Non Small Cell Lung CancerPhase 2NCT00890825
AZD6244 in Combination With Docetaxel Versus Docetaxel Alone in KRAS Mutation Positive NSCLC Patients
A Phase 2 study testing AZD6244 and docetaxel in people with Non Small Cell Lung Cancer, run by AstraZeneca at 63 sites in 12 countries.
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. Read more about this study
- Who is it for?
- Ages 18 to 130 years
- Conditions the study is for
- Non Small Cell Lung Cancer
- What is being tested?
- AZD6244 and docetaxel
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 88 participants
- Where
- 63 sitesin 12 countries
- Study dates
- 20 Apr 2009to 2 Nov 2016
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 130 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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).
Who cannot join
- 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
Trial locations and contacts
63 sites in 12 countries.
63 sites in 12 countries
Brazil8 sites
Research Site
Belo Horizonte, 30180-090
Research Site
Ijuí, 98700-000
Research Site
Porto Alegre, 90610-000
Research Site
Rio de Janeiro, 20230-130
Research Site
Santo André, 09060-650
Research Site
São Paulo, 01221-020
Research Site
São Paulo, 04023-062
Research Site
São Paulo, 04530-001
Hungary8 sites
Research Site
Budapest, 1032
Research Site
Budapest, 1121
Research Site
Budapest, 1122
Research Site
Budapest, 1125
Research Site
Győr, 9024
Research Site
Mosdós, 7257
Research Site
Székesfehérvár, 8000
Research Site
Törökbálint, 2045
Italy7 sites
Research Site
Bologna, 40131
Research Site
Genova, 16100
Research Site
Milan, 20162
Research Site
Orbassano, 10043
Research Site
Perugia, 06132
Research Site
Roma, 00144
Research Site
Rozzano, 20089
Belgium6 sites
Research Site
Brussels, 1090
Research Site
Charleroi, 6000
Research Site
Edegem, 2650
Research Site
Leuven, 3000
Research Site
Liège, 4000
Research Site
Liège, B-4000
Bulgaria6 sites
Research Site
Plovdiv, 4000
Research Site
Sofia, 1233
Research Site
Sofia, 1527
Research Site
Sofia, 1756
Research Site
Sofia, 1784
Research Site
Varna, 9010
France6 sites
Research Site
Brest, 29609
Research Site
Clermont-Ferrand, 63003
Research Site
Dijon, 21034
Research Site
Lyon, 69373
Research Site
Marseille, 13015
Research Site
Rennes, 35033
Spain5 sites
Research Site
A Coruña, 15006
Research Site
Badalona(Barcelona), 08916
Research Site
Barcelona, 08028
Research Site
Madrid, 28041
Research Site
Málaga, 29010
United States4 sites
Research Site
Aurora, Colorado, 80045
Research Site
Boston, Massachusetts, 02115
Research Site
Columbus, Ohio, 43210
Research Site
Los Angeles, California, 90095
Peru4 sites
Research Site
Lima, LIMA 11
Research Site
Lima, LIMA 27
Research Site
Lima, LIMA 33
Research Site
Lima, LIMA 41
Canada3 sites
Research Site
Oshawa, Ontario, L1G 2B9
Research Site
Ottawa, Ontario, K1H 8L6
Research Site
Toronto, Ontario, M5G 2M9
Czechia3 sites
Research Site
Ostrava, 708 52
Research Site
Prague, 180 81
Research Site
Znojmo, 669 02
Mexico3 sites
Research Site
México, 14080
Research Site
Morelia, 58000
Research Site
Zacatecas City, 98000
About this study
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
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.
Read the detailed 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).
- Conditions
- Non Small Cell Lung Cancer
- Being tested
- AZD6244, docetaxel, Placebo
- Keywords
- Non small cell lung cancer (NSCLC), KRAS mutation
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AZD6244Drug
Also called Selumetinib
oral capsules, 75mg twice daily
docetaxelDrug
Also called Taxotere
75mg/m2 iv on day 1 of every 21 day cycle
PlaceboDrug
placebo
| Study group | Role | What they receive |
|---|---|---|
| AZD6244 + Docetaxel | Active comparator | AZD6244 75 mg bd + Docetaxel 75 mg/m^2 Receives: Drug: AZD6244; Drug: docetaxel |
| Placebo + Docetaxel | Placebo comparator | Placebo + Docetaxel 75 mg/m^2 Receives: Drug: docetaxel; Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: At least 12 months since start of treatment.
Secondary outcomes (6)
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.
Measured: At least 12 months after start of treatment
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.
Measured: At least 12 months after start of treatment
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.
Measured: At least 12 months after start of treatment
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.
Measured: 6 weeks after first dose of treatment
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.
Measured: 12 weeks
Alive and Progression-Free at 6 Months
Percentage of patients alive and progression-free at 6 months
Measured: 6 months after first dose of treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Apr 2009 (estimated)
- Study start20 Apr 2009
- Primary completion11 May 2011
- Study completion2 Nov 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Non Small Cell Lung CancerStudies of the same condition, open and under way.
- More trials run by AstraZenecaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 88 participants (actual)
Sponsor and investigators
- Lead sponsor
- AstraZeneca
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Dr. Pasi Janne, Principal investigator, Dana-Farber Cancer Institute, Boston, USADr. Gabriella Mariani, Study director, AstraZeneca, Hertfordshire, UK
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00890825
- Sponsor's protocol ID
- D1532C00016
- Status last verified
- May 2018
- First submitted
- 29 Apr 2009
- Last updated
- 20 Jun 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
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.
PubMed 26125448Janne 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.
PubMed 23200175
Study at a glance
From the registry record, last updated by the sponsor on 20 Jun 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00890825
- Acronym / sponsor ID
- D1532C00016
- Conditions
- Non Small Cell Lung Cancer
- Keywords
- Non small cell lung cancer (NSCLC), KRAS mutation
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 88 participants (actual)
- Lead sponsor
- AstraZenecaIndustry (pharma, biotech, devices)
- Study start
- 20 Apr 2009 (actual)
- Primary completion
- 11 May 2011 (actual)
- Study completion
- 2 Nov 2016 (actual)
- First posted
- 30 Apr 2009 (estimated)
- Results
- Posted 20 Jun 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| AZD6244 + Docetaxel | Active comparator | Drug: AZD6244, Drug: docetaxelAZD6244 75 mg bd + Docetaxel 75 mg/m^2 |
| Placebo + Docetaxel | Placebo comparator | Drug: docetaxel, Drug: PlaceboPlacebo + Docetaxel 75 mg/m^2 |
Who may qualify
- Ages
- 18 to 130 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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).
Key exclusion criteria (4 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AZD6244Also: Selumetiniboral capsules, 75mg twice daily | Drug | AZD6244 + Docetaxel |
| docetaxelAlso: Taxotere75mg/m2 iv on day 1 of every 21 day cycle | Drug | AZD6244 + Docetaxel, Placebo + Docetaxel |
| Placeboplacebo | Drug | Placebo + Docetaxel |
Primary outcome
Overall Survival
Time frame: At least 12 months since start of treatment.
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.
6 secondary outcomes
Progression Free Survival
Time frame: At least 12 months after start of treatment
Objective Response Rate
Time frame: At least 12 months after start of treatment
Duration of Response
Time frame: At least 12 months after start of treatment
Change From Baseline in Tumour Size at 6 Week.
Time frame: 6 weeks after first dose of treatment
Change From Baseline in Tumour Size at Week 12
Time frame: 12 weeks
Alive and Progression-Free at 6 Months
Time frame: 6 months after first dose of treatment
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Jun 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 26125448Janne 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.
- Derived from this study: PubMed 23200175Janne 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.
- Cancer Study Locator (For US and Canada sites only)Link provided by the sponsor.
Related trials for Non Small Cell Lung Cancer
RecruitingPhase 1/2
Study of INBRX-106 and INBRX-106 in Combination With Pembrolizumab (Keytruda®) in Subjects With Locally Advanced or Metastatic Solid Tumors (Hexavalent OX40 Agonist)
Solid Tumor, Non-Small Cell Lung Cancer
RecruitingObservational study
A Prospective ,Multicenter ,Non-interventional ,Real-world Study Observing Changes in Molecular Markers Osimertinib Targeted Therapy in EGFRm NSCLC
Non Small Cell Lung Cancer
RecruitingPhase 3
A Study Evaluating Sotorasib Platinum Doublet Combination Versus Pembrolizumab Platinum Doublet Combination as a Front-Line Therapy in Participants With Stage IV or Advanced Stage IIIB/C Nonsquamous Non-Small Cell Lung Cancers (CodeBreaK 202)
Non-Small Cell Lung Cancer (NSCLC)
Active, not recruitingPhase 2
Datopotamab Deruxtecan (Dato-DXd, DS-1062a) in Advanced and/or Unresectable Non-Small Cell Lung Cancer
Metastatic Lung Cancer, Advanced Non Small Cell Lung Cancer
Not yet recruitingPhase 1/2
STAR0602 With Nivolumab in Non Small Cell Lung Cancer and in Metastatic Castrate-Resistant Prostate Cancer, and STAR0602 Alone in Thymic Carcinoma
NSCLC, Non-Small Cell Lung Cancer
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Dr. Pasi Janne principal investigator
Dana-Farber Cancer Institute, Boston, USA
Dr. Gabriella Mariani study director
AstraZeneca, Hertfordshire, UK
63 sites in 12 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing AZD6244 and docetaxel in people with Non Small Cell Lung Cancer, run by AstraZeneca at 63 sites in 12 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 20 Jun 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 63 sites in Brazil, Hungary, Italy, Belgium, Bulgaria and 7 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 20 Jun 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall Survival (time frame: At least 12 months since start of treatment.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00890825, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Jun 2018.