study to investigate the safety and clinical activity of APR-246 in combination with dabrafenib in patients with unresectable metastatic melanoma resistant to dabrafenib /trametinib combinatio
- Conditions
- BRAF V600 Mutant Metastatic MelanomaMedDRA version: 20.0Level: LLTClassification code 10027481Term: Metastatic melanomaSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2017-002577-18-BE
- Lead Sponsor
- APREA THERAPEUTICS AB
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 50
Patients must meet all of the following criteria in order to be eligible for this study:
1.Age = 18 years
2.Patients with confirmed BRAF V600 mutation-positive unresectable and/or metastatic malignant cutaneous melanoma, as determined locally by a validated test and treated with dabrafenib/trametinib first line combination therapy or second line after first line immunotherapy
3.Patients that have progressed according to RECIST 1.1 after at least 4 weeks of treatment with dabrafenib/trametinib and remained on dabrafenib full dose (150mg bid) treatment for the study
4.Measurable disease according to RECIST 1.1 criteria. For phase II only, metabolic measurable disease (according to PERCIST)
5.Availability of tissue from a metastatic lesion. A new biopsy is required unless inaccessible. An archival sample is accepted in that case after discussion with the Sponsor.
6.ECOG Performance Status of 0 or 1
7.Patients able to swallow and retain oral medication
8.Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form
9.For female patients of childbearing potential, a pregnancy test (serum) will be performed within 7 days before inclusion. Woman of childbearing potential must be willing to use one highly effective form of contraception such as described in section 6.3 during anticancer treatment and for at least six months thereafter. Men must agree to use condom during the course of this study and at least six months after the last administration of the study treatment and contraception should be considered for partner of childbearing potential
10.Adequate organ system function
11.Signed informed consent before any study specific procedure and/or treatment happens
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 50
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range
Patients meeting one of the following criteria are not eligible for this study:
1.Presence of Uveal melanoma and/or other non-cutaneous melanomas
2.Current use of a prohibited medication (see section 6.4.2) or need for any of these medications during treatment with study drug and within 28 days before the first administration of APR-246
3.Unresolved toxicity greater than NCI-CTCAE(v4) Grade 1 from previous anti-cancer therapy except alopecia
4.Presence of active gastrointestinal disease or other condition that will interfere significantly with the absorption, distribution, metabolism, or excretion of drugs.
5.Known HIV, active hepatitis B or hepatitis C infection
6.Primary malignancy of the central nervous system
7.History of familial long QT, serious ventricular arrhythmia (no VT > 130 bpm and > 5 extra beats per minute), no QTc = 480 msec calculated from a single ECG reading or a mean of 3 ECG readings using Fridericia’s correction (QTcF = QT/RR0.33) or bradycardia (< 45 bpm)
8.Untreated or symptomatic brain metastasis, leptomeningeal disease or spinal cord compression. Patients who are on a stable dose of corticosteroids > 1 month or off corticosteroids for 2 weeks can be enrolled
9.History of acute coronary syndromes (including unstable angina), coronary angioplasty, stenting or thrombo-embolic event within the past 24 weeks from signature of ICF.
10.Class II, III, or IV heart failure as defined by the New York Heart Association (NYHA) functional classification system.
11.Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to the study drugs, or excipients
12.Uncontrolled diabetes, hypertension or other medical conditions that may interfere with assessment of toxicity
13.Pregnant or lactating woman
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method