Selumetinib (AZD6244: ARRY-142886) (Hyd-Sulfate) in Metastatic Uveal Melanoma (SUMIT)

Uveal Melanoma Clinical Trial

— SUMIT  

Official title:

A Randomised, Double-Blind Study to Assess the Efficacy of Selumetinib (AZD6244: ARRY-142886) (Hyd-Sulfate) in Combination With Dacarbazine Compared With Placebo in Combination With Dacarbazine as First Systemic Therapy in Patients With Metastatic Uveal Melanoma (SUMIT)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01974752
• Other study ID #: D1344C00001
• Status: Completed
• Phase: Phase 3
• First received: October 10, 2013
• Last updated: January 4, 2017
• Start date: April 2014
• Est. completion date: October 2016

Study information

• Verified date: January 2017
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: *National Agency for the Safety of Medicine and Health Products.*Belgium: Federal Agency for Medicinal Products and Health ProductsNetherlands: Medicines Evaluation Board (MEB)Israel: *Regulations of Ministry of Health.*Germany: Federal Institute for Drugs and Medical DevicesCzech Republic: State Institute for Drug ControlUnited Kingdom: Medicines and Healthcare Products Regulatory AgencyUnited States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

Selumetinib therapy in patients with metastatic uveal melanoma.

Description:

A randomised double-blind study to assess the efficacy of selumetinib (AZD6244, Hyd-Sulfate) in combination with Dacarbazine compared with placebo in combination with Dacarbazine as first systemic therapy in patients with metastatic uveal melanoma (SUMIT)

Recruitment information / eligibility

• Status: Completed
• Enrollment: 152
• Est. completion date: October 2016
• Est. primary completion date: May 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 130 Years

Eligibility

Inclusion Criteria: Clinical diagnosis of metastatic uveal melanoma; Written consent from female or male patients aged 18 years and over. Histological or cytological confirmation of melanoma who are suitable for treatment with dacarbazine chemotherapy.

• At least one lesion that can be accurately measured at baseline as>/=10mm in the longest diameter. (except lymph nodes which must have short axis =15 mm) with CT or MRI and which is suitable for accurate repeated measurements

• ECOG performance status 0-1

• life expectancy >12 weeks

• Normal organ and marrow function

• Evidence of post-menopausal status, or negative urinary or serum pregnancy test for female pre-menopausal patients

• Patients should be able to swallow selumetinib/placebo capsules

Exclusion Criteria:-Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site)

• Previous randomisation in the present study

• Patients cannot have previously been treated with a systemic anti-cancer therapy. Patients can have prior intra-hepatic or non-systemic therapy. -Having received any of the following within the specified timeframe:

Any prior systemic anti-cancer therapy for the treatment of this current diagnosis, An investigational drug within 30 days of starting treatment or within five half-lives of the compound (whichever is the most appropriate is at the discretion of the Investigator), or have not recovered from side effects of an investigational drug Any non-systemic anti-cancer therapy which has not been cleared from the body by the time of starting study treatment Radiation therapy within 4 weeks prior to starting study treatment, or limited field of radiation for palliation within 7 days of the first dose of study treatment Major surgery within 4 weeks prior to entry into the study (excluding the placement of vascular access) which would prevent administration of study treatment, Any prior investigational therapy comprising inhibitors of RAS, RAF or MEK at any time, Previous treatment with dacarbazine. Any unresolved toxicity >CTCAE grade 2 from previous anti-cancer therapy, excluding alopecia -History of allergic reactions attributed to compounds of similar chemical or biologic composition to selumetinib or dacarbazine

--Symptomatic brain metastases or spinal cord compression (patients must be treated and stable off steroids and anti-convulsants for at least 1 month prior to entry into the study)

Cardiac conditions as follows:

• Uncontrolled hypertension (BP =150/95 mmHg despite medical therapy)

• Acute coronary syndrome within 6 months prior to starting treatment

• Uncontrolled Angina - Canadian Cardiovascular Society grade II-IV despite medical therapy - Symptomatic heart failure (New York Heart Association [NYHA] Class II-IV,- Prior or current cardiomyopathy

• Baseline LVEF <55% measured by echocardiography or MUGA. Appropriate correction to be used if a MUGA is performed

• Severe valvular heart disease

• Atrial fibrillation with a ventricular rate >100 bpm on ECG at rest

• QTcF >450 ms or other factors that increase the risk of QTc prolongation

• Any evidence of severe or uncontrolled systemic disease, active infection, active bleeding diatheses or renal transplant, including any patient known to have hepatitis B, hepatitis C or human immunodeficiency virus (HIV)

