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Trial record 40 of 2241 for:    Melanoma

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
Sponsor:
Information provided by (Responsible Party):
Dr Paul Lorigan, The Christie NHS Foundation Trust

Brief Summary:

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)
Primary Purpose: Treatment
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

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Melanoma

Arm Intervention/treatment
Experimental: PLX3397
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.
Drug: PLX3397
PLX3397 capsules 1000mg/day as monotherapy
Other Name: Targeted therapy




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

  4. 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.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients with KIT mutated histologically proven advanced mucosal or acral melanoma in which the mutation is not known to be associated with PLX3397 resistance
  • Unresectable locally advanced or metastatic disease
  • The presence of one or more clinically or radiologically measurable lesions at least 10mm in size
  • ECOG performance status 0, 1 or 2
  • Life expectancy greater than 12 weeks
  • Age 18 or greater
  • Women must be postmenopausal (no menstrual period for a minimum of 1 year) or have a negative serum pregnancy test on entry in the study (even if surgically sterilised). Men and women of childbearing potential must use adequate birth control measures for the duration of the study and should continue such precautions for 3 months after receiving the last dose of study treatment
  • At least 28 days since major surgery and 7 days since skin/tumour biopsy
  • Serum alanine transaminase (ALT) ≤2.5 x upper limit of normal (ULN) or serum aspartate aminotransferase≤2.5 x ULN
  • Total serum bilirubin ≤1.5 x ULN
  • Serum creatinine ≤1.5 x ULN
  • Haemoglobin ≥90 g/L, absolute neutrophil count ≥1.5 x 109/L, platelets ≥100 x 109/L
  • Prothrombin time (PT) ≤1.5 x ULN
  • The ability to swallow and retain oral medication
  • The capacity to understand the patient information sheet and the ability to provide written informed consent
  • Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests and other study procedures

Exclusion Criteria:

  • Intracranial disease, unless there has been radiological evidence of stable intracranial disease > 6 months. In the case of a solitary brain metastasis, evidence of a disease-free interval of at least 3 months post surgery. All patients previously treated for brain metastases must be stable off corticosteroid therapy for at least 28 days
  • Women who are pregnant, nursing, or planning pregnancy within 6 months after the last treatment
  • Men who plan to father a child within 3 months of the last treatment
  • Use of any investigational drug within 30 days prior to screening
  • Significant cardiac disease including patients who have or who are at significant risk of developing prolongation of corrected QT interval (QTc)
  • Severe and/or uncontrolled medical disease
  • Known chronic liver disease
  • Known HIV infection
  • Previous radiotherapy to 25% or more of the bone marrow and/or radiation therapy in the 4 weeks prior to study entry
  • Prior exposure to a KIT inhibitor
  • Patients with KIT mutations that are known to be associated with PLX3397 resistance
  • Use of Chinese or herbal medication
  • Any malabsorption syndrome (i.e. partial gastrectomy, small bowel resection, crohn's disease or ulcerative colitis)

Information from the National Library of Medicine

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


Contacts
Contact: Paul Lorigan, MBChB, FRCP paul.lorigan@christie.nhs.uk
Contact: Azad Aziz, M.Sc azad.aziz@christie.nhs.uk

Locations
United Kingdom
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         
Sponsors and Collaborators
The Christie NHS Foundation Trust
Investigators
Principal Investigator: Paul Lorigan, MBBCH, FRCP The Christie NHS Foundation Trust

Responsible Party: Dr Paul Lorigan, Chief Investigator, The Christie NHS Foundation Trust
ClinicalTrials.gov Identifier: NCT02071940     History of Changes
Other Study ID Numbers: 11_DOG12_56
First Posted: February 26, 2014    Key Record Dates
Last Update Posted: December 10, 2015
Last Verified: December 2015
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: The output of the trial will be published in the peer review journals and scientific conferences

Keywords provided by Dr Paul Lorigan, The Christie NHS Foundation Trust:
Acral Melanoma subtypes
Mucosal Melanoma subtypes

Additional relevant MeSH terms:
Melanoma
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas