Clinical trial NCT01809210: Assess Safety & Efficacy of Selumetinib When Given in Combination With Standard First Line Treatment for Advanced Non-small Cell Lung Cancer
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Locally Advanced or Metastatic NSCL Cancer Stage IIIB IV
Keywords: MEK1/2 inhibitor,
Non Small Cell Lung Cancer,
metastatic,
first line treatment for Non Small Cell Lung Cancer
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2013-03-12
Enrollment: 55
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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)

Eligibility 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

Primary outcomes:
measure: Dose Limiting Toxicity (DLT) Events in Chemotherapy in Combination With Selumetinib
timeFrame: The first dose on Cycle 1 Day 1 up to the time before dosing on Cycle 2 Day 1, assessed up to 3 weeks
Secondary outcomes:
measure: Best Objective Response
timeFrame: Screening, week 6 and week 12
measure: Percentage Change From Baseline at 6 Weeks in Target Lesion Size
timeFrame: Week 6
measure: Best Percentage Change From Baseline in Target Lesion Size
timeFrame: Screening, week 6 and week 12
measure: Objective Response Rate (ORR)
timeFrame: Up until progression or last evaluable assessment in the absence of progression, up to 9 months
measure: AUC (0-tau)
timeFrame: Cycle 2 Day1, pre-dose, 0.5, 1, 1.5, 2, 4, 8, 10 hours post dose
measure: Cmax,ss
timeFrame: Cycle 2 Day1, pre-dose, 0.5, 1, 1.5, 2, 4, 8, 10 hours post dose
measure: Tmax,ss
timeFrame: Cycle 2 Day1, pre-dose, 0.5, 1, 1.5, 2, 4, 8, 10 hours post dose
measure: CL/F
timeFrame: Cycle 2 Day1, pre-dose, 0.5, 1, 1.5, 2, 4, 8, 10 hours post dose
Other outcomes:
Locations:
city: Glasgow
country: United Kingdom
facility: Research Site
city: London
country: United Kingdom
facility: Research Site
city: Manchester
country: United Kingdom
facility: Research Site
city: Newcastle upon Tyne
country: United Kingdom
facility: Research Site
Study officials:
affiliation: AstraZeneca UK, MSD
name: Gabriella Mariani, MD
role: STUDY_DIRECTOR
affiliation: The Christie NHS Foundation Trust, UK
name: Emma Dean, BMEDSCI, BM, BS, PHD
role: PRINCIPAL_INVESTIGATOR
affiliation: The Christie NHS Foundation Trust Clinical Trials Unit; UK
name: Fiona Blackhall, PhD, FRCP
role: PRINCIPAL_INVESTIGATOR
References: