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

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2014 by AstraZeneca
Sponsor:
Information provided by (Responsible Party):
AstraZeneca
ClinicalTrials.gov Identifier:
NCT01974752
First received: October 10, 2013
Last updated: October 31, 2014
Last verified: October 2014
  Purpose

Selumetinib therapy in patients with metastatic uveal melanoma.


Condition Intervention Phase
Metastatic
Uveal Melanoma
Drug: 75mg selumetinib
Drug: placebo
Drug: Dacarbazine
Phase 3

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

Resource links provided by NLM:


Further study details as provided by AstraZeneca:

Primary Outcome Measures:
  • Progression Free Survival (PFS) by Blind Independent Central Review (BICR) according to RECIST 1.1 [ Time Frame: Radiological scans performed from baseline then every 6 weeks until disease progression is confirmed by BICR in accordance with RECIST 1.1, assessed up to 18 months ] [ Designated as safety issue: No ]
    To assess the efficacy of selumetinib in combination with dacarbazine with placebo in combination with dacarbazine in terms of PFS


Secondary Outcome Measures:
  • Objective Response Rate (ORR) by central review of RECIST data [ Time Frame: From baseline and at every 6 weeks, up to 18 months ] [ Designated as safety issue: No ]
    To assess the efficacy of selumetinib in combination with dacarbazine with placebo in combination with dacarbazine by assessment of Objective Response Rate

  • Duration of Response by central review of RECIST data. [ Time Frame: From baseline and at every 6 weeks, up to 18 months ] [ Designated as safety issue: No ]
    To assess the efficacy of selumetinib in combination with dacarbazine with placebo in combination with dacarbazine by assessment of Duration of response

  • Change in tumour size by central review of RECIST data. [ Time Frame: From baseline and at every 6 weeks, up to 18 months ] [ Designated as safety issue: No ]
    To assess the efficacy of selumetinib in combination with dacarbazine with placebo in combination with dacarbazine by assessment of change in tumour size

  • Efficacy in patients by assessment of overall survival [ Time Frame: Post -progression patients assessed for survival every 8 weeks, up to 30 months ] [ Designated as safety issue: No ]
    To assess Overall survival in patients taking selumetinib in combination with dacarbazine compared with those taking placebo in combination with dacarbazine

  • Assessment of the safety and tolerability of selumetinib by collection of adverse event reports [ Time Frame: From baseline and at each study visit up to 30 months ] [ Designated as safety issue: Yes ]
    Assessment of adverse events (AEs) graded by Common Terminology Criteria for Adverse Events (CTCAE) v4.0

  • Determine safety and tolerability of selumetinib by assessment of 12 lead electrocardiograms [ Time Frame: From baseline, up to 30 months ] [ Designated as safety issue: Yes ]
    Assessment of standard 12 lead electrocardiograms (ECGs)

  • Determine safety and tolerability of selumetinib by assessment of vital signs [ Time Frame: From baseline and at each study visit up to 30 months ] [ Designated as safety issue: Yes ]
    Assessment of standard vital signs (including blood pressure, pulse)

  • Determine safety and tolerability of selumetinib by assessment of clinical chemistry results [ Time Frame: From baseline and at each study visit up to 30 months ] [ Designated as safety issue: Yes ]
    Assessment of laboratory parameters (clinical chemistry)

  • Determine safety and tolerability of selumetinib by assessment of haematology results [ Time Frame: From baseline and at each study visit up to 30 months ] [ Designated as safety issue: Yes ]
    Assessment of laboratory parameters (haematology)

  • Determine safety and tolerability of selumetinib by assessment of urinalysis results [ Time Frame: From baseline and at each study visit up to 30 months ] [ Designated as safety issue: Yes ]
    Assessment of laboratory parameters (urinalysis)

  • Determine safety and tolerability of selumetinib by assessment of Echocardiogram/Multi gated Acquisition Scan (MUGA) [ Time Frame: From baseline and every 12 weeks up to 30 months. ] [ Designated as safety issue: Yes ]
    Assessment of MUGA

  • Determine safety and tolerability of selumetinib by Ophthalmologic assessment [ Time Frame: From baseline, up to 30 months ] [ Designated as safety issue: Yes ]
    Ophthalmological assessment


Estimated Enrollment: 128
Study Start Date: April 2014
Estimated Study Completion Date: January 2016
Estimated Primary Completion Date: April 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: selumetinib 75mg twice daily
selumetinib 75mg twice daily in combination with dacarbazine.
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.
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.
Placebo Comparator: placebo twice daily
placebo twice daily in combination with dacarbazine.
Drug: placebo
placebo tablets p.o. twice daily taken in combination with dacarbazine 1000mg/m2 iv on day 1 of every 21-day cycle.
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.

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01974752

Contacts
Contact: AstraZeneca Clinical Study Information Center 1-877-240-9479 information.center@astrazeneca.com
Contact: Cancer Study Locator 877 400 4656 AstraZeneca@emergingmed.com

  Show 50 Study Locations
Sponsors and Collaborators
AstraZeneca
  More Information

No publications provided

Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT01974752     History of Changes
Other Study ID Numbers: D1344C00001
Study First Received: October 10, 2013
Last Updated: October 31, 2014
Health Authority: France: *National Agency for the Safety of Medicine and Health Products.*
Belgium: Federal Agency for Medicinal Products and Health Products
Netherlands: Medicines Evaluation Board (MEB)
Israel: *Regulations of Ministry of Health.*
Germany: Federal Institute for Drugs and Medical Devices
Czech Republic: State Institute for Drug Control
United Kingdom: Medicines and Healthcare Products Regulatory Agency
United States: Food and Drug Administration

Keywords provided by AstraZeneca:
uveal melanoma

Additional relevant MeSH terms:
Melanoma
Uveal Neoplasms
Eye Diseases
Eye Neoplasms
Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Germ Cell and Embryonal
Neoplasms, Nerve Tissue
Neuroectodermal Tumors
Neuroendocrine Tumors
Nevi and Melanomas
Uveal Diseases

ClinicalTrials.gov processed this record on November 23, 2014