Assess Efficacy & Safety of Selumetinib in Combination With Docetaxel in Patients Receiving 2nd Line Treatment for v-Ki-ras2 Kirsten Rat Sarcoma Viral Oncogene Homolog (KRAS) Positive NSCLC (SELECT-1)

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by AstraZeneca
Sponsor:
Information provided by (Responsible Party):
AstraZeneca
ClinicalTrials.gov Identifier:
NCT01933932
First received: August 29, 2013
Last updated: July 10, 2014
Last verified: July 2014
  Purpose

The purpose of this study is to assess the efficacy of selumetinib in combination with docetaxel (75mg/m2) vs placebo in combination with docetaxel (75mg/m2) in patients with locally advance or metastatic NSCLCs that harbor mutations of KRAS. This study will also assess the PK, safety, patient reported outcomes (PRO) and tolerability profile of the selumetinib/docetaxel combination, compared to placebo in combination with docetaxel


Condition Intervention Phase
Locally Advanced or Metastatic Non Small Cell Lung Cancer Stage IIIb - IV
Drug: Selumetinib
Drug: Docetaxel
Drug: Placebo
Drug: Pegylated G-CSF
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase III, Double-Blind, Randomised, Placebo-Controlled Study to Assess the Efficacy and Safety of Selumetinib (AZD6244; ARRY-142886) (Hyd-Sulfate) in Combination With Docetaxel, in Patients Receiving Second Line Treatment for KRAS Mutation-Positive Locally Advanced or Metastatic Non Small Cell Lung Cancer (Stage IIIB - IV) (SELECT 1)

Resource links provided by NLM:


Further study details as provided by AstraZeneca:

Primary Outcome Measures:
  • Progression-Free Survival (PFS) [ Time Frame: Measured at baseline until the date of first documented objective disease progression. Estimated final completion : approximately 3 years after first subject in (FSI) ] [ Designated as safety issue: No ]
    Progression free survival is defined as the time from randomisation until the date of objective disease progression (RECIST 1.1) or death (by any cause in the absence of progression)


Secondary Outcome Measures:
  • Overall Survival (OS) [ Time Frame: Measured at baseline until date of death due to any cause. Estimated final completion : approximately 3.5 years after FSI ] [ Designated as safety issue: No ]
    Overall Survival is defined as the time from the date of randomisation until death due to any cause.

  • Objective Response Rate (ORR) [ Time Frame: Measured at baseline until the date of first documented objective disease progression.Estimated final completion : approximately 3 years after first subject in (FSI) ] [ Designated as safety issue: No ]
    ORR is defined as the number (%) of subjects with at least one visit response of complete response (CR) or partial response (PR).

  • Duration of Response (DoR) [ Time Frame: Measured from date of randomisation until 30 days post treatment discontinuation. Estimated final completion : approximately 3 years after first subject in (FSI) ] [ Designated as safety issue: No ]
    The symptom improvement rate will be defined as the number (%) of patients with two consecutive assessments at least 18 days apart (ie 21 days allowing a visit window of 3 days) which showed a clinically

  • Symptom improvement rate using Average Symptom Burden Index (ASBI) of the Lung Cancer Symptom Scale (LCSS) [ Time Frame: Measured from date of randomisation until 30 days post treatment discontinuation. Estimated final completion : approximately 3 years after first subject in (FSI) ] [ Designated as safety issue: No ]
    The symptom improvement rate will be defined as the number (%) of patients with two consecutive assessments at least 18 days apart (ie 21 days allowing a visit window of 3 days) which showed a clinically meaningful improvement in symptoms from baseline (defined as a decrease in the ASBI from baseline ≥10). LCSS-Lung Cancer Symptom Scale; ASBI-Average symptom burden index.

  • Time to symptom progression using Average Symptom Burden Index (ASBI) of the Lung Cancer Symptom Scale (LCSS) [ Time Frame: Measured from date of randomisation until 30 days post treatment discontinuation. Estimated final completion : approximately 3 years after first subject in (FSI) ] [ Designated as safety issue: No ]
    Time to symptom progression will be defined as the time from randomization until the date of first clinically meaningful symptom deterioration (defined as an increase in the ASBI from baseline ≥10), or death (by any cause). LCSS-Lung Cancer Symptom Scale; ASBI-Average symptom burden index.

  • Investigate safety and tolerability profile of Selumetinib in combination with docetaxel compared with placebo in combination with docetaxel by assessing of frequency of adverse events [ Time Frame: Measured from baseline until 30 days after the date of discontinuation of the last study treatment. Estimated final completion : approximately 3 years after first subject in (FSI) ] [ Designated as safety issue: Yes ]
    Adverse events graded according to the National Cancer Institute Common Terminology Criteria for AEs (CTCAE)

  • Investigate safety and tolerability profile of Selumetinib in combination with docetaxel compared with placebo in combination with docetaxel by assessing laboratory variables [ Time Frame: Measured from baseline until 30 days after the date of discontinuation of the last study treatment. Estimated final completion : approximately 3 years after first subject in (FSI) ] [ Designated as safety issue: Yes ]
    Laboratory parameter: Clinical chemistry, haematology and urinalysis

  • Investigate safety and tolerability profile of Selumetinib in combination with docetaxel compared with placebo in combination with docetaxel by assessing vital signs [ Time Frame: Measured from baseline until 30 days after the date of discontinuation of the last study treatment. Estimated final completion : approximately 3 years after first subject in (FSI) ] [ Designated as safety issue: Yes ]
    Vital signs assessments include weight, body temperature and supine blood pressure.

  • Investigate safety and tolerability profile of Selumetinib in combination with docetaxel compared with placebo in combination with docetaxel by assessing Echocardiogram (ECHO) / Multi Gated Acquisition (MUGA) scan [ Time Frame: Measured from baseline until 30 days after the date of discontinuation of the last study treatment. Estimated final completion : approximately 3 years after first subject in (FSI) ] [ Designated as safety issue: Yes ]
    Echocardiogram will be performed before the start of selumetinib therapy, every 12 weeks and as clinically indicated during the course of the study until 30 days after the last dose of selumetinib. If an echocardiogram scan cannot be taken, a MUGA scan will be conducted.

  • Investigate the pharmacokinetics (PK) of selumetinib and N-desmethyl selumetinib when administered in combination with docetaxel by assessing the area under plasma concentration time curve (AUC) [ Time Frame: PK blood samples will be collected pre-dose and up to 8 hours post-dose on day 1 and day 22. Estimated final completion : approximately 3 years after first subject in (FSI) ] [ Designated as safety issue: No ]
  • Investigate the pharmacokinetics (PK) of selumetinib and N-desmethyl selumetinib when administered in combination with docetaxel by assessing Cmax [ Time Frame: PK blood samples will be collected pre-dose and up to 8 hours post-dose on day 1 and day 22. Estimated final completion : approximately 3 years after first subject in (FSI) ] [ Designated as safety issue: No ]

Estimated Enrollment: 4225
Study Start Date: September 2013
Estimated Study Completion Date: March 2017
Estimated Primary Completion Date: July 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Selumetinib + Docetaxel
Three 25mg Selumetinib capsules will be administered orally uninterrupted twice daily in combination with docetaxel 75 mg/m2 intravenously administered on day 1 of each 21 day cycle
Drug: Selumetinib
Three 25 mg selumetinib capsules (Hyd-Sulfate) be administered orally, twice daily, (total dose 75 mg dose bd) on an uninterrupted schedule.
Other Name: AZD6244; ARRY-142886
Drug: Docetaxel
Docetaxel 75 mg/m2 will be administered intravenously on day 1 of each 21 day cycle.
Drug: Pegylated G-CSF
All patients will receive pegylated Granulocyte Colony Stimulating Factor (G-CSF) at least 24 hours after administration of every docetaxel dose and not within 14 days prior to the next docetaxel administration.
Other Name: Pegfilgrastim 6 mg
Experimental: Placebo + Docetaxel
Three placebo capsules will be administered orally uninterrupted twice daily in combination with docetaxel 75 mg/m2 intravenously administered on day 1 of each 21 day cycle.
Drug: Docetaxel
Docetaxel 75 mg/m2 will be administered intravenously on day 1 of each 21 day cycle.
Drug: Placebo
Three placebo capsules will be administered orally uninterrupted twice daily in combination with docetaxel 75 mg/m2 intravenously administered on day 1 of each 21 day cycle.
Drug: Pegylated G-CSF
All patients will receive pegylated Granulocyte Colony Stimulating Factor (G-CSF) at least 24 hours after administration of every docetaxel dose and not within 14 days prior to the next docetaxel administration.
Other Name: Pegfilgrastim 6 mg

