AZD6244 in Combination With Docetaxel Versus Docetaxel Alone in KRAS Mutation Positive NSCLC Patients

NCT ID: NCT00890825

Last Updated: 2018-06-20

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

88 participants

Study Classification

INTERVENTIONAL

Study Start Date

2009-04-20

Study Completion Date

2016-11-02

Brief Summary

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The purpose of this study is to compare the efficacy of AZD6244 in combination with docetaxel versus docetaxel alone in patients with KRAS mutation positive locally advanced or metastatic non small cell lung cancer.

Detailed Description

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The primary objective of this study was to assess the efficacy in terms of overall survival (OS) of AZD6244 in combination with docetaxel, compared with docetaxel alone, in second-line patients with KRAS mutation-positive locally advanced or metastatic NSCLC. Amendment 4 of the CSP altered the primary objective and outcome variable from progression-free survival (PFS) to OS, and the secondary outcome variable changed from OS to PFS.

The secondary objectives of the study were:

* To further assess the efficacy of AZD6244 in combination with docetaxel, compared with docetaxel alone, in second-line patients with KRAS mutation-positive locally advanced or metastatic NSCLC
* To assess the safety and tolerability profile of AZD6244 in combination with docetaxel
* To investigate the use of plasma and serum as a potential source of circulating free tumour DNA (cfDNA) for the analysis of KRAS mutation status
* To investigate the PK of AZD6244 and N-desmethyl AZD6244 and any other known metabolites when AZD6244 is administered in combination with docetaxel.

The exploratory objectives of the study were:

* To assess the prevalence, severity and change over time of advanced NSCLC cancer specific symptoms in patients receiving AZD6244 in combination with docetaxel and docetaxel alone
* To explore potential biomarkers in residual tumour, plasma and/or serum taken for KRAS mutational analysis which may influence development of NSCLC (and associated clinical characteristics) and/or response (optional)
* To investigate the relationship between AZD6244 and/or N-desmethyl AZD6244 and any other known metabolite plasma concentrations or exposure and clinical outcomes, efficacy, AEs, and/or safety parameters if deemed appropriate
* To collect and store deoxyribonucleic acid (DNA), derived from a blood sample, for future exploratory research into genes that may influence response, eg, distribution, safety, tolerability, and efficacy of AZD6244 and/or agents used in combination and/or as comparators (optional).

Conditions

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Non Small Cell Lung Cancer

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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AZD6244 + Docetaxel

AZD6244 75 mg bd + Docetaxel 75 mg/m\^2

Group Type ACTIVE_COMPARATOR

AZD6244

Intervention Type DRUG

oral capsules, 75mg twice daily

docetaxel

Intervention Type DRUG

75mg/m2 iv on day 1 of every 21 day cycle

Placebo + Docetaxel

Placebo + Docetaxel 75 mg/m\^2

Group Type PLACEBO_COMPARATOR

docetaxel

Intervention Type DRUG

75mg/m2 iv on day 1 of every 21 day cycle

Placebo

Intervention Type DRUG

placebo

Interventions

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AZD6244

oral capsules, 75mg twice daily

Intervention Type DRUG

docetaxel

75mg/m2 iv on day 1 of every 21 day cycle

Intervention Type DRUG

Placebo

placebo

Intervention Type DRUG

Other Intervention Names

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Selumetinib Taxotere

Eligibility Criteria

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Inclusion Criteria

* Locally advanced or metastatic non small cell lung cancer (IIIB-IV)
* Failure of first line anti-cancer therapy (either radiological documentation of disease progression or due to toxicity) in advanced disease or subsequent relapse of disease following first line therapy
* Tumour sample confirmed as KRAS mutation positive (Note: Sample must be available upon enrolment to ship to AZ appointed central laboratory, or mutation status confirmed locally at AstraZeneca agreed local laboratory using agreed methodology, or mutation status confirmed by an accredited (eg CLIA certified) commercial laboratory (eg Genzyme or Lab 21).

Exclusion Criteria

* Received \>1 prior anti-cancer therapy for advanced or metastatic non small cell lung cancer (excluding radiotherapy)
* Prior treatment with a MEK inhibitor or any docetaxel containing regimen (prior treatment with paclitaxel is acceptable)
* Having received an investigational drug within 30 days of starting treatment, or have not recovered from side effects of an investigational drug
* Brain metastases or spinal cord compression unless asymptomatic, treated and stable off steroids and anti-convulsants for at least 1 month
Minimum Eligible Age

18 Years

Maximum Eligible Age

130 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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AstraZeneca

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Dr. Pasi Janne

Role: PRINCIPAL_INVESTIGATOR

Dana-Farber Cancer Institute, Boston, USA

Dr. Gabriella Mariani

Role: STUDY_DIRECTOR

AstraZeneca, Hertfordshire, UK

Locations

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Research Site

Los Angeles, California, United States

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Aurora, Colorado, United States

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Boston, Massachusetts, United States

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Columbus, Ohio, United States

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Brussels, , Belgium

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Charleroi, , Belgium

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Edegem, , Belgium

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Leuven, , Belgium

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Liège, , Belgium

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Liège, , Belgium

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Belo Horizonte, , Brazil

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Ijuí, , Brazil

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Porto Alegre, , Brazil

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Rio de Janeiro, , Brazil

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Santo André, , Brazil

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São Paulo, , Brazil

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São Paulo, , Brazil

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São Paulo, , Brazil

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Plovdiv, , Bulgaria

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Sofia, , Bulgaria

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Sofia, , Bulgaria

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Sofia, , Bulgaria

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Sofia, , Bulgaria

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Varna, , Bulgaria

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Oshawa, Ontario, Canada

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Ottawa, Ontario, Canada

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Toronto, Ontario, Canada

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Ostrava, , Czechia

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Prague, , Czechia

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Znojmo, , Czechia

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Brest, , France

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Clermont-Ferrand, , France

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Dijon, , France

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Lyon, , France

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Marseille, , France

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Rennes, , France

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Budapest, , Hungary

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Budapest, , Hungary

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Budapest, , Hungary

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Budapest, , Hungary

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Győr, , Hungary

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Mosdós, , Hungary

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Székesfehérvár, , Hungary

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Törökbálint, , Hungary

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Bologna, , Italy

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Genova, , Italy

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Milan, , Italy

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Orbassano, , Italy

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Perugia, , Italy

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Roma, , Italy

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Rozzano, , Italy

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México, , Mexico

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Morelia, , Mexico

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Zacatecas City, , Mexico

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Lima, , Peru

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Lima, , Peru

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Lima, , Peru

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Lima, , Peru

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A Coruña, , Spain

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Badalona(Barcelona), , Spain

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Barcelona, , Spain

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Madrid, , Spain

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Málaga, , Spain

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Countries

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United States Belgium Brazil Bulgaria Canada Czechia France Hungary Italy Mexico Peru Spain

References

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Janne PA, Smith I, McWalter G, Mann H, Dougherty B, Walker J, Orr MC, Hodgson DR, Shaw AT, Pereira JR, Jeannin G, Vansteenkiste J, Barrios CH, Franke FA, Crino L, Smith P. Impact of KRAS codon subtypes from a randomised phase II trial of selumetinib plus docetaxel in KRAS mutant advanced non-small-cell lung cancer. Br J Cancer. 2015 Jul 14;113(2):199-203. doi: 10.1038/bjc.2015.215. Epub 2015 Jun 30.

Reference Type DERIVED
PMID: 26125448 (View on PubMed)

Janne PA, Shaw AT, Pereira JR, Jeannin G, Vansteenkiste J, Barrios C, Franke FA, Grinsted L, Zazulina V, Smith P, Smith I, Crino L. Selumetinib plus docetaxel for KRAS-mutant advanced non-small-cell lung cancer: a randomised, multicentre, placebo-controlled, phase 2 study. Lancet Oncol. 2013 Jan;14(1):38-47. doi: 10.1016/S1470-2045(12)70489-8. Epub 2012 Nov 28.

Reference Type DERIVED
PMID: 23200175 (View on PubMed)

Related Links

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https://cancerstudylocator.com/azo/home

Cancer Study Locator (For US and Canada sites only)

Other Identifiers

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D1532C00016

Identifier Type: -

Identifier Source: org_study_id

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