Nilotinib in the treatment of c-KIT mutated advanced melanoma

ISRCTN	ISRCTN39058880
DOI	https://doi.org/10.1186/ISRCTN39058880
EudraCT/CTIS number	2009-012945-49
ClinicalTrials.gov number	NCT01395121
Secondary identifying numbers	ICR-CTSU/2009/10020

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

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

Study design	Single-arm phase II clinical trial
Primary study design	Interventional
Secondary study design	Non randomised study
Study setting(s)	Hospital
Study type	Treatment
Participant information sheet	Not available in web format, please use the contact details to request a patient 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 hypothesis	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
Condition	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
Pharmaceutical study type(s)
Phase	Phase II
Drug / device / biological / vaccine name(s)	Nilotinib
Primary outcome measure	Proportion of patients progression free at 6 months
Secondary outcome measures	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
Overall study start date	01/08/2009
Overall study end date	09/03/2017

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Sex	Both
Target number of participants	24 (Patients are first registered and progress to study entry if they remain eligible. Approximately 120 patients will be required to register to enable the target of 24 at study entry to be reached).
Total final enrolment	29
Participant 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
Participant 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
Recruitment start date	15/12/2009
Recruitment end date	04/08/2014

Locations

Countries of recruitment

England
United Kingdom

Study participating centre

The Royal Marsden Hospital NHS Foundation Trust

London
SW3 6JJ
United Kingdom

Sponsor information

The Royal Marsden NHS Foundation Trust/The Institute of Cancer Research (ICR) (UK)
Hospital/treatment centre

Clinical R&D Office
West Wing
Downs Road
Sutton
SM2 5PT
England
United Kingdom

Phone	+44 (0)20 8661 3909
Email	research.development@rmh.nhs.uk
Website	http://www.icr.ac.uk/
"ROR"	https://ror.org/0008wzh48

Funders

Funder type

Charity

Cancer Research UK (CRUK) (UK) (ref: C28772/A11401)
Private sector organisation / Other non-profit organizations

Alternative name(s): CR_UK, Cancer Research UK - London, CRUK
Location: United Kingdom

Novartis (UK)
Government organisation / For-profit companies (industry)

Alternative name(s): Novartis AG, Novartis International AG
Location: Switzerland

Results and Publications

Intention to publish date	09/03/2018
Individual participant data (IPD) Intention to share	Yes
IPD sharing plan summary	Available on request
Publication and dissemination plan	A manuscript will be submitted to a quality peer-reviewed journal.
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	Date created	Date added	Peer reviewed?	Patient-facing?
Basic results			No	No
HRA research summary		28/06/2023	No	No
Results article	16/02/2024	05/03/2024	Yes	No

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.