Detailed Description:

A Phase III, Double-Blind, Randomised, Placebo-Controlled Study to Assess the Efficacy and Safety of Selumetinib (AZD6244; ARRY-142886) (Hyd-Sulfate) in Combination with Docetaxel, in Patients receiving second line treatment for KRAS Mutation-Positive Locally Advanced or Metastatic Non Small Cell Lung Cancer (Stage IIIB - IV) (SELECT-1)

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Provision of signed, written and dated informed 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)
  • KRAS mutation positive tumour sample as determined by the designated testing laboratory
  • Failure of 1st line anti-cancer therapy due to radiological documentation of disease progression in advanced disease or subsequent relapse of disease following 1st line therapy

Exclusion Criteria:

  • Mixed small cell and non-small cell lung cancer histology.
  • Received >1 prior anti-cancer drug regimen for advanced or metastatic NSCLC. Patients who develop disease progression while on switch maintenance therapy (maintenance using an agent not in the first-line regimen) will not be eligible.
  • Receiving or have received systemic anti-cancer therapy within 4 weeks prior to starting study treatment (6 weeks for nitrosoureas, mitomycin, and suramin) or any anti-cancer therapy which has not been cleared from the body by the time of starting study treatment.
  • Prior treatment with a Mitogen-Activated protein Kinase (MEK) inhibitor or any docetaxel-containing regimen (prior treatment with paclitaxel is acceptable).
  • Last radiation therapy within 4 weeks prior starting study treatment, or limited field of radiation for palliation within 7 days of the first dose of study treatment
  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: NCT01933932

Contacts
Contact: AstraZeneca Clinical Study Information 800-236-9933 ClinicalTrialTransparency@astrazeneca.com
Contact: AstraZeneca Cancer Study Locator Service 877-400-4656 astrazeneca@emergingmed.com

  Show 189 Study Locations
Sponsors and Collaborators
AstraZeneca
Investigators
Study Chair: Ian Smith, MD AstraZeneca UK, MSD
Principal Investigator: Pasi Jänne, MD Dana-Faber Cancer Institute, USA
  More Information

No publications provided

Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT01933932     History of Changes
Other Study ID Numbers: D1532C00079, 2013-001676-38
Study First Received: August 29, 2013
Last Updated: July 10, 2014
Health Authority: United States: Food and Drug Administration
Canada: Health Canada
Germany: Federal Institute for Drugs and Medical Devices
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia Medica
Russia: Ministry of Health of the Russian Federation
Hungary: National Institute of Pharmacy
Italy: The Italian Medicines Agency
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
United Kingdom: Medicines and Healthcare Products Regulatory Agency
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Bulgaria: Bulgarian Drug Agency
Chile: Instituto de Salud Pública de Chile
Ukraine: State Pharmacological Center - Ministry of Health
Brazil: National Health Surveillance Agency
Mexico: Federal Commission for Protection Against Health Risks
Israel: Ethics Commission
Australia: Department of Health and Ageing Therapeutic Goods Administration
Spain: Spanish Agency of Medicines
Romania: National Medicines Agency
Peru: Instituto Nacional de Salud
Turkey: Ministry of Health
Sweden: Medical Products Agency
Portugal: National Pharmacy and Medicines Institute
Austria: Federal Office for Safety in Health Care
Belgium: Federal Agency for Medicinal Products and Health Products

Keywords provided by AstraZeneca:
Mitogen-Activated Protein Kinase Kinase inhibitor; Non Small Cell Lung Cancer; metastatic; second line treatment for Non Small Cell Lung Cancer; KRAS mutation

Additional relevant MeSH terms:
Carcinoma, Non-Small-Cell Lung
Lung Neoplasms
Carcinoma, Bronchogenic
Bronchial Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Docetaxel
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 26, 2014