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

Non Small Cell Lung Cancer Clinical Trial

Official title:

Phase II, Double-Blind, Randomised, Placebo-Controlled Study to Assess the Efficacy of AZD6244 in Combination With Docetaxel, Compared With Docetaxel Alone, in 2nd Line Patients With KRAS Mutation Positive Locally Advanced Metastatic NSCLC

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00890825
• Other study ID #: D1532C00016
• Status: Completed
• Phase: Phase 2
• Start date: April 20, 2009
• Est. completion date: November 2, 2016

Study information

• Verified date: May 2018
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 88
• Est. completion date: November 2, 2016
• Est. primary completion date: May 11, 2011
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 130 Years

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Non Small Cell Lung Cancer

Intervention

Drug:
• AZD6244
oral capsules, 75mg twice daily
• docetaxel
75mg/m2 iv on day 1 of every 21 day cycle
• Placebo
placebo

Locations

Country	Name	City	State
Belgium	Research Site	Brussels
Belgium	Research Site	Charleroi
Belgium	Research Site	Edegem
Belgium	Research Site	Leuven
Belgium	Research Site	Liege
Belgium	Research Site	Liège
Brazil	Research Site	Belo Horizonte
Brazil	Research Site	Ijuí
Brazil	Research Site	Porto Alegre
Brazil	Research Site	Rio de Janeiro
Brazil	Research Site	Santo André
Brazil	Research Site	Sao Paulo
Brazil	Research Site	Sao Paulo
Brazil	Research Site	Sao Paulo
Bulgaria	Research Site	Plovdiv
Bulgaria	Research Site	Sofia
Bulgaria	Research Site	Sofia
Bulgaria	Research Site	Sofia
Bulgaria	Research Site	Sofia
Bulgaria	Research Site	Varna
Canada	Research Site	Oshawa	Ontario
Canada	Research Site	Ottawa	Ontario
Canada	Research Site	Toronto	Ontario
Czechia	Research Site	Ostrava
Czechia	Research Site	Praha 8
Czechia	Research Site	Znojmo
France	Research Site	Brest Cedex
France	Research Site	Clermont Ferrand
France	Research Site	Dijon
France	Research Site	Lyon Cedex 08
France	Research Site	Marseille
France	Research Site	Rennes Cedex 9
Hungary	Research Site	Budapest
Hungary	Research Site	Budapest
Hungary	Research Site	Budapest
Hungary	Research Site	Budapest
Hungary	Research Site	Györ
Hungary	Research Site	Mosdós
Hungary	Research Site	Székesfehérvár
Hungary	Research Site	Törökbálint
Italy	Research Site	Bologna
Italy	Research Site	Genova
Italy	Research Site	Milano
Italy	Research Site	Orbassano
Italy	Research Site	Perugia
Italy	Research Site	Roma
Italy	Research Site	Rozzano
Mexico	Research Site	Mexico
Mexico	Research Site	Morelia
Mexico	Research Site	Zacatecas
Peru	Research Site	Lima
Peru	Research Site	Lima
Peru	Research Site	Lima
Peru	Research Site	Lima
Spain	Research Site	A Coruña
Spain	Research Site	Badalona(Barcelona)
Spain	Research Site	Barcelona
Spain	Research Site	Madrid
Spain	Research Site	Malaga
Spain	Research Site	Málaga
United States	Research Site	Aurora	Colorado
United States	Research Site	Boston	Massachusetts
United States	Research Site	Columbus	Ohio
United States	Research Site	Los Angeles	California

Sponsors (1)

Lead Sponsor	Collaborator
AstraZeneca

Countries where clinical trial is conducted

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Survival	OS was calculated as the interval from the date of randomisation to the date of patient death (any cause). Patients who had not died at the time of the final analysis, or who withdrew consent, were censored at the last date the patient was known to be alive.	At least 12 months since start of treatment.
Secondary	Progression Free Survival	PFS was defined as the interval between the date of randomisation and the earlier date of objective disease progression per RECIST criteria or death due to any cause in the absence of progression. Patients who did not progress or die at the time of analysis were censored at the time of their latest evaluable objective tumour assessment. This also included patients who withdrew consent.	At least 12 months after start of treatment
Secondary	Objective Response Rate	ORR is defined as the ratio of proportions, patients with at least one visit response of CR or PR in AZD6244 + Docetaxel vs Placebo + Docetaxel.	At least 12 months after start of treatment
Secondary	Duration of Response	Duration of response is defined as the time from the date of first documented response until date of documented progression or death in the absence of disease progression, the end of response should coincide with the date of progression or death from any cause used for the PFS endpoint.	At least 12 months after start of treatment
Secondary	Change From Baseline in Tumour Size at 6 Week.	Percentage change from baseline in tumour size at 6 week. Values calculated as tumour sizes at 6 weeks minus value at baseline.	6 weeks after first dose of treatment
Secondary	Change From Baseline in Tumour Size at Week 12	Percentage change from baseline in tumour size at Week 12. Values calculated as tumour sizes at 12 weeks minus value at baseline.	12 weeks
Secondary	Alive and Progression-Free at 6 Months	Percentage of patients alive and progression-free at 6 months	6 months after first dose of treatment

External Links

•   Cancer Study Locator (For US and Canada sites only)