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

NCT ID: NCT01974752

Last Updated: 2017-01-05

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

152 participants

Study Classification

INTERVENTIONAL

Study Start Date

2014-04-30

Study Completion Date

2016-10-31

Brief Summary

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Selumetinib therapy in patients with metastatic uveal melanoma.

Detailed Description

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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)

Conditions

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Metastatic Uveal Melanoma

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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selumetinib 75mg twice daily

selumetinib 75mg twice daily in combination with dacarbazine.

Group Type EXPERIMENTAL

75mg selumetinib

Intervention Type DRUG

selumetinib tablets p.o. twice daily taken in combination with dacarbazine 1000mg/m2 iv on day 1 of every 21-day cycle.

Dacarbazine

Intervention Type DRUG

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.

placebo twice daily

placebo twice daily in combination with dacarbazine.

Group Type PLACEBO_COMPARATOR

placebo

Intervention Type DRUG

placebo tablets p.o. twice daily taken in combination with dacarbazine 1000mg/m2 iv on day 1 of every 21-day cycle.

Dacarbazine

Intervention Type DRUG

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.

Interventions

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75mg selumetinib

selumetinib tablets p.o. twice daily taken in combination with dacarbazine 1000mg/m2 iv on day 1 of every 21-day cycle.

Intervention Type DRUG

placebo

placebo tablets p.o. twice daily taken in combination with dacarbazine 1000mg/m2 iv on day 1 of every 21-day cycle.

Intervention Type DRUG

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.

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* 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

* 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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

130 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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AstraZeneca

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Research Site

Los Angeles, California, United States

Site Status

Research Site

Aurora, Colorado, United States

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Atlanta, Georgia, United States

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Lutherville, Maryland, United States

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St Louis, Missouri, United States

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New York, New York, United States

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Philadelphia, Pennsylvania, United States

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Research Site

Edegem, , Belgium

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Ghent, , Belgium

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Kortrijk, , Belgium

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Leuven, , Belgium

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Toronto, Ontario, Canada

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Montreal, Quebec, Canada

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Olomouc, , Czechia

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Prague, , Czechia

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Hus, , Finland

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Nice, , France

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Paris, , France

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Heidelberg, , Germany

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München, , Germany

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Jerusalem, , Israel

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Ramat Gan, , Israel

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Leiden, , Netherlands

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Barcelona, , Spain

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L'Hospitalet de Llobregat, , Spain

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Seville, , Spain

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Valencia, , Spain

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Glasgow, , United Kingdom

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Northwood, , United Kingdom

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Nottingham, , United Kingdom

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Swansea, , United Kingdom

Site Status

Countries

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United States Belgium Canada Czechia Finland France Germany Israel Netherlands Spain United Kingdom

References

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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.

Reference Type DERIVED
PMID: 29528792 (View on PubMed)

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.

Reference Type DERIVED
PMID: 26059332 (View on PubMed)

Other Identifiers

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D1344C00001

Identifier Type: -

Identifier Source: org_study_id

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