Condition category
Cancer
Date applied
16/03/2012
Date assigned
16/03/2012
Last edited
07/06/2018
Prospective/Retrospective
Prospectively registered
Overall trial status
Stopped
Recruitment status
Stopped

Contact information

Type

Scientific

Primary contact

Prof Heinrich Heimann

ORCID ID

Contact details

Liverpool University
Liverpool
-
United Kingdom
-
hheimann@liverpool.ac.uk

Type

Public

Additional contact

Mr Tony Coffey

ORCID ID

Contact details

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

Additional identifiers

EudraCT number

2011-000961-10

ClinicalTrials.gov number

Protocol/serial number

11316

Study information

Scientific title

Neoadjuvant IntraviTreal Ranibizumab treatment in high-risk Ocular melanoma patients: a two-stage single-centre phase II single arm study (NITRO trial)

Acronym

NITRO

Study hypothesis

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

11/NW/0656; First MREC approval date 07/12/2011

Study design

Non-randomised; Interventional; Design type: Treatment

Primary study design

Interventional

Secondary study design

Non randomised study

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, please use contact details to request a participant information sheet

Condition

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

Phase

Phase II

Drug names

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 trial start date

02/04/2012

Overall trial end date

01/08/2013

Reason abandoned (if study stopped)

Participant recruitment issue

Eligibility

Participant 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

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

Planned Sample Size: 25; UK Sample Size: 25

Participant 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

Recruitment start date

02/04/2012

Recruitment end date

01/08/2013

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Liverpool CR-UK Centre - Waterhouse Building
Liverpool
L69 3GL
United Kingdom

Sponsor information

Organisation

Royal Liverpool and Broadgreen University Hospitals NHS Trust (UK)

Sponsor details

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

Sponsor type

Hospital/treatment centre

Website

http://www.rlbuht.nhs.uk

Funders

Funder type

Charity

Funder name

Cancer Research UK (CRUK) (UK)

Alternative name(s)

CRUK

Funding Body Type

private sector organisation

Funding Body Subtype

other non-profit

Location

United Kingdom

Results and Publications

Publication and dissemination plan

To be submitted to an ophthalmology journal in June 2018.

Intention to publish date

31/12/2018

Participant level data

Not provided at time of registration

Basic results (scientific)

A total of 7 patients were recruited to the study, with a median age of 66 years. There were 5 males and 2 females . Duration of symptoms was 6 months (mean, range 3-9 months). At baseline, the longest basal diameter was 15.1 mm (mean, range 10-20.4 mm) with a height measured by ultrasonography of 8.6 mm (mean, range 4-12.7mm). Exudative retinal detachment was present in one patient. Visual acuity was 87 letters (ETDRS) (mean, range 104 letters-counting fingers).
No patients achieved complete or partial response at any visit. The study was therefore abandoned and no further patients were recruited. 0/7 patients completed the 6 injections, all withdrew early due to either patient choice or objective progression judged clinically. The last tumour dimensions prior to enucleation were longest basal diameter 15.6 mm (mean, range 12.2-19.9 mm) and height 9.2 mm (mean, range 4.6-12.5).
All patients subsequently underwent enucleation with no complications. Histopathological analysis revealed mixed cell melanoma in 5/7 (71%) and spindle cell morphology in 2/7 (29%) with ciliary body involvement in 4/7 (57%) and the presence of closed loops also in 4/7 (57%). Genetic analysis demonstrated loss of chromosome 3 in 5/7 (71%) but abnormalities in chromosome 1,6 or 8 in all cases.

Publication list

Publication citations

Additional files

Editorial Notes

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.