A Phase II Trial of PLX3397 in the Treatment of Tyrosine Kinase Receptor (KIT) Mutated Advanced Acral and Mucosal Melanoma (PIANO trial)

Phase 1

• Conditions: In a subset of patients with advanced acral and mucosal melanoma exhibiting Tyrosine Kinase Receptor gene(c-KIT) mutation.; MedDRA version: 19.0Level: LLTClassification code 10027152Term: Melanoma of skin (malignant)System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 19.0Level: PTClassification code 10025654Term: Malignant melanoma of sites other than skinSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 19.0Level: LLTClassification code 10000589Term: Acral lentiginous melanoma stage unspecifiedSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 19.0Level: LLTClassification code 10053571Term: MelanomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 19.0Level: LLTClassification code 10025667Term: Malignant melanoma site/stage unspecifiedSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 19.0Level: PTClassification code 10000583Term: Acral lentiginous melanomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 19.0Level: LLTClassification code 10027150Term: Melanoma malignantSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 19.0Level: PTClassification code 10027480Term: Metastatic malignant melanomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2013-002073-22-GB
• Lead Sponsor: The Christie NHS Foundation Trust, R&D

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2015-06-01
• Last Update Posted: 13 June 2016

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 24

Inclusion Criteria

1.Male and female patients = 18 years of age with histologically confirmed KIT mutated advanced mucosal or acral melanoma (exons 9, 11, 13 and 17 will be sequenced. For exon 17 only Asp816 (also know as D816X) mutations are excluded- other exon 17 mutations are allowed)
2.Patients with advanced acral and mucosal melanoma in whom KIT mutations have been confirmed and the mutations are not known to be associated with resistance to PLX3397
3.Patients must have clinically or radiologically measurable lesion of at least 15mm in size
4.Unresectable locally advanced or metastatic disease
5.The capacity to understand the patient information sheet and the ability to provide signed and dated written informed consent prior to any study related procedures
6.Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests and other study procedures
7.ECOG performance status of 0-2
8.Life expectancy greater than 12 weeks
9.Serum alanine aminotransaminase (ALT) =2.5 x upper limit of normal (ULN) or serum aspartate aminotransferase (AST) =2.5 x ULN
10.Total serum bilirubin =1.5 x ULN
11.Serum creatinine =1.5 x ULN
12.Haemoglobin =90 g/L, absolute neutrophil count =1.5 x 109/L, platelets =100 x 109/L
13.Prothrombin time (PT) =1.5 x ULN
14.Men and women of childbearing potential must use adequate birth control measures (e.g. abstinence, oral contraceptives, intrauterine device, barrier method with spermicide, implantable or injectable contraceptives or surgical sterilization). Women must be either postmenopausal (no menstrual period for a minimum of 1 year) or have a negative urine or serum pregnancy test on entry in the study (even if surgically sterilised).
15.At least 28 days since major surgery and 7 days since skin/tumour biopsy
16.The ability to swallow and retain oral medication
17.Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests and other study procedures

Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 18
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 6

Exclusion Criteria

1.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 and off corticosteroid therapy for at least 28 days
2.Women who are pregnant, nursing, or planning pregnancy within 3 months after the last treatment
3.Men who plan to father a child within 3 months of the last dose of treatment
4.Significant cardiac disease including patients who have or who are at significant risk of developing prolongation of QTc
5.Severe and/or uncontrolled medical disease
6.Known chronic liver disease
7.Known HIV infection
8.Previous radiotherapy to 25% or more of the bone marrow and/or radiation therapy in the 4 weeks (28 days) prior to study entry
9.Prior exposure to a KIT inhibitor
10.Patients with KIT mutations that are known to be associated with PLX3397 resistance
11.Current use of Chinese or herbal medication
12.Any malabsorption syndrome (.e. partial gastrectomy, small bowel resection, Crohn’s disease or ulcerative colitis)
13.Use of any investigational drug within 28 days prior to screening or patients who are involved in current research or have recently been involved in any research or clinical trials are excluded.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified