E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Metastatic Uveal Melanoma |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10025654 |
E.1.2 | Term | Malignant melanoma of sites other than skin |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Can the progression free survival time of patients with metastatic Uveal Melanoma be extended by treatment with Sunitinib, compared with the treatment by Dacarbazine? |
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E.2.2 | Secondary objectives of the trial |
-What is the overall survival time of the patients participating in the clinical trial? - What is the overall response rate of the patients to their allocated study treatment? -Do either of the treatments cause any adverse events? -How long is time to progression on first-line treatment? -How long is time to progression on second line treatment (for patients who receive cross-over therapy) -What is the overall response rate on first-line treatment compared to overall response rate on second-line treatment (for patients who receive cross-over therapy) -Can certain molecules in the blood help to determine how a patient will do after diagnosis and how they will respond to treatment -How difficult is it to recruit patients with metastatic uveal melanoma to a clinical trial?
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Patients with histologically or cytologically confirmed unresectable, metastatic uveal melanoma (histology must be available from a metastatic site) • Patients with disease that is not amenable to surgery, radiation, or combined modality therapy with curative intent • Patients who have not received any prior systemic therapy for advanced disease, including regional delivery of drug therapy (prior surgery or radiofrequency ablation is acceptable) • Patients who have received prior radiotherapy are eligible, however, measurable lesions must not have been previously irradiated • Patients with a life expectancy > 12 weeks • Patients who have ECOG Performance status 0, 1 or 2 (for ECOG scale of performance (see Appendix B) • Patient has at least one measurable target lesion, for further evaluation according to the Response Evaluation Criteria In Solid Tumours - RECIST version 1.1 (see Appendix C - contrast enhancing lesion with the largest diameter >10mm, based on spiral CT scan or MRI) done within 28 days of randomisation) • Patient is aged > 18 years • Patient has adequate haematological, renal and liver function as defined below and performed within 7 days of randomisation: o Hb > 10 g/dl, platelets > 100x109/L, WCC > 3.0 x109/L, ANC > 1.0x109/L o Bili < 1.5 x ULN, Alk phos < 5 x ULN, AST and ALT < 5 x ULN o Cr < 1.5 x ULN • Patient has provided written informed consent • Females of child-bearing potential who have a negative pregnancy test prior to study entry and be using adequate contraception, which they agree to continue for 12 months after the study treatment
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E.4 | Principal exclusion criteria |
Patients who have: • Conjunctival melanoma • Received any previous systemic therapy for metastatic uveal melanoma • Known leptomeningeal or brain metastases • Had treatment with potent CYP3A4 inhibitors and inducers within 7 and 12 days respectively, prior to study treatment administration • Concomitant treatment with therapeutic doses of anticoagulants (low dose warfarin up to 2mg PO daily for deep vein thrombosis prophylaxis is allowed) • Unstable systemic diseases including uncontrolled hypertension (>150/100 mmHg despite optimal medical therapy) or active uncontrolled infections. • Any of the following within the 6 months prior to study drug administration: myocardial infarction, severe/unstable angina, symptomatic congestive heart failure, cerebrovascular accident or transient ischemic attack, or pulmonary embolism. • Clinically significant abnormal cardiac function with abnormal 12 lead ECG. Ongoing cardiac dysrhythmias of NCI CTCAE grade 2 or greater, poorly controlled atrial fibrillation of any grade, or prolongation of the QTc interval to >450 msec for males or >470 msec for females. • Any other serious or uncontrolled illness which, in the opinion of the investigator, makes it undesirable for the patient to enter the trial • Any medical or psychiatric condition which would influence the ability to provide informed consent • Pregnant or lactating women • Lack of informed consent • Any previous investigational agent within the last 12 weeks • Pregnant or lactating females • Patients who have not provided informed consent • Any medical or psychiatric condition which would influence the ability to provide informed consent • Patients with a history of prior malignant disease (unless they have had more than 3 years free of disease or have had adequately treated non-melanomatous skin cancer or in situ carcinoma of the cervix.
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary outcome measure for this trial is the progression-free survival time measured from date of randomisation.
For patients with evidence of progressive disease (as measured by CT scan, or MRI if necessary) or patients who have died from any cause, progression-free survival time will be calculated to date of progressive disease or date of death (whichever occurs first) and will be counted as events in the analysis. Patients still alive with no evidence of progression at the time of their last visit are censored at the time of the most recent information. Analysis will take place once all patients have been followed up for at least 3 months. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | No |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | Yes |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 12 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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The end of trial is defined as the last follow up visit of the last patient randomised on to the trial. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |