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Malignant MelanomaPhase 2NCT02296996

Dabrafenib and Trametinib for BRAF-inhibitor Pretreated Patients

A Phase 2 study testing Dabrafenib + Trametinib in people with Malignant Melanoma, run by Universitair Ziekenhuis Brussel at 1 site in Belgium.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

Patients with BRAF V600 mutant advanced melanoma benefit from treatment with a BRAF-inhibitor (e.g. dabrafenib, vemurafenib) and from combination of a BRAF- and MEK-inhibitor (e.g. dabrafenib and trametinib). Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Malignant Melanoma
What is being tested?
Dabrafenib + Trametinib
Could I receive a placebo?
No, everyone receives an active treatment
How many people
25 participants
Where
1 siteBelgium
Study dates
Oct 2014to Dec 2017
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

  • 18 years of age and signed written informed consent.
  • Histologically confirmed cutaneous melanoma that is either Stage IIIC (unresectable) or Stage IV (metastatic), and determined to be BRAF V600E/K mutation-positive.
  • Subjects must have failed at least two prior systemic anti-cancer treatments for Stage IIIC (unresectable) or Stage IV (metastatic) melanoma that must have included:
  • Treatment with a BRAF inhibitor (including but not limited to dabrafenib, vemurafenib, and LGX818) and progression of disease per RECIST, version 1.1 [Eisenhauer, 2009] must have been documented during this treatment.
  • Treatment with ipilimumab (or an alternative experimental immunotherapy) and progression of disease per immune related response criteria [Wolchock Clin Cancer Res December 1, 2009 15; 7412] must have been documented during this treatment.
  • Documented progression of disease per RECIST, version 1.1 [Eisenhauer, 2009]) or per immune related response criteria [Wolchock Clin Cancer Res December 1, 2009 15; 7412] if the latest systemic therapy administered was ipilimumab, an anti-PD1 or anti-PD-L1 therapy, or any other experimental immunotherapy.
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  • The presence of at least one measurable lesion per RECIST, version 1.1 [Eisenhauer, 2009]).
  • Interval between the date of the last administration of prior therapy for melanoma and the date of recruitment:
  • > 12 weeks following the date of the last administration of a BRAF-inhibitor;
  • > 12 weeks following the date of the first administration and > 4 weeks following the date of the last administration of ipilimumab, or an anti-PD1, or anti-PD-L1 therapy;
  • > 4 weeks following the date of the last administration of chemotherapy (> 6 weeks in case of a nitrosurea or mitomycin C containing regimen);
  • > 4 weeks following major surgery or extensive radiotherapy.
  • Subjects with ocular melanoma are not eligible.
  • All prior anti-cancer treatment-related toxicities (except alopecia and laboratory values as listed on Table 2) must be ≤ Grade 1 according to the Common Terminology Criteria for Adverse Events version 4 (CTCAE version 4.0; National Cancer Institute ( NCI,) 2009) at the time of recruitment.
  • Able to swallow and retain oral medication and must not have any clinically significant gastrointestinal abnormalities that may alter absorption such as malabsorption syndrome or major resection of the stomach or bowels.
  • Women of childbearing potential must have a negative serum pregnancy test within 7 days prior to recruitment and agree to use effective contraception, as defined in Section 7.3.3.1, throughout the treatment period, and for 4 months after the last dose of study treatment.
  • An Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2 [Oken, 1982]. Refer to Appendix 1 for details.
  • Adequate baseline organ function as defined in Table 2.

Who cannot join

  • Grade 4 or repetitive grade 3 adverse event(s) related to prior treatment with a BRAF- and/or MEK inhibitor.
  • Any contra-indication for evaluation by whole body CT and MRI of the brain.
  • Taken an investigational drug within 28 days or 5 half-lives (minimum 14 days), whichever is shorter, prior to recruitment.
  • Current use of a prohibited medication as described in Section 6 or requires any of these medications during treatment.
  • History of another malignancy, including any malignancy with confirmed activating RAS mutation. Note: Prospective RAS testing is not required. However, if the results of previous RAS testing are known, they must be used in assessing eligibility. Exception: Subjects who have been disease-free for 3 years, (i.e. subjects with second malignancies that are indolent or definitively treated at least 3 years ago) not including malignancy with confirmed activating RAS mutation, or subjects with a history of completely resected non-melanoma skin cancer.
  • Any serious or unstable pre-existing medical conditions (aside from malignancy exceptions specified above), psychiatric disorders, or other conditions that could interfere with the subject's safety, obtaining informed consent, or compliance with study procedures.
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  • Known Human Immunodeficiency Virus (HIV), Hepatitis B Virus (HBV), or Hepatitis C Virus (HCV) infection (subjects with laboratory evidence of cleared HBV and HCV infection will be permitted).
  • Patients with progressive symptoms from active brain metastasis or in need of an increase in corticosteroids dose to control symptoms within 4 weeks prior to recruitment are excluded
  • No enzyme inducing anticonvulsants for ≥ 4 weeks prior to recruitment
  • A history or evidence of cardiovascular risk including any of the following:
  • Current LVEF < LLN
  • A QT interval corrected for heart rate using the Bazett's formula (QTcB; Section 5.6.3.3) ≥480 msec;
  • A history or evidence of current clinically significant uncontrolled arrhythmias; Exception: Subjects with atrial fibrillation controlled for > 30 days prior to recruitment are eligible.
  • A history (within 6 months prior to recruitment) of acute coronary syndromes (including myocardial infarction or unstable angina), coronary angioplasty or stenting;
  • A history or evidence of current ≥Class II congestive heart failure as defined by the New York Heart Association (NYHA) guidelines (Appendix 4);
  • Treatment refractory hypertension defined as a blood pressure of systolic >140 mmHg and/or diastolic > 90 mm Hg which cannot be controlled by antihypertensive therapy;
  • Patients with intra-cardiac defibrillators;
  • Abnormal cardiac valve morphology (≥grade 2) documented by echocardiogram (subjects with grade 1 abnormalities [i.e., mild regurgitation/stenosis] can be entered on study). Subjects with moderate valvular thickening should not be entered on study.
  • Uncorrectable electrolyte abnormalities (e.g. hypokalaemia, hypomagnesaemia, hypocalcaemia), long QT syndrome or taking medicinal products known to prolong the QT interval.
  • Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to the study treatments, their excipients, and/or dimethyl sulfoxide (DMSO).
  • Females who are pregnant or nursing.
  • Interstitial lung disease or pneumonitis
  • Patients with a prior history of central serous retinopathy or retinal vein occlusion are excluded. Patients with a preexisting major ocular pathology are not eligible.

Trial locations and contacts

1 site in 1 country.

Belgium1 site

  • UZ Brussel

    Brussels, 1090

Other trials in Belgium

About this study

Official title: A Phase II Clinical Trial on the Combination of Dabrafenib and Trametinib for BRAF-inhibitor Pretreated Patients With Advanced BRAF V600 Mutant Melanoma

Patients with BRAF V600 mutant advanced melanoma benefit from treatment with a BRAF-inhibitor (e.g. dabrafenib, vemurafenib) and from combination of a BRAF- and MEK-inhibitor (e.g. dabrafenib and trametinib). Following initial tumor regression, progression is diagnosed in a majority of patients treated with BRAF-inhibitor mono-therapy within the first 12-months of therapy. Various molecular mechanisms that underlie the development of resistance to treatment with a BRAF-inhibitor have been reported. These mechanisms do not include secondary mutations in the BRAF-gene and therefore resistance to BRAF-inhibition could potentially be reversible when selective pressure by BRAF-inhibition is withheld for a sufficient period of time of melanoma progression. This clinical trial protocol addresses the potential renewed anti-tumor activity of combined BRAF- and MEK inhibition with the combination of dabrafenib and trametinib in patients with unresectable AJCC stage III or - IV BRAF V600 mutant melanoma who are documented with progression of disease at least 12 weeks following the last day of dosing of a BRAFinhibitor containing treatment regimen.

Being tested
Dabrafenib + Trametinib
Keywords
BRAF V600, Rechallenge, Combination, Dabrafenib, Trametinib
Medical subject headings
Melanoma

What participants receive

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

  • Dabrafenib + TrametinibDrug

Study groups in NCT02296996
Study groupRoleWhat they receive
Dabrafenib + trametinibExperimentalSingle arm study with dabrafenib + trametinib combination therapy
Receives: Drug: Dabrafenib + Trametinib

What is being measured

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

  1. Overall response rate

    Measured: Participants will be monitored until progression, with an expected average of 6 months

Secondary outcomes (3)

  1. Progression-free survival

    Measured: Participants will be monitored until progression, with an expected average of 6 months

  2. Overall Survival

    Measured: 2 years

  3. Number of Participants with Adverse Events as a Measure of Safety and Tolerability

    Detect adverse events

    Measured: Participants will be monitored until progression, with an expected average of 6 months

Timeline

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

  1. First posted21 Nov 2014 (estimated)
  2. Study startOct 2014
  3. Primary completionDec 2017
  4. Study completionDec 2017

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
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
25 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02296996
Sponsor's protocol ID
UZB-BN- 2013-001
Status last verified
Jan 2019
First submitted
15 Oct 2014
Last updated
23 Jan 2019
Results posted
No
Data monitoring committee
No

Publications

  • Schreuer M, Jansen Y, Planken S, Chevolet I, Seremet T, Kruse V, Neyns B. Combination of dabrafenib plus trametinib for BRAF and MEK inhibitor pretreated patients with advanced BRAFV600-mutant melanoma: an open-label, single arm, dual-centre, phase 2 clinical trial. Lancet Oncol. 2017 Apr;18(4):464-472. doi: 10.1016/S1470-2045(17)30171-7. Epub 2017 Mar 4.

    PubMed 28268064

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Dabrafenib + Trametinib in people with Malignant Melanoma, run by Universitair Ziekenhuis Brussel at 1 site in Belgium.

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 18 inclusion and 23 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: finished, as of the sponsor's last update on 23 Jan 2019. 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 Belgium. 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?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

Overall response rate (time frame: Participants will be monitored until progression, with an expected average of 6 months). 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 NCT02296996, 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 23 Jan 2019.

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