PLX3397 KIT in Acral aNd mucOsal Melanoma (PIANO)
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|ClinicalTrials.gov Identifier: NCT02071940|
Recruitment Status : Recruiting
First Posted : February 26, 2014
Last Update Posted : December 10, 2015
KIT (receptor tyrosine kinase) mutations occur in 15% of acral and mucosal melanomas. PIANO is a single arm, phase II, open-label, multicentre study to evaluate the efficacy and safety (plus molecular basis of such effects) of the KIT inhibitor PLX3397 (developed by Plexxikon) in advanced KIT mutated acral and mucosal melanoma.
In this trial a total of 24 patients (9 in the first stage and 15 in the second stage) will receive treatment over a 24 month recruitment period.
Following consent and successful screening, patients will receive PLX3397 capsules 1000mg/day as monotherapy, and will remain on therapy as long as they are deriving clinical benefit. Patients will be seen every 4 weeks during treatment to monitor response and toxicity. Routine blood tests will be carried out at all visits and pharmacokinetics/pharmacodynamics sampling (1 x 8 milliliter(ml) whole blood sample) will be done pre-dose on Day 1 and Day 15, frozen and stored locally and sent to Plexxikon's vendor for central analysis at the end of the study. Imaging will be carried out every 12 weeks to monitor response. The first 9 patients will also receive two [18F]-fluorodeoxyglucose (FDG) PET scans (baseline and at Day 15).
From specific named participating sites, 12 patients will provide additional (optional) consent to take part in translational research. 5 of these patients will have a fresh tumour biopsy taken at baseline, at day 15 and upon disease progression. The same 5 patients plus an additional 7 patients (to give a total of 12 patients) will also donate blood samples at baseline, 2 weeks, 12 weeks and on disease progression for the evaluation of circulating tumour cells and circulating free tumour DNA.
All patients will be followed up every 6 months until death or for 12 months after the last patient has discontinued study treatment.
|Condition or disease||Intervention/treatment||Phase|
|Malignant Melanoma||Drug: PLX3397||Phase 2|
Show Detailed Description
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||24 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase II Trial of PLX3397 in the Treatment of KIT Mutated Advanced Acral and Mucosal Melanoma|
|Study Start Date :||October 2015|
|Estimated Primary Completion Date :||October 2017|
|Estimated Study Completion Date :||October 2019|
Patients will be given PLX3397 1000mg/day as monotherapy. Patients will remain on treatment as long as they are deriving benefit. This is a single cohort study and so there is no comparator arm - all patients receive the same treatment.
PLX3397 capsules 1000mg/day as monotherapy
Other Name: Targeted therapy
- Efficacy of PLX3397 [ Time Frame: 6 months ]The primary objective of this study is to evaluate the efficacy of PLX3397 in KIT mutated advanced mucosal and acral melanoma as measured by the proportion of study participants tumour progression free at 6 months.
- Response rate [ Time Frame: 12 weeks ]Patient's response rate is measured every 12 weeks (measured by CT scan) until confirmation of tumour progression or death and for a minimum period of 5 years in surviving patients.
- Overall Survival [ Time Frame: Participants are followed up for upto an average of 5 years or until the last patient dies, whichever comes first. ]Overall survival of patients is measured for a minimum of 5 years or until death, which ever comes first or 12 months after the last patient has progressed and finished treatment.
- Safety of PLX3397 [ Time Frame: minimum of 12 month following stoppage of treatment and for minimum of 5 years for patients remaining on treatment ]Safety of PLX3397 will be measured for a minimum of 12 months if patient discontinue treatment or diagnosed with disease progression and stop taking PLX3397 or for a minimum of 5 years in surviving patients receiving treatment. . Patients will be assessed for side effects at each clinic visit and all serious adverse events (SAEs)/ suspected unexpected serious adverse reaction (SUSARs) will be reported in accordance with applicable regulations.
- Mechanism of response and resistance to PLX3397 [ Time Frame: For 12 weeks or until the patient stops treatment ]Blood and tissue samples will be taken at specific timepoints in a subset of patients (additional consent required) to assess the mechanism of response and resistance to PLX3397. Patient samples are taken at baseline, week 2 and week 12 while on treatment or until patients are diagnosed with tumour progression at which point treatment stops.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02071940
|Contact: Paul Lorigan, MBChB, FRCPfirstname.lastname@example.org|
|Contact: Azad Aziz, M.Scemail@example.com|
|The Christie NHS Foundation Trust||Recruiting|
|Manchester, Greater Manchester, United Kingdom, M20 4BX|
|Principal Investigator: Paul Lorigan, MBCBH, FRCP|
|The Royal Marsden NHS Foundation Trust||Not yet recruiting|
|London, United Kingdom, SW3 6JJ|
|Principal Investigator: James Larkin, BMBch, FRCP|
|Principal Investigator:||Paul Lorigan, MBBCH, FRCP||The Christie NHS Foundation Trust|