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A Study of APR-246 in Combination With Dabrafenib in Resistant Patients With BRAF V600 Mutant Melanoma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT03391050
Recruitment Status : Terminated (Target patient population - difficult to find patientes)
First Posted : January 5, 2018
Last Update Posted : July 31, 2019
Jules Bordet Institute
Information provided by (Responsible Party):
Aprea Therapeutics

Tracking Information
First Submitted Date  ICMJE December 19, 2017
First Posted Date  ICMJE January 5, 2018
Last Update Posted Date July 31, 2019
Actual Study Start Date  ICMJE January 18, 2018
Actual Primary Completion Date August 8, 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 3, 2018)
  • Phase Ib: Adverse Events (AEs) [ Time Frame: Up to 30 days after last study treatment day, or at end of study visit due to progression, whichever occurs later (treatment cycles are stopped due to progression, toxicity or patient's decision) ]
    Clinical and laboratory adverse events (AEs) and serious adverse events (SAEs) will be reported and graded
  • Phase Ib: Dose Limiting Toxicities (DLTs) [ Time Frame: Until end of cycle 1 (cycle length is 28 days) ]
  • Phase II: Objective response rate by RECIST1.1 [ Time Frame: Until progression (assessed up to 12 months) ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 3, 2018)
  • Clinical benefit rate [ Time Frame: Until progression (assessed up to 12 months) ]
    Proportion of patients with a CR, PR or Stable Disease (SD) ≥ 4 months
  • Duration of response [ Time Frame: Until progression (assessed up to 12 months) ]
  • Progression free survival (PFS) [ Time Frame: Until progression (assessed up to 12 months) ]
  • Area under the plasma concentration versus time curve (AUC) for APR-246 [ Time Frame: Until Cycle 1 Day 8 (Phase Ib) or Cycle 1 Day 1 (Phase II) ]
  • Plasma drug concentration at a specified time t (Ct) for APR-246 [ Time Frame: Until Cycle 1 Day 8 (Phase Ib) or Cycle 1 Day 1 (Phase II) ]
  • Maximum observed plasma concentration (Cmax) of APR-246 [ Time Frame: Until Cycle 1 Day 8 (Phase Ib) or Cycle 1 Day 1 (Phase II) ]
  • Time to reach maximum plasma concentration following drug administration (tmax) for APR-246 [ Time Frame: Until Cycle 1 Day 8 (Phase Ib) or Cycle 1 Day 1 (Phase II) ]
  • Assessment of metabolic response [ Time Frame: Until Cycle 2 Day 1 (cycle length is 28 days) ]
    According to classical PERCIST criteria (30%) modified PERCIST criteria (15%) and the consistency classification
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
Descriptive Information
Brief Title  ICMJE A Study of APR-246 in Combination With Dabrafenib in Resistant Patients With BRAF V600 Mutant Melanoma
Official Title  ICMJE A Phase Ib/II Study to Investigate the Safety and Clinical Activity of APR-246 in Combination With Dabrafenib in Patients With BRAF V600 Mutant Unresectable and/or mEtastatic Cutaneous MElanoma Resistant to Dabrafenib/Trametinib Combination
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 cutaneous melanoma resistant to the dabrafenib/trametinib combination. In addition, the study aims to assess the safety profile of the combined APR-246 and dabrafenib therapy regimen, to explore potential biomarkers, and to further describe the anti-tumour activity of the combination of APR-246 and dabrafenib. The trial will enroll up to 31 evaluable patients.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Melanoma
Intervention  ICMJE
  • Drug: APR-246
    Intravenous infusion
  • Drug: Dabrafenib
    Oral administration
Study Arms  ICMJE Experimental: APR-246 + Dabrafenib
  • Drug: APR-246
  • Drug: Dabrafenib
Publications *

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: July 29, 2019)
Original Estimated Enrollment  ICMJE
 (submitted: January 3, 2018)
Actual Study Completion Date  ICMJE August 8, 2018
Actual Primary Completion Date August 8, 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • 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 Criteria:

  • 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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Belgium
Removed Location Countries  
Administrative Information
NCT Number  ICMJE NCT03391050
Other Study ID Numbers  ICMJE APR-633
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Aprea Therapeutics
Study Sponsor  ICMJE Aprea Therapeutics
Collaborators  ICMJE Jules Bordet Institute
Investigators  ICMJE
Study Chair: Ahmad Awada, PhD Jules Bordet Institute, Brussels, Belgium
Principal Investigator: Joseph Kerger, MD Jules Bordet Institute, Brussels, Belgium
PRS Account Aprea Therapeutics
Verification Date July 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP