CompletedPhase 1/2

HDAC Inhibitor Vorinostat in Resistant BRAF V600 Mutated Advanced Melanoma

Netherlands33 participantsStarted 2016-06

Plain-language summary

This is a mono-center open-label proof-of-concept pharmacologic study to explore the efficacy and safety of vorinostat in advanced BRAF mutated melanoma, which became resistant for BRAF-inhibitors or the combination of BRAF- and MEK-inhibitors.

Who can participate

SexALL

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Inclusion criteria

✓. Histological proof of advanced melanoma with BRAF V600 mutation;
✓. Progression of disease, according to RECIST 1.1, while on treatment with BRAFi, such as vemurafenib or dabrafenib; or a combination of BRAF - and MEK inhibitors, such as trametinib and dabrafenib;
✓. Previous documented response (partial or complete) for at least 4 weeks to treatment with BRAFi and/or BRAFi+MEKi;
✓. Start with vorinostat treatment within a maximum period of 1 week after discontinuation of BRAFi and/or BRAFi+MEKi.
✓. Age ≥ 18 years;
✓. Able and willing to give written informed consent;
✓. WHO performance status of 0, 1 or 2;
✓. Able and willing to undergo blood sampling for PK and PD analysis;

Exclusion criteria

✕. Any treatment with investigational drugs, except BRAFi and MEKi, within 28 days prior to receiving the first dose of investigational treatment; or 21 days for standard chemotherapy and immunotherapy;
✕. Patients who have had previous treatment with vorinostat or other HDAC inhibitors;
✕. Leptomeningeal disease;
✕. Symptomatic brain metastasis. Patients previously treated or untreated for the condition and/or who are asymptomatic in the absence of corticosteroid therapy are allowed to enroll. Patients are not permitted to receive enzyme inducing anti-epileptic drugs or corticosteroids;
✕. Clinical progression of melanoma in the first week of discontinuation of BRAFi or BRAFi/MEKi;
✕. Woman who are pregnant or breast feeding;
✕. Unreliable contraceptive methods. Both men and women enrolled in this trial must agree to use a reliable contraceptive method from screening until 30 days after the last dose of study medication (adequate contraceptive methods are: oral or injected or implanted hormonal methods of contraception, condom, sterilization, other barrier contraceptive measures preferably in combination with condoms, true abstinence);
✕. Radiotherapy within the last 4 weeks prior to receiving the first dose of investigational treatment; except 1x8 Gray for pain palliation;

What they're measuring

Anti-tumor response rate in at least 30% of the treated patients.

Timeframe: CT scan every 6 weeks up to 24 months and monthly phone call until start of subsequent anticancer therapy or until all patients have been followed up for at least 24 months or have been lost to follow up, whichever occurs first.

Trial details

NCT IDNCT02836548

SponsorThe Netherlands Cancer Institute

Sponsor typeOTHER

Study typeINTERVENTIONAL

Primary completion2023-11

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