Status:
TERMINATED
A Study of APR-246 in Combination With Dabrafenib in Resistant Patients With BRAF V600 Mutant Melanoma
Lead Sponsor:
Aprea Therapeutics
Collaborating Sponsors:
Jules Bordet Institute
Conditions:
Melanoma
Eligibility:
All Genders
18+ years
Phase:
PHASE1
PHASE2
Brief Summary
The purpose of this study is to make a preliminary assessment of the efficacy of a combined APR-246 and dabrafenib therapy regimen in patients with BRAFV600 mutant unresectable and/or metastatic cutan...
Eligibility Criteria
Inclusion
- 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.
- 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.
- Measurable disease according to RECIST 1.1 criteria. For phase II only, metabolic measurable disease (according to PERCIST).
- 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.
- ECOG Performance Status of 0 or 1.
- Patients able to swallow and retain oral medication.
- Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.
- 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 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.
- Adequate organ system function.
- Signed informed consent before any study specific procedure and/or treatment happens.
Exclusion
- Presence of uveal melanoma and/or other non-cutaneous melanomas.
- Current use of a prohibited medication or need for any of these medications during treatment with study drug and within 28 days before the first administration of APR-246. I.e., no anti-cancer other than that given in this clinical trial, no immunotherapy, no hormonal cancer therapy, no radiation therapy (except palliative) and no experimental medications are permitted during the trial. All alternative therapies must first be approved by the sponsor. Supportive care therapies are allowed.
- Unresolved toxicity greater than NCI-CTCAE(v4) Grade 1 from previous anti-cancer therapy except alopecia.
- Presence of active gastrointestinal disease or other condition that will interfere significantly with the absorption, distribution, metabolism, or excretion of drugs.
- Known HIV, active hepatitis B or hepatitis C infection.
- Primary malignancy of the central nervous system.
- 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).
- 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.
- History of acute coronary syndromes (including unstable angina), coronary angioplasty, or stenting, or thrombo-embolic event within the past 24 weeks from signature of ICF.
- Class II, III, or IV heart failure as defined by the New York Heart Association (NYHA) functional classification system.
- Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to the study drugs, or excipients.
- Uncontrolled diabetes, hypertension or other medical conditions that may interfere with assessment of toxicity.
- Pregnant or lactating woman.
Key Trial Info
Start Date :
January 18 2018
Trial Type :
INTERVENTIONAL
Allocation :
ACTUAL
End Date :
August 8 2018
Estimated Enrollment :
3 Patients enrolled
Trial Details
Trial ID
NCT03391050
Start Date
January 18 2018
End Date
August 8 2018
Last Update
July 31 2019
Active Locations (3)
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1
Institut Jules Bordet
Brussels, Belgium, 1000
2
Universitair Ziekenhuis Antwerpen
Edegem, Belgium, 2650
3
CHU UCL Namur - site Sainte-Elisabeth
Namur, Belgium, 5000