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

• Sponsor: AstraZeneca (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00890825
• Collaborator: (none)
• Enrollment: 88
• Locations: 64
• Arms: 2
• Actual Duration (Months): 90.4
• Patients Per Site: 1.4
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Non Small Cell Lung Cancer	Drug: AZD6244; Drug: docetaxel; Drug: Placebo	Phase 2

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

• Study Type: Interventional
• Actual Enrollment: 88 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: Apr 20, 2009
• Actual Primary Completion Date: May 11, 2011
• Actual Study Completion Date: Nov 2, 2016

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: AZD6244 + Docetaxel AZD6244 75 mg bd + Docetaxel 75 mg/m^2	Drug: AZD6244; oral capsules, 75mg twice daily; Other Names: Selumetinib ; Drug: docetaxel; 75mg/m2 iv on day 1 of every 21 day cycle; Other Names: Taxotere
Placebo Comparator: Placebo + Docetaxel Placebo + Docetaxel 75 mg/m^2	Drug: docetaxel; 75mg/m2 iv on day 1 of every 21 day cycle; Other Names: Taxotere ; Drug: Placebo; placebo

Outcome Measures

Primary Outcome Measures

1. Overall Survival [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.

Secondary Outcome Measures

1. Progression Free Survival [At least 12 months after start of treatment]

   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.

2. Objective Response Rate [At least 12 months after start of treatment]

   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.

3. Duration of Response [At least 12 months after start of treatment]

   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.

4. Change From Baseline in Tumour Size at 6 Week. [6 weeks after first dose of treatment]

   Percentage change from baseline in tumour size at 6 week. Values calculated as tumour sizes at 6 weeks minus value at baseline.

5. Change From Baseline in Tumour Size at Week 12 [12 weeks]

   Percentage change from baseline in tumour size at Week 12. Values calculated as tumour sizes at 12 weeks minus value at baseline.

6. Alive and Progression-Free at 6 Months [6 months after first dose of treatment]

   Percentage of patients alive and progression-free at 6 months

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 130 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Site	Los Angeles	California	United States	90095
2	Research Site	Aurora	Colorado	United States	80045
3	Research Site	Boston	Massachusetts	United States	02115
4	Research Site	Columbus	Ohio	United States	43210
5	Research Site	Brussels		Belgium	1090
6	Research Site	Charleroi		Belgium	6000
7	Research Site	Edegem		Belgium	2650
8	Research Site	Leuven		Belgium	3000
9	Research Site	Liege		Belgium	B-4000
10	Research Site	Liège		Belgium	4000
11	Research Site	Belo Horizonte		Brazil	30180-090
12	Research Site	Ijuí		Brazil	98700-000
13	Research Site	Porto Alegre		Brazil	90610-000
14	Research Site	Rio de Janeiro		Brazil	20230-130
15	Research Site	Santo André		Brazil	09060-650
16	Research Site	Sao Paulo		Brazil	01221-020
17	Research Site	Sao Paulo		Brazil	04023-062
18	Research Site	Sao Paulo		Brazil	04530-001
19	Research Site	Plovdiv		Bulgaria	4000
20	Research Site	Sofia		Bulgaria	1233
21	Research Site	Sofia		Bulgaria	1527
22	Research Site	Sofia		Bulgaria	1756
23	Research Site	Sofia		Bulgaria	1784
24	Research Site	Varna		Bulgaria	9010
25	Research Site	Oshawa	Ontario	Canada	L1G 2B9
26	Research Site	Ottawa	Ontario	Canada	K1H 8L6
27	Research Site	Toronto	Ontario	Canada	M5G 2M9
28	Research Site	Ostrava		Czechia	708 52
29	Research Site	Praha 8		Czechia	180 81
30	Research Site	Znojmo		Czechia	669 02
31	Research Site	Brest Cedex		France	29609
32	Research Site	Clermont Ferrand		France	63003
33	Research Site	Dijon		France	21034
34	Research Site	Lyon Cedex 08		France	69373
35	Research Site	Marseille		France	13015
36	Research Site	Rennes Cedex 9		France	35033
37	Research Site	Budapest		Hungary	1032
38	Research Site	Budapest		Hungary	1121
39	Research Site	Budapest		Hungary	1122
40	Research Site	Budapest		Hungary	1125
41	Research Site	Györ		Hungary	9024
42	Research Site	Mosdós		Hungary	7257
43	Research Site	Székesfehérvár		Hungary	8000
44	Research Site	Törökbálint		Hungary	2045
45	Research Site	Bologna		Italy	40131
46	Research Site	Genova		Italy	16100
47	Research Site	Milano		Italy	20162
48	Research Site	Orbassano		Italy	10043
49	Research Site	Perugia		Italy	06132
50	Research Site	Roma		Italy	00144
51	Research Site	Rozzano		Italy	20089
52	Research Site	Mexico		Mexico	14080
53	Research Site	Morelia		Mexico	58000
54	Research Site	Zacatecas		Mexico	98000
55	Research Site	Lima		Peru	LIMA 11
56	Research Site	Lima		Peru	LIMA 27
57	Research Site	Lima		Peru	LIMA 33
58	Research Site	Lima		Peru	LIMA 41
59	Research Site	A Coruña		Spain	15006
60	Research Site	Badalona(Barcelona)		Spain	08916
61	Research Site	Barcelona		Spain	08028
62	Research Site	Madrid		Spain	28041
63	Research Site	Malaga		Spain	29010
64	Research Site	Málaga		Spain	29010

