PLX3397 KIT in Acral aNd mucOsal Melanoma

NCT02071940 | Completed Phase 2 DMC

• 1 other identifier: 11_DOG12_56
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 8

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.

Conditions

Malignant Melanoma

Keywords

Acral Melanoma subtypes; Mucosal Melanoma subtypes

Outcome Measures

Primary Outcomes (1)

• Efficacy of PLX3397

  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.

  6 months

Secondary Outcomes (4)

• Response rate

  12 weeks

• Overall Survival

  Participants are followed up for upto an average of 5 years or until the last patient dies, whichever comes first.

• Safety of PLX3397

  minimum of 12 month following stoppage of treatment and for minimum of 5 years for patients remaining on treatment

• Mechanism of response and resistance to PLX3397

  For 12 weeks or until the patient stops treatment

Study Arms (1)

PLX3397

EXPERIMENTAL

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

Interventions

PLX3397 DRUG

PLX3397 capsules 1000mg/day as monotherapy

Also known as: Targeted therapy

PLX3397

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• The Christie NHS Foundation Trust: lead
• Cancer Research UK: collaborator
• Christie Charitable Funds: collaborator

Study Sites (8)

The Christie NHS Foundation Trust

Manchester, Greater Manchester, M20 4BX, United Kingdom

Location

The Beatson West of Scotland Cancer Centre

Glasgow, Scotland, G12 OXH, United Kingdom

Location

Abertawe Bro Morgannwg University Health Board, Singleton Hospital

Swansea, Wales, SA2 8QA, United Kingdom

Location

St James' University Hospital

Leeds, Yorkshire, LS9 7TF, United Kingdom

Location

Cancer Clinical Trials Centre- Weston Park Hospital

Sheffield, Yorkshire, S10 2SJ, United Kingdom

Location

Cambridge University Hospitals NHS FT - Addenbrookes Hospital

Cambridge, CB2 0QQ, United Kingdom

Location

The Royal Marsden NHS Foundation Trust

London, SW3 6JJ, United Kingdom

Location

Oxford University Hospitals NHS Trust- Churchill Hospital

Oxford, OX3 7LE, United Kingdom

Location

MeSH Terms

Conditions

Melanoma

Interventions

pexidartinib

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Paul Lorigan, MBBCH, FRCP

  The Christie NHS Foundation Trust

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 8, 2013
• First Posted: February 26, 2014
• Study Start: October 1, 2015
• Primary Completion: March 2, 2021
• Study Completion: March 2, 2021
• Last Updated: August 12, 2021

Record last verified: 2021-08

Data Sharing

• IPD Sharing: Will not share

Locations

GB (8)