"Dabrafenib and Trametinib in Circulating Free DNA BRAFV600 Mutated Metastatic Melanoma Patients: a Prospective Phase II, Open Label, Multicentre Study - (Bioliquid TAILOR Study - BIOTAILOR)"

  • STATUS
    Recruiting
  • End date
    Feb 1, 2025
  • participants needed
    35
  • sponsor
    Fondazione Melanoma Onlus
Updated on 20 April 2022
metastatic melanoma
measurable disease
BRAF
braf inhibitor
trametinib
immunomodulators
dabrafenib
immunologic adjuvant
cytotoxic t-lymphocyte antigen 4

Summary

There is evidence from cohort studies and metanalysis that a shift from BRAFWT to BRAF mutated melanomas can occur (Colombino JCO 2012, Valchis EJC 2017). Based on previous studies we expect that 15% of tissue BRAF WT patients treated with anti PD-1 will become circulating free DNA BRAF (CfDNA BRAF) mutation-positive and, at progression, they will be elegible to be treated with dabrafenib/trametinib. We aimed to design a clinical phase II trial in order to evaluate the activity of Dabrafenib and Trametinib in patients with Tissue BRAFWT signature and a molecular shift to circulating free DNA BRAF mutated positive melanomas upon progression to anti PD-1 therapy.

Details
Condition Melanoma
Treatment Dabrafenib, Trametinib
Clinical Study IdentifierNCT05299580
SponsorFondazione Melanoma Onlus
Last Modified on20 April 2022

Eligibility

Yes No Not Sure

Inclusion Criteria

Patients of either sex aged ≥ 18 years
Histologically confirmed stage III (unresectable) or stage IV melanoma
Tissue BRAFWT signature and a molecular shift to circulating free DNA BRAF mutated positive melanomas upon progression to anti PD-1 therapy
Tumor biopsy, if feasible, to confirm the BRAFV600 mutation at progression
Previous adjuvant treatment, including checkpoint inhibitors anti CTLA-4, anti PD- 1/PDL-1 is allowed, except for stage IV (if completed at least 6 months prior to enrollment, and all related adverse events have either returned to baseline or stabilized). BRAF inhibitor treatment in adjuvant setting is not permitted
Last previous treatment for metastatic disease MUST BE Anti-PD1 as single agent
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
Measurable disease by computed tomography (CT) or Magnetic Resonance Imaging (MRI) per RECIST 1.1 criteria
Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 to 2 (see Appendix II)
Female subjects of childbearing potential must have a negative pregnancy test result at baseline and must practice two highly effective methods of contraception for the duration of the study, EOT, at 30-day and 150-day safety follow up
Sexually active males must agree to use effective contraception methods throughout treatment and for 150 days after stopping treatment and should not father a child in this period. A condom is required to be used by vasectomized men as well during intercourse in order to prevent delivery of the drug via semen
Adequate baseline organ function
Life expectancy of at least 3 months
Ability to understand study-related patient information and provision of written informed consent for participation in the study

Exclusion Criteria

Symptomatic brain metastases
History of another malignancy, 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) or subjects with a history of completely resected nonmelanoma skin cancer
A history or current evidence/risk of retinal vein occlusion (RVO) or central serous retinopathy including
Presence of predisposing factors to RVO or central serous retinopathy (e.g., uncontrolled glaucoma or ocular hypertension, uncontrolled hypertension, uncontrolled diabetes mellitus, or a history of hyperviscosity or hypercoagulability syndromes); or
Visible retinal pathology as assessed by ophthalmic examination that is considered a risk factor for RVO or central serous retinopathy such as: i. Evidence of new optic disc cupping; ii. Evidence of new visual field defects on automated perimetry; iii. Intraocular pressure >21 mmHg as measured by tonometry
A history of clinically significant or active interstitial lung disease or
pneumonitis
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
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)
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 >480 msec
A history or evidence of current clinically significant uncontrolled arrhythmias; Exception: Subjects with atrial fibrillation controlled for > 30 days prior to enrollment are eligible
A history (within 6 months prior to enrollment) of acute coronary syndromes (including myocardial infarction or unstable angina), coronary angioplasty
A history or evidence of current >= Class II congestive heart failure as defined by the New York Heart Association (NYHA) guidelines
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 or permanent pacemakers
Known cardiac metastases
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
Female subjects who are pregnant (positive pregnancy test), breast-feeding, or who are
of childbearing potential and not practicing a reliable method of birth
control
Inability to regularly access site facilities for logistical or other reasons
History of poor co-operation, non-compliance with medical treatment, or unreliability
Participation in any interventional drug or medical device study within 30 days prior to treatment start
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