Neoadjuvant intraviTreal ranibizumab treatment in high-risk ocular melanoma patients

ISRCTN	ISRCTN35236442
DOI	https://doi.org/10.1186/ISRCTN35236442
EudraCT/CTIS number	2011-000961-10
Secondary identifying numbers	11316

Submission date: 16/03/2012
Registration date: 16/03/2012
Last edited: 25/10/2022

Recruitment status: Stopped
Overall study status: Stopped
Condition category: Cancer

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Record updated in last year

Plain English summary of protocol

https://www.cancerresearchuk.org/about-cancer/find-a-clinical-trial/a-trial-looking-ranibizumab-eye-cancer-nitro

Contact information

Prof Heinrich Heimann
Scientific

Liverpool University
Liverpool
-
United Kingdom

Email	hheimann@liverpool.ac.uk

Mr Tony Coffey
Public

North West Surgical Trials Centre
Cancer Research UK Liverpool Clinical Trials Unit
Block C
Waterhouse Building
1-3 Brownlow Street
Liverpool
L69 3GL
United Kingdom

Phone	+44 151 794 8929
Email	tony.coffey@liverpool.ac.uk

Study information

Study design	Non-randomised; Interventional; Design type: Treatment
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 contact details to request a participant information sheet
Scientific title	Neoadjuvant IntraviTreal Ranibizumab treatment in high-risk Ocular melanoma patients: a two-stage single-centre phase II single arm study (NITRO trial)
Study acronym	NITRO
Study objectives	NITRO is a two stage phase II non-randomised single centre trial. The trial will recruit patients who require radical treatment (e-nucleation) due to tumour size. Participants will receive 0.5mg in 0.05ml ranibizumab as an intravitreal injection on day 1 of treatment. Tumour assessment will follow 28 days later and one of the following three decisions will be made. 1. If the tumour shows an increase in size, the patient will stop trial treatment and eye removal will be planned. 2. If the assessment shows a reduction in tumour size that may allow for eye sparing treatment (such as endoresection or radiotherapy), the patient will stop trial treatment and appropriate eye sparing treatment will be planned. 3. If a small response or the tumour size has remained stable, the patient may have a further dose of Ranibizumab. Up to 6 doses of trial treatment may be given. All patients will be followed at 6 weeks, 3 months and 6 months following surgery/radiotherapy. Translational samples will be taken at first treatment (day 1) (blood sample, intravitreous fluid sample and tumour biopsy). A second tumour biopsy and intravitreous fluid sample will be taken at final surgery. A second translational blood sample will be taken at the 6 month follow-up. The primary outcome of the trial is to determine the response rate of intravitreal Ranibizumab in high risk Ocular melanoma patients. The secondary outcomes are to explore relationships between ultrasonographic response, serum and intravitreous VEGF levels.
Ethics approval(s)	11/NW/0656; First MREC approval date 07/12/2011
Health condition(s) or problem(s) studied	Topic: National Cancer Research Network; Subtopic: Melanoma; Disease: Melanoma
Intervention	Ranibizumab, Intravitreal injection of 0.5mg in 0.05ml Ranibizumab; Follow Up Length: 6 month(s); Study Entry: Registration only 14 patients will be recruited in the first stage of the trial. The trial will be paused after recruitment and treatment of patient 14. A further 11 patients will be recruited if there are any responders to treatment identified in the first stage.
Intervention type	Drug
Pharmaceutical study type(s)
Phase	Phase II
Drug / device / biological / vaccine name(s)	ranibizumab
Primary outcome measure	Response Rate; Timepoint(s): Response will be measured per patient every 28 days after treatment. Maximum of 6 treatments.
Secondary outcome measures	To explore relationships between ultrasonographic response, serum and intravitreous VEGF levels
Overall study start date	02/04/2012
Completion date	01/08/2013
Reason abandoned (if study stopped)	Participant recruitment issue

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Sex	Both
Target number of participants	Planned Sample Size: 25; UK Sample Size: 25
Total final enrolment	7
Key inclusion criteria	1. Confirmed diagnosis of uveal melanoma requiring enucleation 2. Must have ultrasonographically documented measurable disease within 4 weeks of treatment according to the WHO criteria 3. Prior treatments with chemotherapeutic or antiangiogenic agents for other malignancies are allowed after 6 months of discontinuation 4. Age >=18 years 5. Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 2 6. Platelets ≥100,000mm3 7. White cell count (WCC) ≥ 3.0 x 109/L 8. Absolute neutrophil count (ANC) ≥ 1.0 x 109/L 9. Bilirubin < twice normal, Alkaline Phosphatase < 5 x normal 10. International Normalized Ratio (INR) < 2 11. Cr ≤1.5 ULN 12. Normal blood pressure or controlled hypertension 13. No recent major surgical procedures (laparotomy or thoracotomy) within 4weeks 14. No thromboembolic event within 6 months 15. No known coagulopathy disorder 16. Absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and followup schedule; those conditions should be discussed with the patient before registration in the trial 17. Before patient registration, written informed consent must be given according to ICH/GCP, and national regulations 18. Previous or present vascular intraocular diseases not requiring use of antiangiogenic agents will be allowed 19. Hb ≥ 10g/dl
Key exclusion criteria	1. Serious underlying medical condition according to the judgement of the Principal Investigator 2. Pregnant or nursing patients 3. Inability to provide adequate informed consent 4. Hypersensitivity to the active substance or to any of the excipients 5. Active or suspected ocular or periocular infections 6. Active severe intraocular inflammation
Date of first enrolment	02/04/2012
Date of final enrolment	01/08/2013

Locations

Countries of recruitment

England
United Kingdom

Study participating centre

Liverpool CR-UK Centre - Waterhouse Building

Liverpool
L69 3GL
United Kingdom

Sponsor information

Royal Liverpool and Broadgreen University Hospitals NHS Trust (UK)
Hospital/treatment centre

The Walton Centre for Neurology and Neurosurgery
Prescot Street
Liverpool
L7 8XP
England
United Kingdom

Website	http://www.rlbuht.nhs.uk
"ROR"	https://ror.org/009sa0g06

Funders

Funder type

Charity

Cancer Research UK (CRUK) (UK)
Private sector organisation / Other non-profit organizations

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

Results and Publications

Intention to publish date	31/12/2018
Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
Publication and dissemination plan	To be submitted to an ophthalmology journal in June 2018.
IPD sharing plan	Not provided at time of registration

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Plain English results			07/11/2019	No	Yes
Results article	results	01/02/2020	07/11/2019	Yes	No
HRA research summary			28/06/2023	No	No

Editorial Notes

25/10/2022: Internal review.
07/11/2019: The following changes were made to the trial record:
1. Publication reference added.
2. The total final enrolment was added.
07/06/2018: The following changes have been made:
1. The trial status and recruitment status have been changed to 'stopped'.
2. A publication and dissemination plan has been added.
3. An intention to publish date has been added.
4. Basic results have been added.
5. Tony Coffey has been added as a public contact and Lucy Delaney has been replaced as scientific contact by Prof Heinrich Heimann.
23/05/2016: No publications found, verifying study status with principal investigator.