Nilotinib in the treatment of c-KIT mutated advanced melanoma

ISRCTN	ISRCTN39058880
DOI	https://doi.org/10.1186/ISRCTN39058880
ClinicalTrials.gov (NCT)	NCT01395121
Clinical Trials Information System (CTIS)	2009-012945-49
Protocol serial number	ICR-CTSU/2009/10020
Sponsor	The Royal Marsden NHS Foundation Trust/The Institute of Cancer Research (ICR) (UK)
Funders	Cancer Research UK (CRUK) (UK) (ref: C28772/A11401), Novartis (UK)

Submission date: 15/05/2009
Registration date: 10/07/2009
Last edited: 27/09/2024

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Cancer

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

https://www.cancerresearchuk.org/about-cancer/find-a-clinical-trial/a-trial-looking-nilotinib-treat-acral-mucosal-melanoma-skin-cancer-spread

Contact information

Dr James Larkin
Scientific

The Royal Marsden Hospital NHS Foundation Trust
Fulham Road
London
SW3 6JJ
United Kingdom

Phone	+44 (0)20 7808 2132
Email	james.larkin@rmh.nhs.uk

Study information

Primary study design	Interventional
Study design	Single-arm phase II clinical trial
Secondary study design	Non randomised study
Study type	Participant information sheet
Scientific title	A phase II trial of nilotinib in the treatment of c-KIT mutated advanced acral and mucosal melanoma (NICAM)
Study acronym	NICAM
Study objectives	The NICAM trial will test the hypothesis that the c-KIT tyrosine kinase inhibitor nilotinib is active in c-KIT mutant advanced acral and mucosal melanoma.
Ethics approval(s)	Oxfordshire C, 20/11/2009, ref: 09/H0606/103
Health condition(s) or problem(s) studied	Advanced acral or mucosal melanoma
Intervention	Nilotinib 400 mg twice daily (bid). Treatment will continue for as long as the patient receives clinical benefit.
Intervention type	Drug
Phase	Phase II
Drug / device / biological / vaccine name(s)	Nilotinib
Primary outcome measure(s)	Proportion of patients progression free at 6 months
Key secondary outcome measure(s)	1. Response rate at 12 weeks 2. Overall survival at 6 months from treatment start 3. Toxicity of treatment at 6 months from treatment start 4. Correlation between c-KIT mutation, gene amplification, overexpression and response to treatment and survival at 6 months from treatment start 5. Changes in circulating tumour cells at 6 months from treatment start
Completion date	09/03/2017

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Sex	All
Target sample size at registration	24
Total final enrolment	29
Key inclusion criteria	1. Patients with c-KIT mutated histologically proven advanced mucosal or acral melanoma in which the mutation is not known to be associated with nilotinib resistance 2. Unresectable locally advanced or metastatic disease 3. The presence of one or more clinically or radiologically measurable lesions at least 10 mm in size 4. Eastern Cooperative Oncology Group (ECOG) performance status 0, 1 or 2 5. Life expectancy greater than 12 weeks 6. At least 28 days since major surgery and 7 days since skin/tumour biopsy 7. The capacity to understand the patient information sheet and the ability to provide written informed consent 8. Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests and other study procedures 9. Aged 18 years or greater, either sex 10. Women must be post-menopausal (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 (e.g. abstinence, oral contraceptives, intrauterine device, barrier method with spermicide, implantable or injectable contraceptives or surgical sterilisation) for the duration of the study and should continue such precautions for 6 months after receiving the last study treatment. 11. Serum alanine transaminase (ALT) less than or equal to 2.5 x upper limit of normal (ULN), total serum bilirubin less than or equal to 1.5 x ULN 12. Serum creatinine less than or equal to 1.5 x ULN 13. Haemoglobin greater than or equal to 9.0 g/dL, absolute neutrophil count greater than or equal to 1.5 x 10^9/L, platelets greater than or equal to 100 x 10^9/L 14. Prothrombin time (PT) less than or equal to 1.5 x ULN
Key exclusion criteria	1. Intracranial disease, unless there has been radiological evidence of stable intracranial disease greater than 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. 2. Women who are pregnant, nursing, or planning to become pregnant during the course of the trial 3. Men who plan to father a child within 6 months of the last treatment 4. Use of any investigational drug within 30 days prior to screening 5. Significant cardiac disease including patients who have or who are at significant risk of developing prolongation of QTc 6. Severe and/or uncontrolled medical disease 7. Known chronic liver disease 8. Known human immunodeficiency virus (HIV) infection 9. Previous radiotherapy to 25% or more of the bone marrow 10. Radiation therapy in the 4 weeks prior to study entry 11. Prior exposure to a tyrosine kinase inhibitor
Date of first enrolment	15/12/2009
Date of final enrolment	04/08/2014

Locations

Countries of recruitment

United Kingdom
England

Study participating centre

The Royal Marsden Hospital NHS Foundation Trust

London
SW3 6JJ
United Kingdom

Results and Publications

Individual participant data (IPD) Intention to share	Yes
IPD sharing plan summary	Available on request
IPD sharing plan	The datasets generated during and/or analysed during the current study are/will be available upon request from nicam-icrctsu@icr.ac.uk.

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Results article		16/02/2024	05/03/2024	Yes	No
Basic results				No	No
HRA research summary			28/06/2023	No	No
Participant information sheet	Participant information sheet	11/11/2025	11/11/2025	No	Yes

Editorial Notes

27/09/2024: Cancer Research UK link added to plain English summary field.
05/04/2024: Publication reference added.
20/05/2019: The total final enrolment was added.
25/04/2019: Added EudraCT link to basic results (scientific).
23/03/2017: The overall trial end date was changed from 25/11/2015 to 09/03/2017.
06/04/2016: The overall trial end date was changed from 31/12/2011 to 25/11/2015.