A Phase II Study of Sunitinib Versus Dacarbazine in the Treatment of Patients With Metastatic Uveal Melanoma

Study Overview
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Brief Summary
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Doctors usually treat uveal melanoma with radiotherapy or surgery. But if this cancer spreads, it is more difficult to treat. Doctors usually treat uveal melanoma that has spread with a chemotherapy called dacarbazine, but they are always looking to find new ways to treat uveal melanoma. This study aims to find out how well Sunitinib works to treat uveal melanoma and to see how long Sunitinib and Dacarbazine can help to prevent the cancer from getting worse.

Detailed Description
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124 eligible patients will be randomised to either Sunitinib or Dacarbazine treatment. Participants will then attend 3-weekly clinic visits and undergo 12-weekly tumour assessment (CT or MRI scan) until disease progression (according to RECIST 1.1) has been identified. At progression, patients may crossover to the other study treatment and continue with 3-weekly clinic visits and 12-weekly imaging until second progression.

Official Title
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A Randomised Phase II Study of Sunitinib Versus Dacarbazine in the Treatment of Patients With Metastatic Uveal Melanoma

Conditions
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Metastatic Uveal Melanoma

Intervention / Treatment
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* Drug: Dacarbazine
* Drug: Sunitinib


Participation Criteria
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Eligibility Criteria
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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 No 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 Life expectancy > 12 weeks ECOG Performance status 0, 1 or 2 At least one measurable target lesion, for further evaluation according to the Response Evaluation Criteria In Solid Tumours - RECIST version 1.1 completed within 28 days of randomisation Aged > 18 years Adequate haematological, renal and liver function as defined below and performed within 14 days of study inclusion: Hb > 10 g/dl, platelets > 100 x109/L, WCC > 3.0 x109/L, ANC > 1.5x109/L, Bili < 1.5 x ULN, Alk phos < 5 x ULN, transaminases < 5 x ULN, Cr < 1.5 x ULN Able to provide 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 Exclusion Criteria: Patients who have: Conjunctival melanoma Received any previous systemic therapy for uveal melanoma Known leptomeningeal or brain metastases 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) Had treatment with potent CYP3A4 inhibitors and inducers within 7 and 12 days respectively, prior to study treatment administration Therapeutic anticoagulation for treatment of DVT/PE. 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, 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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Arm 1: Dacarbazine<br>Patients will receive 1000mg/m2 every 21 days by IV until progression or unacceptable toxicity. | Drug: Dacarbazine<br>* Dacarbazine: Patients will receive 1000mg/m2 every 21 days by IV until progression or unacceptable toxicity.<br>* Other names: DTIC;|
| Experimental: Arm 2: Sunitinib<br>Sunitinib: Patients will take 50mg orally once a day, for 28 days followed by a 14 day break, until progression or unacceptable toxicity. | Drug: Sunitinib<br>* Sunitinib: Patients will take 50mg orally once a day, for 28 days followed by a 14 day break, until progression or unacceptable toxicity<br>* Other names: Sunitinib Malate;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival | 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. | Once all patients have been followed up for at least 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival | Overall survival will be measured from date of randomisation to the date of death from any cause. Patients still alive at the time of the analysis are censored at the date of the most recent follow-up. | Analysis will take place once all patients have been followed up for at least 3 months | 
| Overall Response Rate | Overall response rate is defined as the proportion of complete (CR) or partial responders (PR) as defined by the RECIST version 1.1 | Analysis will take place once all patients have been followed up for at least 3 months | 
| Time to progression on first-line treatment compared to second-line treatment | Time to progression on first-line treatment compared to second-line treatment for patients who receive cross-over therapy. | Analysis will take place once all patients have been followed up for at least 3 months | 
| Overall response rate on first-line treatment compared to overall response rate on second-line treatment for patients who receive cross-over therapy | Overall response rate on first-line treatment compared to overall response rate on second-line treatment for patients who receive cross-over therapy | Analysis will take place once all patients have been followed up for at least 3 months | 
| Assessment of Adverse Events | Adverse Events recorded following randomisation will be classified using NCI CTCAE version 4. | Analysis will take place once all patients have been followed up for at least 3 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Uveal, Melanoma, Metastatic, Sunitinib