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

NCT05299580 | Withdrawn Phase 2

• 1 other identifier: BIO-TAILOR
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 16

Brief 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.

Conditions

Melanoma

Outcome Measures

Primary Outcomes (1)

• 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

  From day 1 up to 24 months Every 12 weeks

Secondary Outcomes (4)

• Progression Free Survival (PFS)

  From day 1 up to 24 months Every 12 weeks

• Overall Survival

  from 28 days from baseline up to 24 months

• Safety - NCI CTC-AE (Version 5.0)

  up to 24 months

• QoL

  From day 1 up to 24 months Every 12 weeks

Study Arms (1)

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.

Drug: dabrafenib; Drug: Trametinib

Interventions

dabrafenib DRUG

Dabrafenib 150 mg bid

single arm

Trametinib DRUG

Trametinib 2mg qd

single arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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;

Sponsors & Collaborators

• Fondazione Melanoma Onlus: lead

Study Sites (16)

IRCCS - Istituto Scientifico Romagnolo per la Cura e lo Studio dei Tumori (I.R.S.T) S.r.l.

Meldola, Forlì-Cesena, 47014, Italy

Location

Azienda Ospedaliera Nazionale SS. Antonio e Biagio e C. Arrigo

Alessandria, Italy

Location

National Institute of Cancer

Bari, 70124, Italy

Location

Università degli Studi di Bari Aldo Moro

Bari, Italy

Location

AOU Sant'Orsola-Malpighi

Bologna, Italy

Location

ASST Spedali Civili Brescia

Brescia, Italy

Location

Azienda Sanitaria Ospedaliera S. Croce e Carle

Cuneo, Italy

Location

IRCCS San Martino - IST

Genova, 16132, Italy

Location

Fondazione I.R.C.C.S. Istituto Nazionale dei Tumori

Milan, 20133, Italy

Location

Azienda Ospedaliera Universitaria di Modena

Modena, Italy

Location

Istituto Nazionale per lo Studio e la Cura dei Tumori "Fondazione Giovanni Pascale"

Naples, 80131, Italy

Location

Istituto Oncologico Veneto

Padua, 35128, Italy

Location

Azienda Ospedaliera Universitaria Policlinico Paolo Giaccone

Palermo, Italy

Location

Istituto Nazionale Tumori Regina Elena

Roma, 00144, Italy

Location

Azienda Ospedaliera Universitaria - Città della Salute e della Scienza di Torino

Torino, Italy

Location

Azienda Ospedaliera Universitaria Integrata di Udine

Udine, Italy

Location

MeSH Terms

Conditions

Melanoma

Interventions

dabrafenib; trametinib

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 23, 2022
• First Posted: March 29, 2022
• Study Start: February 18, 2021
• Primary Completion: March 30, 2023
• Study Completion: March 30, 2023
• Last Updated: September 14, 2023

Record last verified: 2023-09

Locations

IT (16)