Continuous selumetinib versus continuous or interrupted selumetinib in combination with weekly paclitaxel in metastatic uveal melanoma
| ISRCTN | ISRCTN29621851 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN29621851 |
| EudraCT/CTIS number | 2014-004437-22 |
| Secondary identifying numbers | 19090 |
- Submission date
- 17/06/2015
- Registration date
- 17/06/2015
- Last edited
- 30/01/2024
- 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
Contact information
Miss Louise Handley
Scientific
Scientific
Liverpool Cancer Trials Unit
Cancer Research UK Liverpool Cancer Trials Unit
University of Liverpool
1st floor Block C, Waterhouse Building
3 Brownlow Street
Liverpool
L69 3GL
United Kingdom
Study information
| Study design | Randomised; Interventional; Design type: Treatment |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Other |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use contact details to request a participant information sheet |
| 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 |
| Study acronym | SelPac |
| Study objectives | This study aims to compare continuous single agent selumetinib to combination paclitaxel and selumetinib in either a continuous or intermittent schedule. |
| Ethics approval(s) | London - City & East Research Ethics Committee, 08/04/2015, ref: 15/LO/0159 |
| Health condition(s) or problem(s) studied | Topic: Cancer; Subtopic: Melanoma; Disease: Melanoma |
| Intervention | 1. Paclitaxel, IMP 2. Selumetinib, IMP |
| Intervention type | Other |
| 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 study start date | 01/08/2015 |
| Completion date | 04/08/2020 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | 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. |
| Key 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 |
| Key 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 |
| Date of first enrolment | 01/08/2015 |
| Date of final enrolment | 28/11/2018 |
Locations
Countries of recruitment
- England
- Germany
- United Kingdom
Study participating centre
Liverpool Clinical Trials Centre
University of Liverpool
1st Floor Block C, Waterhouse Building
3 Brownlow Street
Liverpool
L69 3GL
United Kingdom
1st Floor Block C, Waterhouse Building
3 Brownlow Street
Liverpool
L69 3GL
United Kingdom
Sponsor information
University of Liverpool
University/education
University/education
Cancer Research UK Liverpool Cancer Trials Unit
University of Liverpool
1st floor Block C
Waterhouse Building
3 Brownlow Street
Liverpool
L69 3GL
England
United Kingdom
"ROR" |
https://ror.org/04xs57h96 |
|---|
Funders
Funder type
Government
AstraZeneca
Government organisation / For-profit companies (industry)
Government organisation / For-profit companies (industry)
- Alternative name(s)
- AstraZeneca PLC, Pearl Therapeutics
- Location
- United Kingdom
Results and Publications
| Intention to publish date | 04/08/2021 |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Data sharing statement to be made available at a later date |
| Publication and dissemination plan | Planned publication in a high-impact peer reviewed journal |
| IPD sharing plan | The data sharing plans for the current study are unknown and will be made available at a later date |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Basic results | 19/09/2021 | 16/06/2022 | No | No | |
| HRA research summary | 28/06/2023 | No | No | ||
| Protocol file | version 7 | 13/05/2020 | 30/01/2024 | No | No |
Additional files
Editorial Notes
30/01/2024: Protocol file added.
16/06/2022: EU Clinical Trials Register results added.
28/08/2020: The following changes were made to the trial record:
1. The overall trial end date was changed from 01/07/2019 to 04/08/2020.
2. The intention to publish date was changed from 01/07/2020 to 04/08/2021.
3. The target number of participants was changed from 'Planned Sample Size: 123; UK Sample Size: 123; Description: 123 evaluable patients will be randomised to arms A, B and C across 13 UK centres. Subjects will be randomised 1:1:1 between the 3 arms' to '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.'
4. Germany was added to the countries of recruitment.
5. Name of trial participating centre was changed from Liverpool Cancer Trials Unit to Liverpool Clinical Trials Centre.
21/02/2019: Publication and dissemination plan and IPD sharing statement added.
18/02/2019: The following changes were made to the trial record:
1. The recruitment end date was changed from 01/02/2018 to 28/11/2018.
2. The overall trial end date was changed from 01/02/2018 to 01/07/2019.
02/02/2016: Link to lay summary added.
