A clinical trial comparing continuous Selumetinib versus continuous or interrupted Selumetinib in combination with weekly Paclitaxel in Metastatic Uveal Melanoma.

Phase 1

• Conditions: Metastatic uveal melanoma; MedDRA version: 21.0Level: PTClassification code 10068117Term: Metastatic ocular melanomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2014-004437-22-GB
• Lead Sponsor: niversity of Liverpool

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2015-07-15
• Last Update Posted: 7 December 2020

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 72

Inclusion Criteria

•Histologically or cytologically confirmed metastatic uveal melanoma.
•Patients must have measurable disease, defined by RECIST 1.1.
•Age =18 years.
•ECOG performance status 0-2.
•Life expectancy of greater than 3 months.
•Able to swallow and retain orally-administered 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.
•All prior treatment-related toxicities must be CTCAE v4 grade = 1 (except alopecia) at the time of randomization.
•Laboratory values as listed below (SI units):
-Total bilirubin = 1.5 X institutional upper limit of normal (ULN).
-Aspartate aminotransferase or alanine aminotransferase >2.5 x ULN (or =5 ULN in presence of liver metastases).
-Haemoglobin =9.0 g/dL.
-Platelets >100x109/L (100,000 per mm3).
-Absolute neutrophil count >1.5x109/L (1500 per mm3).
-Creatinine = 1.5 mg/dL OR calculated creatinine clearance (Cockroft-Gault formula) =50 mL/min OR 24-hour urine creatinine clearance =50 mL/min.
•Female patients of child-bearing potential should have a negative pregnancy test.

Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 0
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 0

Exclusion Criteria

•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 non-chemotherapy locoregional therapy for liver metastases, but who have documented evidence of progression of metastatic disease would however be eligible.
•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 anti-convulsant medications for at least 4 weeks prior to the first dose of study medication.
•Prior exposure to MEK, Ras, or Raf inhibitors or history of hypersensitivity to any excipient agents.
•History of another malignancy unless disease-free for 3 years. Patients, who have had a completely resected non-melanoma skin cancer, are eligible.
•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.
•Symptomatic or untreated leptomeningeal or brain metastases or spinal cord compression. Treated brain metastases must have been stable for at least 1 month.
•Current use of a prohibited medication.
•Cardiac conditions as follows:
-Uncontrolled hypertension (BP =150/95 mmHg despite medical therapy).
-Acute coronary syndrome within 6 months prior to starting treatment.
-Baseline Left ventricular ejection fraction (LVEF) below the LLN or <55% measured by echocardiography or institution’s LLN for MUGA.
-Atrial fibrillation with a ventricular rate >100 bpm on ECG at rest.
-Symptomatic heart failure NYHA Class II-IV, prior or current cardiomyopathy, or severe valvular heart disease (refer to Appendix 1).
-Prior or current cardiomyopathy including but not limited to the following:
- known hypertrophic cardiomyopathy
- known arrhythmogenic right ventricular cardiomyopathy
- previous moderate or severe impairment of left ventricular systolic function (LVEF <45% on echocardiography or equivalent on MuGA) even if full recovery has occurred.
-Uncontrolled angina (Canadian Cardiovascular Society grade II-IV despite medical therapy, refer to Appendix 2).
-Acute coronary syndrome within 6 months prior to starting treatment.
-QTcF >450ms or other factors that increase the risk of QT prolongation.
•Ophthalmological conditions as follows (unless in the eye involved by uveal melanoma):
-Intra-ocular pressure >21 mmHg, or uncontrolled glaucoma (irrespective of intra-ocular pressure).
-Current or past history of retinal pigment epithelial detachment (RPED)/central serous retinopathy(CSR) or retinal vein occlusion.
•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.
•Female patients who are breast-feeding.
•Male or female patients of reproductive potential who are not employing an effective method of contraception.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified