Clinical trial NCT01974752: Selumetinib (AZD6244: ARRY-142886) (Hyd-Sulfate) in Metastatic Uveal Melanoma (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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Metastatic
Uveal Melanoma
Keywords: uveal melanoma
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2013-11-03
Enrollment: 152
Sex: ALL
Minimum age (years): 18
Maximum age (years): 130
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Selumetinib therapy in patients with metastatic uveal melanoma.

Detailed 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)

Eligibility criteria: 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.

Primary outcomes:
measure: 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.
timeFrame: From Randomization, then every 6 weeks up until progression or death (whichever is sooner) assessed up to 15th May 2015
Secondary outcomes:
measure: 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
timeFrame: From Randomization, then every 6 weeks up until progression or death (whichever is sooner) assessed up to 15th May 2015
measure: 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
timeFrame: From Randomization, then every 6 weeks up until progression or death (whichever is sooner) assessed up to 15th May 2015
measure: Assessment of the Overall Survival (OS) in Patients Taking Selumetinib in Combination With Dacarbazine Compared With Those Taking Placebo in Combination With Dacarbazine
timeFrame: From Randomization, up until death assessed up to 15th May 2015
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Research Site
state: California
city: Aurora
country: United States
facility: Research Site
state: Colorado
city: Atlanta
country: United States
facility: Research Site
state: Georgia
city: Lutherville
country: United States
facility: Research Site
state: Maryland
city: St. Louis
country: United States
facility: Research Site
state: Missouri
city: New York
country: United States
facility: Research Site
state: New York
city: Philadelphia
country: United States
facility: Research Site
state: Pennsylvania
city: Edegem
country: Belgium
facility: Research Site
city: Gent
country: Belgium
facility: Research Site
city: Kortrijk
country: Belgium
facility: Research Site
city: Leuven
country: Belgium
facility: Research Site
city: Toronto
country: Canada
facility: Research Site
state: Ontario
city: Montreal
country: Canada
facility: Research Site
state: Quebec
city: Olomouc
country: Czech Republic
facility: Research Site
city: Praha
country: Czech Republic
facility: Research Site
city: Hus
country: Finland
facility: Research Site
city: Nice Cedex 2
country: France
facility: Research Site
city: Paris Cedex 5
country: France
facility: Research Site
city: Heidelberg
country: Germany
facility: Research Site
city: München
country: Germany
facility: Research Site
city: Jerusalem
country: Israel
facility: Research Site
city: Ramat Gan
country: Israel
facility: Research Site
city: Leiden
country: Netherlands
facility: Research Site
city: Barcelona
country: Spain
facility: Research Site
city: L'Hospitalet de Llobregat
country: Spain
facility: Research Site
city: Sevilla
country: Spain
facility: Research Site
city: Valencia
country: Spain
facility: Research Site
city: Glasgow
country: United Kingdom
facility: Research Site
city: Northwood
country: United Kingdom
facility: Research Site
city: Nottingham
country: United Kingdom
facility: Research Site
city: Swansea
country: United Kingdom
facility: Research Site
Study officials:
References:
citation: Carvajal RD, Piperno-Neumann S, Kapiteijn E, Chapman PB, Frank S, Joshua AM, Piulats JM, Wolter P, Cocquyt V, Chmielowski B, Evans TRJ, Gastaud L, Linette G, Berking C, Schachter J, Rodrigues MJ, Shoushtari AN, Clemett D, Ghiorghiu D, Mariani G, Spratt S, Lovick S, Barker P, Kilgour E, Lai Z, Schwartz GK, Nathan P. Selumetinib in Combination With Dacarbazine in Patients With Metastatic Uveal Melanoma: A Phase III, Multicenter, Randomized Trial (SUMIT). J Clin Oncol. 2018 Apr 20;36(12):1232-1239. doi: 10.1200/JCO.2017.74.1090. Epub 2018 Mar 12.
citation: Carvajal RD, Schwartz GK, Mann H, Smith I, Nathan PD. Study design and rationale for a randomised, placebo-controlled, double-blind study to assess the efficacy of selumetinib (AZD6244; ARRY-142886) in combination with dacarbazine in patients with metastatic uveal melanoma (SUMIT). BMC Cancer. 2015 Jun 10;15:467. doi: 10.1186/s12885-015-1470-z.