PLX3397 KIT in Acral aNd mucOsal Melanoma

• Status: Completed
• Trial end date: 2021-03-02
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: The Christie NHS Foundation Trust
• Collaborators: Cancer Research UK; Christie Charitable Funds

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)