Additional identifiers
EudraCT number
2014-004437-22
ClinicalTrials.gov number
Protocol/serial number
19090
Study information
Scientific title
A randomised three arm, open label, phase II study of continuous selumetinib versus continuous or interrupted selumetinib in combination with weekly paclitaxel in metastatic uveal melanoma
Acronym
SelPac
Study hypothesis
This study aims to compare continuous single agent selumetinib to combination paclitaxel and selumetinib in either a continuous or intermittent schedule.
Ethics approval
London - City & East Research Ethics Committee, 08/04/2015, ref: 15/LO/0159
Study design
Randomised; Interventional; Design type: Treatment
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Other
Trial type
Treatment
Patient information sheet
Not available in web format, please use contact details to request a participant information sheet
Condition
Topic: Cancer; Subtopic: Melanoma; Disease: Melanoma
Intervention
1. Paclitaxel, IMP
2. Selumetinib, IMP
Intervention type
Other
Phase
Phase II
Drug names
Primary outcome measure
Progression Free Survival (PFS) time.; Timepoint(s): Progression
Secondary outcome measures
1. GNAQ/GNA11 mutation status
2. RECIST Response
3. Safety and toxicity
Overall trial start date
01/08/2015
Overall trial end date
04/08/2020
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
Histologically or cytologically confirmed metastatic uveal melanoma
1. Patients must have measurable disease, defined by RECIST 1.1
2. Age at least18 years
3. ECOG performance status 02
4. Life expectancy of greater than 3 months
5. Able to swallow and retain orallyadministered medication and does not have any clinically significant gastrointestinal abnormalities that may alter absorption such as malabsorption syndrome or major resection of the stomach or bowels
6. All prior treatmentrelated toxicities must be CTCAE v4 grade = 1 (except alopecia) at the time of randomization
7. Laboratory values as listed below (SI units):
7.1. Total bilirubin = 1.5 X institutional upper limit of normal (ULN)
7.2. Aspartate aminotransferase or alanine aminotransferase >2.5 x ULN (or =5 ULN in presence of liver metastases)
7.3. Haemoglobin =9.0 g/dL
7.4. Platelets >100x109/L (100,000 per mm3)
7.5. Absolute neutrophil count >1.5x109/L (1500 per mm3)
7.6. Creatinine = 1.5 mg/dL OR calculated creatinine clearance (CockroftGault formula) =50 mL/min OR 24hour urine creatinine clearance =50 mL/min
8. Female patients of childbearing potential should have a negative pregnancy test
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
Sample Size: 77 evaluable patients will be randomised to arms A, B and C across 13 UK centres and 1 German centre. Subjects will be randomised 1:1:1 between the 3 arms.
Participant exclusion criteria
1. Patients may not have received prior chemotherapy for uveal melanoma. This includes patients who have received isolated hepatic perfusion of chemotherapy. Patients who have received prior immunotherapy or nonchemotherapy locoregional therapy for liver metastases, but who have documented evidence of progression of metastatic disease would however be eligible
2. Patients who have a known or suspected brain metastases or spinal cord compression, unless asymptomatic, has been treated with surgery and / or radiation, and has been stable without requiring corticosteroids nor anticonvulsant medications for at least 4 weeks prior to the first dose of study medication
3. Prior exposure to MEK, Ras, or Raf inhibitors or history of hypersensitivity to any excipient agents.
4. History of another malignancy unless diseasefree for 3 years. Patients, who have had a completely resected nonmelanoma skin cancer, are eligible
5. Any permitted previous treatment must have been greater than 21 days prior to study treatment starting and all toxicities from previous treatments should have resolved
6. Symptomatic or untreated leptomeningeal or brain metastases or spinal cord compression. Treated brain metastases must have been stable for at least 1 month
7. Current use of a prohibited medication
8. Cardiac conditions as follows:
8.1. Uncontrolled hypertension (BP =150/95 mmHg despite medical therapy)
8.2. Acute coronary syndrome within 6 months prior to starting treatment
8.3. Baseline Left ventricular ejection fraction (LVEF) below the LLN or <55% measured by echocardiography or institution’s LLN for MUGA
8.4. Atrial fibrillation with a ventricular rate >100 bpm on ECG at rest
8.5. Symptomatic heart failure NYHA Class IIIV, prior or current cardiomyopathy, or severe valvular heart disease
8.6. Prior or current cardiomyopathy including but not limited to the following:
8.7. Known hypertrophic cardiomyopathy
8.8. Known arrhythmogenic right ventricular cardiomyopathy
8.9. Previous moderate or severe impairment of left ventricular systolic function (LVEF <45% on echocardiography or equivalent on MuGA) even if full recovery has occurred
8.10.Uncontrolled angina (Canadian Cardiovascular Society grade IIIV despite medical therapy)
8.11. Acute coronary syndrome within 6 months prior to starting treatment
8.12. QTcF >450ms or other factors that increase the risk of QT prolongation
9. Ophthalmological conditions as follows (unless in the eye involved by uveal melanoma):
9.1. Intraocular pressure >21 mmHg, or uncontrolled glaucoma (irrespective of intraocular pressure)
9.2. Current or past history of retinal pigment epithelial detachment (RPED)/central serous retinopathy(CSR) or retinal vein occlusion
10. Uncontrolled intercurrent illness or uncontrolled systemic disease including, but not limited to, ongoing or active infection – including any patient known to have hepatitis B, hepatitis C or human immunodeficiency virus (HIV), symptomatic congestive heart failure, unstable/uncontrolled angina pectoris, uncontrolled cardiac arrhythmia, QTc prolongation, active bleeding diatheses, renal transplant or psychiatric illness/social situations that would limit compliance with study requirements
11. Female patients who are breastfeeding
12. Male or female patients of reproductive potential who are not employing an effective method of contraception
Recruitment start date
01/08/2015
Recruitment end date
28/11/2018
Locations
Countries of recruitment
Germany, United Kingdom
Trial participating centre
Liverpool Clinical Trials Centre
University of Liverpool
1st Floor Block C, Waterhouse Building
3 Brownlow Street
Liverpool
L69 3GL
United Kingdom
Funders
Funder type
Government
Funder name
AstraZeneca
Alternative name(s)
AstraZeneca PLC
Funding Body Type
private sector organisation
Funding Body Subtype
For-profit companies (industry)
Location
United Kingdom
Results and Publications
Publication and dissemination plan
Planned publication in a high-impact peer reviewed journal
IPD sharing statement
The data sharing plans for the current study are unknown and will be made available at a later date
Intention to publish date
04/08/2021
Participant level data
To be made available at a later date
Basic results (scientific)
Publication list