Clinical trial NCT01551459: A Phase II Study of Sunitinib Versus Dacarbazine in the Treatment of Patients With Metastatic Uveal Melanoma
Official title: A Randomised Phase II Study of Sunitinib Versus Dacarbazine in the Treatment of Patients With Metastatic Uveal Melanoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Metastatic Uveal Melanoma
Keywords: Uveal
Melanoma
Metastatic
Sunitinib
Lead sponsor: The Clatterbridge Cancer Centre NHS Foundation Trust
Sponsor class: OTHER
Collaborators: name: Cancer Research UK
name: Pfizer
First posted: 2012-03-12
Enrollment: 124
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Progression Free Survival
timeFrame: Once all patients have been followed up for at least 3 months
Secondary outcomes:
measure: Overall Survival
timeFrame: Analysis will take place once all patients have been followed up for at least 3 months
measure: Overall Response Rate
timeFrame: Analysis will take place once all patients have been followed up for at least 3 months
measure: Time to progression on first-line treatment compared to second-line treatment
timeFrame: Analysis will take place once all patients have been followed up for at least 3 months
measure: Overall response rate on first-line treatment compared to overall response rate on second-line treatment for patients who receive cross-over therapy
timeFrame: Analysis will take place once all patients have been followed up for at least 3 months
measure: Assessment of Adverse Events
timeFrame: Analysis will take place once all patients have been followed up for at least 3 months
Other outcomes:
Locations:
city: Wirral
country: United Kingdom
facility: Clatterbridge Centre for Oncology NHS Foundation Trust
Study officials:
affiliation: The Clatterbridge Cancer Centre NHS Foundation Trust
name: Ernest Marshall
role: PRINCIPAL_INVESTIGATOR
References: