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Assess Safety & Efficacy of Selumetinib When Given in Combination With Standard First Line Treatment for Advanced Non-small Cell Lung Cancer (SELECT-3)

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ClinicalTrials.gov Identifier: NCT01809210
Recruitment Status : Completed
First Posted : March 12, 2013
Results First Posted : March 13, 2018
Last Update Posted : March 13, 2018
Sponsor:
Information provided by (Responsible Party):
AstraZeneca

Brief Summary:

This is a Phase I, open label multicentre study of selumetinib administered orally in combination with first line chemotherapy regimens to patients with advanced/metastatic NSCLC. The study has been designed to allow an investigation of the optimal dose of selumetinib in combination with various standard first line double-platinum chemotherapy regimens. Initial assessment will be based on tolerability of selumetinib in combination with one or more selected regimens that are considered to be tolerated also being assessed for preliminary evidence of activity.

This study is a dose finding and optional cohort expansion; In addition all patients will be assessed for anti-cancer efficacy of the combination of selumetinib and chemotherapy.


Condition or disease Intervention/treatment Phase
Locally Advanced or Metastatic NSCL Cancer Stage IIIB IV Drug: selumetinib Drug: gemcitabine Drug: cisplatin Drug: carboplatin Drug: pemetrexed Phase 1

Detailed Description:
A Phase I, Open Label, Multicentre Study to Assess the Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of Selumetinib (AZD6244; ARRY-142886) in Combination with First Line Chemotherapy Regimens in Patients with Non-Small Cell Lung Cancer (NSCLC)

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 55 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I, Open Label, Multicentre Study to Assess the Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of Selumetinib (AZD6244; ARRY-142886) in Combination With First Line Chemotherapy Regimens in Patients With Non-Small Cell Lung Cancer (NSCLC)
Actual Study Start Date : April 4, 2013
Actual Primary Completion Date : January 4, 2016
Actual Study Completion Date : January 4, 2016

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Selumetinib+standard chemotherapy
Selumetinib plus gemcitabine; or pemetrexed and cisplatin or carboplatin
Drug: selumetinib
2 x 25mg capsules bd continuously in cohort 1 (with gemcitabine and cisplatin). If tolerated - next cohort 3 x 25mg capsules bd continuously. if higher doses are explored, required number of capsules will be provided. Option to administer on D2-19 of each 21 day cycle if required to assess tolerability of combinations with chemotherapy

Drug: gemcitabine
1250 mg/m2 iv on Day 1 and 8 of each 21 day cycle. If combination not tolerated, option to give 1000 mg/m2 iv on Day 1 and Day 8 of each 21 day cycle

Drug: cisplatin
75 mg/m2 iv on Day 1 of each 21 day cycle. If combination not tolerated, option to give 50 mg/m2 iv on Day 1 or 25mg/m2 iv on Day 1 and Day 8 of each 21 day cycle

Drug: carboplatin
If it is not possible to identify a tolerable combination of selumetinib, gemcitabine and cisplatin, cisplatin may be replaced with carboplatin (AUC5) iv on Day 1 of each 21 day cycle

Drug: pemetrexed
Gemcitabine may be replaced with pemetrexed 500 mg/m2 iv on Day 1 of each 21 day cycle.




Primary Outcome Measures :
  1. Dose Limiting Toxicity (DLT) Events in Chemotherapy in Combination With Selumetinib [ Time Frame: The first dose on Cycle 1 Day 1 up to the time before dosing on Cycle 2 Day 1, assessed up to 3 weeks ]
    Any toxicity not attributable to the disease or disease-related processess under investigation, considered related to the combination of chemotherapy plus selumetinib, which occurs within the timeframe and is dose limiting


Secondary Outcome Measures :
  1. Best Objective Response [ Time Frame: Screening, week 6 and week 12 ]
    The best response a patient has had during their time in the study up until RECIST progression or last valuable assessment in the absence of RECIST progression. Per Response Evaluation Criteria In Solid Tumours (RECIST version 1.1) for target lesions (TL) and assessed by MRI or CT: Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD), neither sufficient shrinkage to qualify for a Partial Response nor sufficient increase to qualify for Progressive Disease (PD); Progressive Disease (PD), >=20% increase in the sum of the longest diameter of target lesions, the sum must also demonstrate an absolute increase of >=5mm; Complete Response (CR), disappearance of all target lesions, any pathological lymph nodes selected as TLs must have a reduction in short axis to <10mm