• Refractory nausea and vomiting, chronic gastrointestinal diseases (eg inflammatory bowel disease), or significant bowel resection that would preclude adequate absorption

• History of another primary malignancy within 5 years prior to starting study treatment, except for adequately treated basal or squamous cell carcinoma of the skin or cancer of the cervix in situ and the disease under study

• Ophthalmologic conditions:

• Current or past history of central serous retinopathy

• Current or past history of retinal vein occlusion

• IOP >21 mmHg or uncontrolled glaucoma (irrespective of IOP)

• Female patients who are breast-feeding a child and male or female patients of reproductive potential who are not employing an effective method of birth control

• Clinical judgement by the Investigator that the patient should not participate in the study.

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Melanoma
• Metastatic
• Uveal Melanoma
• Uveal Neoplasms

Intervention

Drug:
• 75mg selumetinib
selumetinib tablets p.o. twice daily taken in combination with dacarbazine 1000mg/m2 iv on day 1 of every 21-day cycle.
• placebo
placebo tablets p.o. twice daily taken in combination with dacarbazine 1000mg/m2 iv on day 1 of every 21-day cycle.
• Dacarbazine
dacarbazine 1000mg/m2 iv on day 1 of every 21-day cycle taken in combination with either selumetinib or placebo tablets p.o. twice daily.

Locations

Country	Name	City	State
Belgium	Research Site	Edegem
Belgium	Research Site	Gent
Belgium	Research Site	Kortrijk
Belgium	Research Site	Leuven
Canada	Research Site	Montreal	Quebec
Canada	Research Site	Toronto	Ontario
Czech Republic	Research Site	Olomouc
Czech Republic	Research Site	Praha
Finland	Research Site	Hus
France	Research Site	Nice Cedex 2
France	Research Site	Paris Cedex 5
Germany	Research Site	Heidelberg
Germany	Research Site	München
Israel	Research Site	Jerusalem
Israel	Research Site	Ramat Gan
Netherlands	Research Site	Leiden
Spain	Research Site	Barcelona
Spain	Research Site	L'Hospitalet de Llobregat
Spain	Research Site	Sevilla
Spain	Research Site	Valencia
United Kingdom	Research Site	Glasgow
United Kingdom	Research Site	Northwood
United Kingdom	Research Site	Nottingham
United Kingdom	Research Site	Swansea
United States	Research Site	Atlanta	Georgia
United States	Research Site	Aurora	Colorado
United States	Research Site	Los Angeles	California
United States	Research Site	Lutherville	Maryland
United States	Research Site	New York	New York
United States	Research Site	Philadelphia	Pennsylvania
United States	Research Site	St. Louis	Missouri

Sponsors (1)

Lead Sponsor	Collaborator
AstraZeneca

Countries where clinical trial is conducted

United States,  Belgium,  Canada,  Czech Republic,  Finland,  France,  Germany,  Israel,  Netherlands,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Assessment of the Efficacy of Selumetinib in Combination With Dacarbazine Compared With Placebo in Combination With Dacarbazine Measured as Progression Free Survival (PFS) Using BICR According to RECIST 1.1.	Progression free survival (PFS) using blinded independent central review (BICR) according to the Response Evaluation Criteria in Solid Tumours version 1.1 (RECIST 1.1). Progression is defined as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.	From Randomization, then every 6 weeks up until progression or death (whichever is sooner) assessed up to 15th May 2015	No
Secondary	Assessment of the Efficacy of Selumetinib in Combination With Dacarbazine Compared With Placebo in Combination With Dacarbazine in Terms of Objective Response Rate (ORR) by BICR	ORR at Week 6 using BICR according to RECIST 1.1	From Randomization, then every 6 weeks up until progression or death (whichever is sooner) assessed up to 15th May 2015	No
Secondary	Assessment of the Efficacy of Selumetinib in Combination With Dacarbazine Compared With Placebo in Combination With Dacarbazine in Terms of Change in Tumour Size at Week 6 by BICR	Percent change in tumour size at Week 6 using BICR according to RECIST 1.1	From Randomization, then every 6 weeks up until progression or death (whichever is sooner) assessed up to 15th May 2015	No
Secondary	Assessment of the Overall Survival (OS) in Patients Taking Selumetinib in Combination With Dacarbazine Compared With Those Taking Placebo in Combination With Dacarbazine	Overall Survival	From Randomization, up until death assessed up to 15th May 2015	No