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Metastatic MelanomaPhase 2IMPemBraNCT02625337

Study Comparing Pembrolizumab With Dual MAPK Pathway Inhibition Plus Pembrolizumab in Melanoma Patients

A Phase 2 study testing Pembrolizumab, Dabrafenib and Trametinib in people with Metastatic Melanoma, run by The Netherlands Cancer Institute at 1 site in Netherlands.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial summary

This is a Phase 2 trial consisting of 24 patients receiving the combination of dabrafenib + trametinib + pembrolizumab in 3 different dosing schemes and 8 patients receiving pembrolizumab standard monotherapy. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Metastatic Melanoma
What is being tested?
Pembrolizumab, Dabrafenib and Trametinib
Type of treatment
Surgery or procedure
Could I receive a placebo?
No, everyone receives an active treatment
How many people
32 participants
Where
1 siteNetherlands
Study dates
Jan 2016to Dec 2018
Phase
Phase 2
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 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Adults at least 18 years of age
  • World Health Organization (WHO) Performance Status 0-2
  • Histologically/cytologically confirmed stage IV BRAF V600E or K metastatic melanoma
  • Measurable disease according to RECIST 1.1
  • At least one easy accessible lesion (s.c., lymph node) that can be repeatedly biopsied
  • Patient willing to undergo triple tumor biopsies during screening, at week 6, week 8 (cohorts 2-4 only), week 12, at week 18, and in case of disease progression.
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  • No prior immunotherapy targeting PD-1 or PD-L1 (CTLA-4 targeting therapy is allowed)
  • No prior BRAF and/or MEK targeting therapy
  • No immunosuppressive medications
  • Screening laboratory values must meet the following criteria:
  • WBC ≥ 2.0x109/L, Neutrophils ≥ 1.0x109/L, Platelets ≥ 100 x109/L, Hemoglobin ≥ 5.0 mmol/L Creatinine ≤ 2x ULN AST, ALT ≤ 2.5 x ULN (≤5 x ULN for patients with liver metastases) Bilirubin ≤2 X ULN
  • Female subject of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
  • Women of child bearing potential must agree to use a reliable form of contraceptive during the study treatment period and for at least 120 days following the last dose of study drug
  • Men must agree to the use of male contraception during the study Treatment Period and for at least 180 days after the last dose of study drug.

Who cannot join

  • A potential subject who meets any of the following criteria will be excluded from this study:
  • Is currently participating in or has participated in a study of an investigational agent or using an investigational device within 4 weeks of the first dose of treatment.
  • Presence of symptomatic brain or leptomeningeal metastases; patients with asymptomatic brain metastases detected during screening for this study are allowed to participate in this study
  • Prior PD-1/PD-L1 targeting immunotherapy
  • Has an active automimmune disease requiring systemic treatment within the past 3 months or a documented history of clinically severe autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents. Subjects with vitiligo or resolved childhood asthma/atopy would be an exception to this rule. Subjects that require intermittent use of bronchodilators or local steroid injections would not be excluded from the study. Subjects with hypothyroidism stable on hormone replacement or Sjorgen's syndrome will not be excluded from the study.
  • Has had a prior monoclonal antibody within 4 weeks prior to study day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier.
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  • Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to a previously administered agent.
  • Note: Subjects with ≤ Grade 2 neuropathy are an exception to this criterion and may qualify for the study.
  • Note: If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
  • Has evidence of interstitial lung disease or active, non-infectious pneumonitis.
  • Known history of Human Immunodeficiency Virus;
  • Active infection requiring therapy, positive tests for Hepatitis B surface antigen or Hepatitis C ribonucleic acid (RNA);
  • Has active tuberculosis
  • Has received a live vaccine within 30 days prior to the first dose of trial treatment.
  • Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy. Patients that have had another malignancy, but are free of tumor for more than 2 years are allowed for inclusion.

Trial locations and contacts

1 site in 1 country.

Christian U. Blank, Prof. contact

+31205122570

c.blank@nki.nl

Netherlands1 site, 1 recruiting

  • Antoni van Leeuwenhoek ziekenhuis

    Amsterdam, North Holland, 1066CX

    Christian U. Blank, Prof., c.blank@nki.nl

    Recruiting

Other trials in Netherlands

About this study

Official title: Phase 2 Study Comparing Pembrolizumab With Intermittent/Short-term Dual MAPK Pathway Inhibition Plus Pembrolizumab in Patients Harboring the BRAFV600 Mutation

This is a Phase 2 trial consisting of 24 patients receiving the combination of dabrafenib + trametinib + pembrolizumab in 3 different dosing schemes and 8 patients receiving pembrolizumab standard monotherapy. All patients start with pembrolizumab standard therapy for 6 weeks and will then be randomized to continue pembrolizumab monotherapy or to receive additional intermitted/short-term dabrafenib + trametinib.

Stratification will be baseline LDH level and baseline PD-L1 expression.

Being tested
Pembrolizumab, Dabrafenib, Trametinib, Biopsy, Blood taking
Medical subject headings
Melanoma

What participants receive

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

  • PembrolizumabDrug

  • DabrafenibDrug

  • TrametinibDrug

  • BiopsyProcedure or surgery

    Biopsies will be taken during screening, before randomization, at week 8 (only arm 2-4) after 12 weeks, at week 18 and if PD.

