety Run-in PhaseExperimental* binimetinib taken twice daily (BID) and * encorafenib taken once daily (QD) Dose levels by patient body surface area (BSA) for binimetinib and encorafenib tablets/capsules are specified in the protocol.
Receives: Drug: binimetinib; Drug: encorafenib
Expansion PhaseExperimental* binimetinib taken twice daily (BID) and * encorafenib taken once daily (QD) Dose levels by patient body surface area (BSA) for binimetinib and encorafenib tablets/capsules and pediatric formulations are specified in the protocol.
Receives: Drug: binimetinib; Drug: encorafenib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Pharmacokinetic (PK) parameter (time to reach the maximum observed plasma concentration Cmax [Tmax]) for binimetinib

    Measured: Day 1 and Day 15 of Cycle 1, 28 day cycles

  2. PK parameter (Cmax) for binimetinib

    Measured: Day 1 and Day 15 of Cycle 1, 28 day cycles

  3. PK parameter (time of last PK sample [Tlast]) for binimetinib

    Measured: Day 1 and Day 15 of Cycle 1, 28 day cycles

  4. PK parameter (area under the plasma concentration-time curve from time zero to Tlast [AUClast]) for binimetinib

    Measured: Day 1 and Day 15 of Cycle 1, 28 day cycles

  5. PK parameter (Tmax) for binimetinib's active metabolite (AR00426032)

    Measured: Day 1 and Day 15 of Cycle 1, 28 day cycles

  6. PK parameter (Cmax) for AR00426032

    Measured: Day 1 and Day 15 of Cycle 1, 28 day cycles

  7. PK parameter (Tlast) for AR00426032

    Measured: Day 1 and Day 15 of Cycle 1, 28 day cycles

  8. PK parameter (AUClast) for AR00426032

    Measured: Day 1 and Day 15 of Cycle 1, 28 day cycles

  9. PK parameter (Tmax) for encorafenib

    Measured: Day 1 and Day 15 of Cycle 1, 28 day cycles

  10. PK parameter (Cmax) for encorafenib

    Measured: Day 1 and Day 15 of Cycle 1, 28 day cycles

  11. PK parameter (Tlast) for encorafenib

    Measured: Day 1 and Day 15 of Cycle 1, 28 day cycles

  12. PK parameter (AUClast) for encorafenib

    Measured: Day 1 and Day 15 of Cycle 1, 28 day cycles

  13. PK parameter (Tmax) for encorafenib's metabolite (LHY746)

    Measured: Day 1 and Day 15 of Cycle 1, 28 day cycles

  14. PK parameter (Cmax) for LHY746

    Measured: Day 1 and Day 15 of Cycle 1, 28 day cycles

  15. PK parameter (Tlast) for LHY746

    Measured: Day 1 and Day 15 of Cycle 1, 28 day cycles

  16. PK parameter (AUClast) for LHY746

    Measured: Day 1 and Day 15 of Cycle 1, 28 day cycles

  17. PK parameter (trough concentration [Ctrough]) for binimetinib

    Measured: at time zero Day 15 of Cycle 1, 28 day cycles

  18. PK parameter (trough concentration [Ctrough]) for binimetinib

    Measured: at time zero Day 1 of Cycle 2, 28 day cycles

  19. PK parameter (trough concentration [Ctrough]) for binimetinib

    Measured: at time zero Day 1 of Cycle 3, 28 day cycles

  20. PK parameter (Ctrough) for AR00426032

    Measured: at time zero Day 15 of Cycle 1, 28 day cycles

  21. PK parameter (Ctrough) for AR00426032

    Measured: at time zero Day 1 of Cycle 2, 28 day cycles

  22. PK parameter (Ctrough) for AR00426032

    Measured: at time zero Day 1 of Cycle 3, 28 day cycles

  23. PK parameter (Ctrough) for encorafenib

    Measured: at time zero Day 15 of Cycle 1, 28 day cycles

  24. PK parameter (Ctrough) for encorafenib

    Measured: at time zero Day 1 of Cycle 2, 28 day cycles

  25. PK parameter (Ctrough) for encorafenib

    Measured: at time zero Day 1 of Cycle 3, 28 day cycles

  26. PK parameter (Ctrough) for LHY746

    Measured: at time zero Day 15 of Cycle 1, 28 day cycles

  27. PK parameter (Ctrough) for LHY746

    Measured: at time zero Day 1 of Cycle 2, 28 day cycles

  28. PK parameter (Ctrough) for LHY746

    Measured: at time zero Day 1 of Cycle 3, 28 day cycles

Secondary outcomes (12)

  1. Incidence and severity of adverse events (AEs)

    Measured: From informed consent up to 30 days following last dose of study drug

  2. Incidence of dose-limiting toxicities (DLTs)

    Measured: Duration of treatment for safety run-in phase, approximately 6 months, 28 day cycles

  3. Palatability score for the pediatric formulations as assessed by an age-appropriate questionnaire for binimetinib

    Five-point Hedonic scale from 1 to 5, 5=really good

    Measured: Through Cycle 3 Day 1 in patients receiving the pediatric formulations in the Expansion Phase, 28 day cycles

  4. Palatability score for the pediatric formulations as assessed by an age-appropriate questionnaire for encorafenib

    Five-point Hedonic scale from 1 to 5, 5=really good

    Measured: Through Cycle 3 Day 1 in patients receiving the pediatric formulations in the Expansion Phase, 28 day cycles

  5. Objective response rate (ORR) assessed by the investigator, based on Response Criteria Evaluation in Solid Tumors (RECIST) v1.1

    Measured: Duration of treatment, approximately 6 months, 28 day cycles

  6. Duration of response (DOR)

    Measured: Duration of treatment, approximately 6 months, 28 day cycles

  7. Time to response

    Measured: Duration of treatment, approximately 6 months, 28 day cycles

  8. Progression-free survival (PFS)

    Measured: Duration of treatment, approximately 6 months, 28 day cycles

  9. One-year survival rate

    Measured: From first dose up to 1 year after treatment initiation

  10. Change from baseline bone age and the difference in bone age and chronological age

    Measured: Duration of treatment, approximately 6 months, 28 day cycles

  11. Change from Baseline in bone densitometry based on dual energy X-ray absorptiometry (DEXA) scan.

    Measured: Duration of treatment, approximately 6 months, 28 day cycles

  12. Change from Baseline in calcium-phosphorus product (Ca × P)

    Measured: Duration of treatment, approximately 6 months, 28 day cycles

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted18 Mar 2019
  2. Study start3 Aug 2020
  3. Primary completion19 Aug 2022
  4. Study completion19 Aug 2022

Why it stopped: The trial was terminated early on 05 October 2022 due to non-feasibility and poor recruitment and not based on safety concerns.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
1 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03878719
Sponsor's protocol ID
ARRAY-162-115
Other IDs
C4221011, 2018-001946-32, 2018
Status last verified
Mar 2023
First submitted
20 Feb 2019
Last updated
3 Apr 2023
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No: 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/data\_requests.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing binimetinib and encorafenib in people with Melanoma, run by Pfizer at 1 site in Italy.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 16 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 3 Apr 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: The trial was terminated early on 05 October 2022 due to non-feasibility and poor recruitment and not based on safety concerns.). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Pharmacokinetic (PK) parameter (time to reach the maximum observed plasma concentration Cmax [Tmax]) for binimetinib (time frame: Day 1 and Day 15 of Cycle 1, 28 day cycles). The study lists 28 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03878719.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Apr 2023.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in