  2. Percentage Change From Baseline at 6 Weeks in Target Lesion Size [ Time Frame: Week 6 ]
    The percentage change in the sum of the diameters of target lesions

  3. Best Percentage Change From Baseline in Target Lesion Size [ Time Frame: Screening, week 6 and week 12 ]
    The best percentage change in tumour size a patient has had during their time in the study up until RECIST progression or last valuable assessment in the absence of RECIST progression. Percentage change was derived at each visit by the percentage change in the sum of the diameters of target lesions

  4. Objective Response Rate (ORR) [ Time Frame: Up until progression or last evaluable assessment in the absence of progression, up to 9 months ]
    The number of patients who had at least 1 confirmed visit response of Complete Response (CR) or Partial Response (PR) prior to any evidence of progression. Per Response Evaluation Criteria In Solid Tumours (RECIST version 1.1) for target lesions (TL) and assessed by MRI or CT: Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Complete Response (CR), disappearance of all target lesions, any pathological lymph nodes selected as TLs must have a reduction in short axis to <10mm; Objective Response Rate (ORR) = CR + PR

  5. AUC (0-tau) [ Time Frame: Cycle 2 Day1, pre-dose, 0.5, 1, 1.5, 2, 4, 8, 10 hours post dose ]
    Area under the concentration time curve (AUC) over a dosing interval at steady state (0-tau)

  6. Cmax,ss [ Time Frame: Cycle 2 Day1, pre-dose, 0.5, 1, 1.5, 2, 4, 8, 10 hours post dose ]
    Maximum plasma concentration at steady state

  7. Tmax,ss [ Time Frame: Cycle 2 Day1, pre-dose, 0.5, 1, 1.5, 2, 4, 8, 10 hours post dose ]
    Time to reach maximum plasma concentration at steady state

  8. CL/F [ Time Frame: Cycle 2 Day1, pre-dose, 0.5, 1, 1.5, 2, 4, 8, 10 hours post dose ]
    Apparent oral plasma clearance



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Ages Eligible for Study:   18 Years to 99 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Provision of signed, written and dated consent prior to any study specific procedures
  • Male or female, aged 18 years or older
  • Histological or cytological confirmation of locally advanced or metastatic NSCLC (IIIB-IV)
  • Female patients must not be breast-feeding and have a negative pregnancy test prior to start of dosing or must have evidence of non-child-bearing potential
  • Patients must be eligible to receive treatment with the platinum doublet combination with which selumetinib is being combined and in accordance with the local product information

Exclusion Criteria:

  • Prior chemotherapy or other systemic anti-cancer treatment for advanced NSCLC.
  • Prior surgery or radiotherapy within 6 months or palliative radiotherapy within 4 weeks of start of study treatment.
  • Female patients who are breast-feeding or male or female patients of reproductive potential who are not employing an effective method of birth control
  • Another primary malignancy within 5 years of starting study treatment, except for adequately treated basal or squamous cell carcinoma of the skin or cancer of the cervix in situ.
  • As judged by the Investigator, any evidence of severe or uncontrolled systemic diseases, active bleeding diatheses, renal transplant, or active infection

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01809210


Locations
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United Kingdom
Research Site
Glasgow, United Kingdom, G12 0YN
Research Site
London, United Kingdom, W1G 6AD
Research Site
Manchester, United Kingdom, M20 4BX
Research Site
Newcastle upon Tyne, United Kingdom, NE7 7DN
Sponsors and Collaborators
AstraZeneca
Investigators
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Study Director: Gabriella Mariani, MD AstraZeneca UK, MSD
Principal Investigator: Emma Dean, BMEDSCI, BM, BS, PHD The Christie NHS Foundation Trust, UK
Principal Investigator: Fiona Blackhall, PhD, FRCP The Christie NHS Foundation Trust Clinical Trials Unit; UK

Additional Information:
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Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT01809210     History of Changes
Other Study ID Numbers: D1532C00070
EudraCT number: 2012-005202-22
First Posted: March 12, 2013    Key Record Dates
Results First Posted: March 13, 2018
Last Update Posted: March 13, 2018
Last Verified: March 2018

Keywords provided by AstraZeneca:
MEK1/2 inhibitor,
Non Small Cell Lung Cancer,
metastatic,
first line treatment for Non Small Cell Lung Cancer

Additional relevant MeSH terms:
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Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Gemcitabine
Cisplatin
Carboplatin
Pemetrexed
Antineoplastic Agents
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Folic Acid Antagonists
Nucleic Acid Synthesis Inhibitors