  • Blood takingProcedure or surgery

    Blood will be taken for PBMCs during screening (twice), before randomization, at weeks 12 at week 18 and if PD.

Study groups in NCT02625337
Study groupRoleWhat they receive
Pembrolizumab monoActive comparatorPembrolizumab monotherapy
Receives: Drug: Pembrolizumab; Procedure: Biopsy; Procedure: Blood taking
Pembrolizumab with dabrafenib+trametinib shortExperimentalPembrolizumab combined with a short scheme of dabrafenib+trametinib
Receives: Drug: Pembrolizumab; Drug: Dabrafenib; Drug: Trametinib; Procedure: Biopsy; Procedure: Blood taking
Pembrolizumab with dabrafenib+trametinib intermediateExperimentalPembrolizumab combined with an intermediate scheme of dabrafenib+trametinib
Receives: Drug: Pembrolizumab; Drug: Dabrafenib; Drug: Trametinib; Procedure: Biopsy; Procedure: Blood taking
Pembrolizumab with dabrafenib+trametinib longExperimentalPembrolizumab combined with a long scheme of dabrafenib+trametinib
Receives: Drug: Pembrolizumab; Drug: Dabrafenib; Drug: Trametinib; Procedure: Biopsy; Procedure: Blood taking

What is being measured

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

  1. Safety of different schemes of continuous/intermittent dabrafenib+trametinib during treatment with pembrolizumab as compared to pembrolizumab monotherapy as measured by SUSARs.

    Safety as measured by SUSARs during treatment week 0 till week 18.

    Measured: 18 weeks from baseline

  2. Feasibility of different schemes of continuous/intermittent dabrafenib+trametinib during treatment with pembrolizumab as compared to pembrolizumab monotherapy as measured by adherence to the timelines in the study protocol.

    Feasibility as measured by adherence to the timelines in the study protocol (week 0 till week 18).

    Measured: 18 weeks from baseline.

  3. The immune-activating capacity of different schemes of continuous/intermittent dabrafenib+trametinib during treatment with pembrolizumab as compared to pembrolizumab monotherapy

    Readout will be the alterations in magnitude or breadth of the self-antigen specific T cell responses in the time interval pre-treatment to week 18 intrapatient, and interpatient, pembrolizumab only (cohort 1) versus pembrolizumab plus intermittent dabrafenib/ trametinib (cohorts 2-4). To this purpose, we will analyze melanoma antigen-specific T cells responses by HLA-A2-restricted MHC-tetramer staining.

    Measured: 18 weeks from baseline.

Secondary outcomes (3)

  1. To determine rates of response at week 6, 12, week 18.

    Rates of response at week 6, week 12, week 18 according to RECIST 1.1 criteria

    Measured: Screening, week 6, 12 and 18

  2. To determine progression-free survival starting from randomization.

    Progression-free survival (PFS) starting from randomization to progression using RECIST 1.1 criteria.

    Measured: From randomisation until PD, median 10 months.

  3. Long-term toxicities of intermittent dabrafenib + trametinib during treatment with pembrolizumab as compared to pembrolizumab monotherapy

    Rate and type of late adverse events

    Measured: From beyond week 18, up to 2 years follow-up.

Timeline

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

  1. First posted9 Dec 2015 (estimated)
  2. Study startJan 2016
  3. Primary completionJun 2018 (estimated)
  4. Study completionDec 2018 (estimated)

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 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
32 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02625337
Sponsor's protocol ID
N15IMP
Acronym
IMPemBra
Status last verified
Sep 2017
First submitted
1 Dec 2015
Last updated
15 Sep 2017
Results posted
No
Data monitoring committee
No

Publications

  • Rozeman EA, Versluis JM, Sikorska K, Hoefsmit EP, Dimitriadis P, Rao D, Lacroix R, Grijpink-Ongering LG, Lopez-Yurda M, Heeres BC, van de Wiel BA, Flohil C, Sari A, Heijmink SWTPJ, van den Broek D, Broeks A, de Groot JWB, Vollebergh MA, Wilgenhof S, van Thienen JV, Haanen JBAG, Blank CU. IMPemBra: a phase 2 study comparing pembrolizumab with intermittent/short-term dual MAPK pathway inhibition plus pembrolizumab in patients with melanoma harboring the BRAFV600 mutation. J Immunother Cancer. 2023 Jul;11(7):e006821. doi: 10.1136/jitc-2023-006821.

    PubMed 37479483

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Pembrolizumab, Dabrafenib and Trametinib in people with Metastatic Melanoma, run by The Netherlands Cancer Institute at 1 site in Netherlands.

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 14 inclusion and 15 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: status not confirmed, as of the sponsor's last update on 15 Sep 2017. 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 Netherlands. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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

Are results available for this study?

Results are not available in the source record.

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

Contact Christian U. Blank, Prof. (+31205122570, c.blank@nki.nl), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Safety of different schemes of continuous/intermittent dabrafenib+trametinib during treatment with pembrolizumab as compared to pembrolizumab monotherapy as measured by SUSARs. (time frame: 18 weeks from baseline). The study lists 3 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 NCT02625337, which also lists 1 linked publication.

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 15 Sep 2017.

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