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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)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
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

Tracking Information
First Submitted Date  ICMJE March 8, 2013
First Posted Date  ICMJE March 12, 2013
Results First Submitted Date  ICMJE December 9, 2016
Results First Posted Date  ICMJE March 13, 2018
Last Update Posted Date March 13, 2018
Actual Study Start Date  ICMJE April 4, 2013
Actual Primary Completion Date January 4, 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 12, 2018)
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
Original Primary Outcome Measures  ICMJE
 (submitted: March 11, 2013)
  • Investigate safety, tolerability and recommended Phase II dose of selumetinib in combination with first line chemotherapy by assessing adverse events. [ Time Frame: Adverse events will be collected from consent until 28 days after the last dose of selumetinib, 180 days for the average patient ]
  • Investigate safety, tolerability and recommended Phase II dose of selumetinib in combination with first line chemotherapy by assessing physical examination, pulse and blood pressure [ Time Frame: Physical exam, pulse and blood pressure will be assessed every 3 weeks from start of selumetinib therapy until 28 days after the last dose of selumetinib, 180 days for the average patient ]
  • Investigate safety, tolerability and recommended Phase II dose of selumetinib in combination with first line chemotherapy by assessing laboratory variables [ Time Frame: Laboratory parameters will be assessed every 3 weeks from start of selumetinib therapy until 28 days after the last dose of selumetinib, 180 days for the average patient ]
  • Investigate safety, tolerability and recommended Phase II dose of selumetinib in combination with first line chemotherapy by assessing eye examinations and ECG. [ Time Frame: Eye examinations and ECG will be performed before the start of selumetinib therapy and as clinically indicated until 28 days after the last dose of selumetinib, 180 days for the average patient ]
  • Investigate safety, tolerability and recommended Phase II dose of selumetinib in combination with first line chemotherapy by assessing LVEF [ Time Frame: LVEF will be assessed every 12 weeks from start of selumetinib therapy until 28 days after the last dose of selumetinib, 180 days for the average patient ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 12, 2018)
  • 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
  • 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
  • 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
  • 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
  • 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)
  • 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
  • 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
  • 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
Original Secondary Outcome Measures  ICMJE
 (submitted: March 11, 2013)
  • Rate and extent of absorption of selumetinib at steady state when administered with doublet chemotherapy, by assessment of a range of PK parameters (including AUC and Cmax) of selumetinib. [ Time Frame: PK blood samples will be collected pre-dose and up to 10 hours post-dose on Cycle 1 Day 8 and on Cycle 2 Day 1 for cohorts where cisplatin is not administered on Day 8 of a cycle ]
  • Rate and extent of absorption of chemotherapies (gemcitabine, cisplatin and carboplatin [if applicable]) when infusion given in combination with selumetinib by assessment of PK parameters (AUC) of gemcitabine or platinum (cisplatin and carboplatin). [ Time Frame: PK blood samples will be collected before, during and at the end of infusion and up to 9.5 (gemcitabine), 7.5 (cisplatin) or 5.5 (carboplatin) hours after the end of infusion on Cycle 1 Day 8 and/or Cycle 2 Day depending on the cohort. ]
  • Efficacy assessed by tumour response (objective response rate) assessed using RECIST 1.1 [ Time Frame: Tumour assessment by RECIST 1.1 at baseline and every 6 weeks thereafter until the end of selumetinib treatment, 180 days for the average patient ]
  • Efficacy assessed by tumour response (best overall response) assessed using RECIST 1.1 [ Time Frame: Tumour assessment by RECIST 1.1 at baseline and every 6 weeks thereafter until the end of selumetinib treatment, 180 days for the average patient ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Assess Safety & Efficacy of Selumetinib When Given in Combination With Standard First Line Treatment for Advanced Non-small Cell Lung Cancer
Official Title  ICMJE 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)
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.

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)
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Locally Advanced or Metastatic NSCL Cancer Stage IIIB IV
Intervention  ICMJE
  • 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.
Study Arms  ICMJE Experimental: Selumetinib+standard chemotherapy
Selumetinib plus gemcitabine; or pemetrexed and cisplatin or carboplatin
Interventions:
  • Drug: selumetinib
  • Drug: gemcitabine
  • Drug: cisplatin
  • Drug: carboplatin
  • Drug: pemetrexed
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: March 12, 2018)
55
Original Estimated Enrollment  ICMJE
 (submitted: March 11, 2013)
18
Actual Study Completion Date  ICMJE January 4, 2016
Actual Primary Completion Date January 4, 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 99 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United Kingdom
Removed Location Countries Germany,   Spain
 
Administrative Information
NCT Number  ICMJE NCT01809210
Other Study ID Numbers  ICMJE D1532C00070
EudraCT number: 2012-005202-22
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party AstraZeneca
Study Sponsor  ICMJE AstraZeneca
Collaborators  ICMJE Not Provided
Investigators  ICMJE
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
PRS Account AstraZeneca
Verification Date March 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP