MelanomaPhase 2NCT05299580
"Dabrafenib and Trametinib in Circulating Free DNA BRAFV600 Mutated Metastatic Melanoma Patients: a Prospective Phase II, Open Label, Multicentre Study - (Bioliquid TAILOR Study - BIOTAILOR)"
A Phase 2 study testing dabrafenib and Trametinib in people with Melanoma, run by Fondazione Melanoma Onlus at 16 sites in Italy.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Melanoma
- What is being tested?
- dabrafenib and Trametinib
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 16 sitesItaly
- Study dates
- 18 Feb 2021to 30 Mar 2023
- 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
- 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;
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- 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.
Who cannot join
- 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;
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- 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.
Trial locations and contacts
16 sites in 1 country.
16 sites in 1 country
Italy16 sites
Azienda Ospedaliera Nazionale SS. Antonio e Biagio e C. Arrigo
Alessandria
National Institute of Cancer
Bari, 70124
Università degli Studi di Bari Aldo Moro
Bari
AOU Sant'Orsola-Malpighi
Bologna
ASST Spedali Civili Brescia
Brescia
Azienda Sanitaria Ospedaliera S. Croce e Carle
Cuneo
IRCCS San Martino - IST
Genova, 16132
IRCCS - Istituto Scientifico Romagnolo per la Cura e lo Studio dei Tumori (I.R.S.T) S.r.l.
Meldola, Forlì-Cesena, 47014
Fondazione I.R.C.C.S. Istituto Nazionale dei Tumori
Milan, 20133
Azienda Ospedaliera Universitaria di Modena
Modena
Istituto Nazionale per lo Studio e la Cura dei Tumori "Fondazione Giovanni Pascale"
Naples, 80131
Istituto Oncologico Veneto
Padova, 35128
Azienda Ospedaliera Universitaria Policlinico Paolo Giaccone
Palermo
Istituto Nazionale Tumori Regina Elena
Roma, 00144
Azienda Ospedaliera Universitaria - Città della Salute e della Scienza di Torino
Torino
Azienda Ospedaliera Universitaria Integrata di Udine
Udine
About this study
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.
- Conditions
- Melanoma
- Being tested
- 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.
dabrafenibDrug
Dabrafenib 150 mg bid
TrametinibDrug
Trametinib 2mg qd
| Study group | Role | What they receive |
|---|---|---|
| single arm | Experimental | Patients will be treated with Dabrafenib 150 mg bid and Trametinib 2mg qd. Each cycle is 28 days and the treatment will be continued until documented disease progression, unacceptable toxicity, intercurrent illness that prevents further administration of treatment, investigator's decision to withdraw the subject, subject withdraws consent, pregnancy of the subject, noncompliance with trial treatment or procedure requirements, or administrative reasons. Receives: Drug: dabrafenib; Drug: Trametinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall Response Rate
proportion of patients who have a partial or complete response to therapy; it does not include stable disease and is a direct measure of drug tumoricidal activity
Measured: From day 1 up to 24 months Every 12 weeks
Secondary outcomes (4)
Progression Free Survival (PFS)
the time from the date of first administration of therapy and the date of evidence of progression or death
Measured: From day 1 up to 24 months Every 12 weeks
Overall Survival
the time from the date of first administration of therapy and the date of death from any cause.
Measured: from 28 days from baseline up to 24 months
Safety - NCI CTC-AE (Version 5.0)
Will be used to evaluate the clinical safety of the treatment in this study; patients will be assessed for AEs at each clinical visit and as necessary throughout the study.
Measured: up to 24 months
QoL
the 30-item European Organisation for Research and Treatment of Care quality of life questionnaire
Measured: From day 1 up to 24 months Every 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Mar 2022
- Study start18 Feb 2021
- Primary completion30 Mar 2023
- Study completion30 Mar 2023
Why it stopped: lack of enrollment
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for MelanomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Fondazione Melanoma Onlus
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05299580
- Sponsor's protocol ID
- BIO-TAILOR
- Status last verified
- Sep 2023
- First submitted
- 23 Feb 2022
- Last updated
- 14 Sep 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 14 Sep 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- "Dabrafenib and Trametinib in Circulating Free DNA BRAFV600 Mutated Metastatic Melanoma Patients: a Prospective Phase II, Open Label, Multicentre Study - (Bioliquid TAILOR Study - BIOTAILOR)"
- ClinicalTrials.gov ID
- NCT05299580
- Acronym / sponsor ID
- BIO-TAILOR
- Conditions
- Melanoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: lack of enrollment
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Fondazione Melanoma OnlusUniversity, hospital or other
- Study start
- 18 Feb 2021 (actual)
- Primary completion
- 30 Mar 2023 (actual)
- Study completion
- 30 Mar 2023 (actual)
- First posted
- 29 Mar 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| single arm | Experimental | Drug: dabrafenib, Drug: TrametinibPatients will be treated with Dabrafenib 150 mg bid and Trametinib 2mg qd. Each cycle is 28 days and the treatment will be continued until documented disease progression, unacceptable toxicity, intercurrent illness that prevents further administration of treatment, investigator's decision to withdraw the subject, subject withdraws consent, pregnancy of the subject, noncompliance with trial treatment or procedure requirements, or administrative reasons. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- 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;
Key exclusion criteria (23 listed)
- 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:
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| dabrafenibDabrafenib 150 mg bid | Drug | single arm |
| TrametinibTrametinib 2mg qd | Drug | single arm |
Primary outcome
Overall Response Rate
Time frame: From day 1 up to 24 months Every 12 weeks
proportion of patients who have a partial or complete response to therapy; it does not include stable disease and is a direct measure of drug tumoricidal activity
4 secondary outcomes
Progression Free Survival (PFS)
Time frame: From day 1 up to 24 months Every 12 weeks
Overall Survival
Time frame: from 28 days from baseline up to 24 months
Safety - NCI CTC-AE (Version 5.0)
Time frame: up to 24 months
QoL
Time frame: From day 1 up to 24 months Every 12 weeks
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Sep 2023.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
16 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing dabrafenib and Trametinib in people with Melanoma, run by Fondazione Melanoma Onlus at 16 sites 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 14 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: withdrawn, as of the sponsor's last update on 14 Sep 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 16 sites 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 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 was withdrawn before enrolling participants, so there are no results.
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: From day 1 up to 24 months Every 12 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 14 Sep 2023.