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MelanomaPhase 1/2NCT03391050

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

A Phase 1/2 study testing APR-246 and Dabrafenib in people with Melanoma, run by Aprea Therapeutics at 3 sites in Belgium.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Melanoma
What is being tested?
APR-246 and Dabrafenib
Could I receive a placebo?
No, everyone receives an active treatment
How many people
3 participants
Where
3 sitesBelgium
Study dates
18 Jan 2018to 8 Aug 2018
Phase
Phase 1/2
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 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.
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  • 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.

Who cannot join

  • 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.
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  • 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.

Trial locations and contacts

3 sites in 1 country.

Belgium3 sites

  • Institut Jules Bordet

    Brussels, 1000

  • Universitair Ziekenhuis Antwerpen

    Edegem, 2650

  • CHU UCL Namur - site Sainte-Elisabeth

    Namur, 5000

Other trials in Belgium

About this study

Official title: 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

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.

Conditions
Melanoma
Being tested
APR-246, Dabrafenib
Keywords
Melanoma, Malignant melanoma, Skin cancer, Resistant cancer, Unresectable cancer, Metastatic cancer, BRAF mutant
Medical subject headings
Melanoma, Skin Neoplasms, Neoplasm Metastasis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • APR-246Drug

    Intravenous infusion

  • DabrafenibDrug

    Oral administration

Study groups in NCT03391050
Study groupRoleWhat they receive
APR-246 + DabrafenibExperimentalNot described
Receives: Drug: APR-246; Drug: Dabrafenib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Phase Ib: Adverse Events (AEs)

    Clinical and laboratory adverse events (AEs) and serious adverse events (SAEs) will be reported and graded

    Measured: 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)

  2. Phase Ib: Dose Limiting Toxicities (DLTs)

    Measured: Until end of cycle 1 (cycle length is 28 days)

  3. Phase II: Objective response rate by RECIST1.1

    Measured: Until progression (assessed up to 12 months)

Secondary outcomes (8)

  1. Clinical benefit rate

    Proportion of patients with a CR, PR or Stable Disease (SD) ≥ 4 months

    Measured: Until progression (assessed up to 12 months)

  2. Duration of response

    Measured: Until progression (assessed up to 12 months)

  3. Progression free survival (PFS)

    Measured: Until progression (assessed up to 12 months)

  4. Area under the plasma concentration versus time curve (AUC) for APR-246

    Measured: Until Cycle 1 Day 8 (Phase Ib) or Cycle 1 Day 1 (Phase II)

  5. Plasma drug concentration at a specified time t (Ct) for APR-246

    Measured: Until Cycle 1 Day 8 (Phase Ib) or Cycle 1 Day 1 (Phase II)

  6. Maximum observed plasma concentration (Cmax) of APR-246

    Measured: Until Cycle 1 Day 8 (Phase Ib) or Cycle 1 Day 1 (Phase II)

  7. Time to reach maximum plasma concentration following drug administration (tmax) for APR-246

    Measured: Until Cycle 1 Day 8 (Phase Ib) or Cycle 1 Day 1 (Phase II)

  8. Assessment of metabolic response

    According to classical PERCIST criteria (30%) modified PERCIST criteria (15%) and the consistency classification

    Measured: Until Cycle 2 Day 1 (cycle length is 28 days)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted5 Jan 2018
  2. Study start18 Jan 2018
  3. Primary completion8 Aug 2018
  4. Study completion8 Aug 2018

Why it stopped: Target patient population - difficult to find patientes

Resources

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 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
3 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03391050
Sponsor's protocol ID
APR-633
Status last verified
Jul 2019
First submitted
19 Dec 2017
Last updated
31 Jul 2019
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No

Publications

  • Lehmann S, Bykov VJ, Ali D, Andren O, Cherif H, Tidefelt U, Uggla B, Yachnin J, Juliusson G, Moshfegh A, Paul C, Wiman KG, Andersson PO. Targeting p53 in vivo: a first-in-human study with p53-targeting compound APR-246 in refractory hematologic malignancies and prostate cancer. J Clin Oncol. 2012 Oct 10;30(29):3633-9. doi: 10.1200/JCO.2011.40.7783. Epub 2012 Sep 10.

    PubMed 22965953

  • Deneberg S, Cherif H, Lazarevic V, Andersson PO, von Euler M, Juliusson G, Lehmann S. An open-label phase I dose-finding study of APR-246 in hematological malignancies. Blood Cancer J. 2016 Jul 15;6(7):e447. doi: 10.1038/bcj.2016.60. No abstract available.

    PubMed 27421096

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing APR-246 and Dabrafenib in people with Melanoma, run by Aprea Therapeutics at 3 sites in Belgium.

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 10 inclusion and 13 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: stopped early, as of the sponsor's last update on 31 Jul 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in Belgium. 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 combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

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 stopped early (reason given: Target patient population - difficult to find patientes). Results are not available in the source record.

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?

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)). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03391050, which also lists 2 linked publications.

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 31 Jul 2019.

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