Sponsors and Collaborators

• AstraZeneca

Investigators

• Principal Investigator: Dr. Pasi Janne, Dana-Farber Cancer Institute, Boston, USA
• Study Director: Dr. Gabriella Mariani, AstraZeneca, Hertfordshire, UK

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

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

Publications

None provided.

• Responsible Party: AstraZeneca
• ClinicalTrials.gov Identifier: NCT00890825
• Other Study ID Numbers: D1532C00016
• First Posted: Apr 30, 2009
• Last Update Posted: Jun 20, 2018
• Last Verified: May 1, 2018

• Keywords provided by AstraZeneca: Non small cell lung cancer (NSCLC); KRAS mutation
• Additional relevant MeSH terms: Carcinoma, Non-Small-Cell Lung; Docetaxel

Study Results

Participant Flow

Recruitment Details	Selection of patients was in 2nd line patients with KRAS mutation positive locally advanced or metastatic NSCLC (Stage IIIB - IV).First patient enrolled: 20 April 2009.Last patient last visit: 30 June 2010.Data Cut Off (DCO): 01 May 2011

Arm/Group Title	AZD6244 + Docetaxel	Placebo + Docetaxel
Arm/Group Description	AZD6244 75 mg bd + Docetaxel 75 mg/m^2	Placebo + Docetaxel 75 mg/m^2
Period Title: Overall Study
STARTED	44	43
COMPLETED	30	29
NOT COMPLETED	14	14

Baseline Characteristics

Arm/Group Title	AZD6244 + Docetaxel	Placebo + Docetaxel	Total
Arm/Group Description	AZD6244 75 mg bd + Docetaxel 75 mg/m^2	Placebo + Docetaxel 75 mg/m^2	Total of all reporting groups
Overall Participants	44	43	87
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	58.2 (9.22)	58.6 (8.38)	58.4 (8.77)
Age, Customized (Count of Participants)
Age group : <=55 years	15 34.1%	15 34.9%	30 34.5%
Age group : >55 years	29 65.9%	28 65.1%	57 65.5%
Sex: Female, Male (Count of Participants)
Female	23 52.3%	23 53.5%	46 52.9%
Male	21 47.7%	20 46.5%	41 47.1%
Race/Ethnicity, Customized (Count of Participants)
White	41 93.2%	40 93%	81 93.1%
Black or African American	1 2.3%	1 2.3%	2 2.3%
Other	2 4.5%	2 4.7%	4 4.6%
Race/Ethnicity, Customized (Count of Participants)
Hispanic or Latino	7 15.9%	10 23.3%	17 19.5%
Not Hispanic or Latino	37 84.1%	33 76.7%	70 80.5%

Outcome Measures

1. Primary Outcome

Title	Overall Survival
Description	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.
Time Frame	At least 12 months since start of treatment.

Outcome Measure Data

Analysis Population Description

MITT

Arm/Group Title	AZD6244 + Docetaxel	Placebo + Docetaxel
Arm/Group Description	AZD6244 75 mg bd + Docetaxel 75 mg/m^2	Placebo + Docetaxel 75 mg/m^2
Measure Participants	43	40
Died	29 65.9%	27 62.8%
Alive at DCO	13 29.5%	13 30.2%
Withdrawn	1 2.3%	0 0%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	AZD6244 + Docetaxel, Placebo + Docetaxel
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.2069
	Comments	One-sided p-value. The p-value is associated with the point estimate (e.g. HR comparing AZD6244 + Docetaxel vs Placebo + Docetaxel) on the outcome measure - Overall survival.
	Method	Regression, Cox
	Comments	Analysis adjusted for the following covariates; WHO PS, gender, histology and smoking status
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.80
	Confidence Interval	(2-Sided) 80%; 0.56 to 1.14
	Parameter Dispersion	Type: Value:
	Estimation Comments	A Hazard Ratio less than 1 favoured AZD6244 + Docetaxel

2. Secondary Outcome

Title	Progression Free Survival
Description	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.
Time Frame	At least 12 months after start of treatment

Outcome Measure Data

Analysis Population Description

MITT

Arm/Group Title	AZD6244 + Docetaxel	Placebo + Docetaxel
Arm/Group Description	AZD6244 75 mg bd + Docetaxel 75 mg/m^2	Placebo + Docetaxel 75 mg/m^2
Measure Participants	43	40
Progression	35 79.5%	36 83.7%
Prog. after >2 missed or non-eval. assessments	1 2.3%	2 4.7%
No progression	7 15.9%	2 4.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	AZD6244 + Docetaxel, Placebo + Docetaxel
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0138
	Comments	One-sided p-value. The p-value is associated with the point estimate (e.g. HR comparing AZD6244 + Docetaxel vs Placebo + Docetaxel) on the outcome measure.
	Method	Regression, Cox
	Comments	The model allowed for the effect of treatment and included terms for WHO PS, gender, histology, and smoking status.
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.58
	Confidence Interval	(2-Sided) 80%; 0.42 to 0.79
	Parameter Dispersion	Type: Value:
	Estimation Comments	A Hazard Ratio (HR) < 1 favoured AZD6244 + Docetaxel

3. Secondary Outcome

Title	Objective Response Rate
Description	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.
Time Frame	At least 12 months after start of treatment

Outcome Measure Data

Analysis Population Description

MITT

Arm/Group Title	AZD6244 + Docetaxel	Placebo + Docetaxel
Arm/Group Description	AZD6244 75 mg bd + Docetaxel 75 mg/m^2	Placebo + Docetaxel 75 mg/m^2
Measure Participants	43	40
Response	16 36.4%	0 0%
No response	27 61.4%	40 93%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	AZD6244 + Docetaxel, Placebo + Docetaxel
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments	Two-sided P-value
	Method	Fisher Exact
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	37.2
	Confidence Interval	(2-Sided) 95%; 23 to 53
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Duration of Response
Description	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.
Time Frame	At least 12 months after start of treatment

Outcome Measure Data

Analysis Population Description

MITT

Arm/Group Title	AZD6244 + Docetaxel	Placebo + Docetaxel
Arm/Group Description	AZD6244 75 mg bd + Docetaxel 75 mg/m^2	Placebo + Docetaxel 75 mg/m^2
Measure Participants	43	40
Mean (Standard Error) [Days]	193.4 (0.207)	NA (NA)

5. Secondary Outcome

Title	Change From Baseline in Tumour Size at 6 Week.
Description	Percentage change from baseline in tumour size at 6 week. Values calculated as tumour sizes at 6 weeks minus value at baseline.
Time Frame	6 weeks after first dose of treatment

Outcome Measure Data

Analysis Population Description

MITT

Arm/Group Title	AZD6244 + Docetaxel	Placebo + Docetaxel
Arm/Group Description	AZD6244 75 mg bd + Docetaxel 75 mg/m^2	Placebo + Docetaxel 75 mg/m^2
Measure Participants	43	40
Least Squares Mean (80% Confidence Interval) [Percentage change from baseline]	-16.98	0.05

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	AZD6244 + Docetaxel, Placebo + Docetaxel
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.004
	Comments	One-sided p-value. The p-value is associated with the point estimate comparing AZD6244 + Docetaxel vs Placebo + Docetaxel on the outcome measure.
	Method	ANCOVA
	Comments	LS means were adjusted for baseline tumour size, time from baseline scan to randomisation, WHO PS, gender, histology, and smoking status.
Method of Estimation	Estimation Parameter	LSmeans difference
	Estimated Value	-17.03
	Confidence Interval	(2-Sided) 80%; -25.2 to -8.86
	Parameter Dispersion	Type: Value:
	Estimation Comments	(AZD6244 + Docetaxel) - (Placebo + Docetaxel)

6. Secondary Outcome

Title	Change From Baseline in Tumour Size at Week 12
Description	Percentage change from baseline in tumour size at Week 12. Values calculated as tumour sizes at 12 weeks minus value at baseline.
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

MITT

Arm/Group Title	AZD6244 + Docetaxel	Placebo + Docetaxel
Arm/Group Description	AZD6244 75 mg bd + Docetaxel 75 mg/m^2	Placebo + Docetaxel 75 mg/m^2
Measure Participants	43	40
Least Squares Mean (80% Confidence Interval) [Percent change from baseline]	-19.38	6.62

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	AZD6244 + Docetaxel, Placebo + Docetaxel
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.004
	Comments	One-sided p-value. The p-value is associated with the point estimate comparing AZD6244 + Docetaxel vs Placebo + Docetaxel on the outcome measure.
	Method	ANCOVA
	Comments	LS means were adjusted for baseline tumour size, time from baseline scan to randomisation, WHO PS, gender, histology, and smoking status
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-26.0
	Confidence Interval	(2-Sided) 80%; -38.34 to -13.7
	Parameter Dispersion	Type: Value:
	Estimation Comments	(AZD6244 + Docetaxel) - (Placebo + Docetaxel)

7. Secondary Outcome

Title	Alive and Progression-Free at 6 Months
Description	Percentage of patients alive and progression-free at 6 months
Time Frame	6 months after first dose of treatment

Outcome Measure Data

Analysis Population Description

MITT

Arm/Group Title	AZD6244 + Docetaxel	Placebo + Docetaxel
Arm/Group Description	AZD6244 75 mg bd + Docetaxel 75 mg/m^2	Placebo + Docetaxel 75 mg/m^2
Measure Participants	43	40
Number [percentage]	37.1	15.8

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	AZD6244 + Docetaxel, Placebo + Docetaxel
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0158
	Comments	One-sided p-value. The p-value is associated with the point estimate (e.g. HR comparing AZD6244 + Docetaxel vs Placebo + Docetaxel) on the outcome measure.
	Method	Log Rank
	Comments	Confidence interval (CI) used Greenwood's formula for the standard error of a survival estimate
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.54
	Confidence Interval	(2-Sided) 80%; 0.37 to 0.78
	Parameter Dispersion	Type: Value:
	Estimation Comments	A hazard ratio (HR) <1 favours AZD6244 75 mg bd+Docetaxel

Adverse Events

Time Frame	Over a minimum period of 12 months since start of treatment, or the date of the final analysis of the data, whichever is the later
Arm/Group Title	AZD6244 + Docetaxel		Placebo + Docetaxel
Arm/Group Description	AZD6244 75 mg bd + Docetaxel 75 mg/m^2		Placebo + Docetaxel 75 mg/m^2
All Cause Mortality
	AZD6244 + Docetaxel		Placebo + Docetaxel
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	AZD6244 + Docetaxel		Placebo + Docetaxel
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	26/44 (59.1%)		13/42 (31%)
Blood and lymphatic system disorders
Febrile neutropena	6/44 (13.6%)	6	0/42 (0%)	0
Neutropena	3/44 (6.8%)	3	3/42 (7.1%)	3
Cardiac disorders
Acute coronary syndrome	1/44 (2.3%)	1	0/42 (0%)	0
Atrial flutter	0/44 (0%)	0	1/42 (2.4%)	1
Cardiac arrest	0/44 (0%)	0	1/42 (2.4%)	1
Pericardial effusion	1/44 (2.3%)	1	0/42 (0%)	0
Sinus bradycardia	1/44 (2.3%)	1	0/42 (0%)	0
Gastrointestinal disorders
Vomiting	1/44 (2.3%)	1	1/42 (2.4%)	1
Abdominal pain	1/44 (2.3%)	1	0/42 (0%)	0
Colitis	1/44 (2.3%)	1	0/42 (0%)	0
Dyspepsia	0/44 (0%)	0	1/42 (2.4%)	1
Gastric ulcer haemorrhage	1/44 (2.3%)	1	0/42 (0%)	0
Retroperitoneal haematoma	1/44 (2.3%)	1	0/42 (0%)	0
General disorders
Face oedema	2/44 (4.5%)	2	0/42 (0%)	0
Pyrexia	1/44 (2.3%)	1	0/42 (0%)	0
Immune system disorders
Drug hypersensitivity	1/44 (2.3%)	1	0/42 (0%)	0
Infections and infestations
Pneumonia	4/44 (9.1%)	4	0/42 (0%)	0
Lower respiratory tract infection bacterial	1/44 (2.3%)	1	1/42 (2.4%)	1
Cystitis	0/44 (0%)	0	1/42 (2.4%)	1
Empyema	1/44 (2.3%)	1	0/42 (0%)	0
Influenza	0/44 (0%)	0	1/42 (2.4%)	1
Neutropenic infection	1/44 (2.3%)	1	0/42 (0%)	0
Respiratory tract infection viral	0/44 (0%)	0	1/42 (2.4%)	1
Sepsis	1/44 (2.3%)	1	0/42 (0%)	0
Urinary tract infection	1/44 (2.3%)	1	0/42 (0%)	0
Investigations
Blood creatine phosphokinase increased	1/44 (2.3%)	1	0/42 (0%)	0
Creatinine renal clearance decreased	1/44 (2.3%)	1	0/42 (0%)	0
Electrocardiogram t wave inversion	1/44 (2.3%)	1	0/42 (0%)	0
Neutrophil count decreased	1/44 (2.3%)	1	0/42 (0%)	0
Metabolism and nutrition disorders
Decreased appetite	0/44 (0%)	0	1/42 (2.4%)	1
Musculoskeletal and connective tissue disorders
Back pain	0/44 (0%)	0	2/42 (4.8%)	2
Pain in extremity	0/44 (0%)	0	1/42 (2.4%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumour necrosis	1/44 (2.3%)	1	0/42 (0%)	0
Tumour pain	1/44 (2.3%)	1	0/42 (0%)	0
Nervous system disorders
Syncope	1/44 (2.3%)	1	0/42 (0%)	0
Respiratory, thoracic and mediastinal disorders
Respiratory failure	3/44 (6.8%)	3	2/42 (4.8%)	2
Interstitial lung disease	2/44 (4.5%)	2	0/42 (0%)	0
Pulmonary embolism	2/44 (4.5%)	2	0/42 (0%)	0
Dyspnoea	0/44 (0%)	0	1/42 (2.4%)	1
Dyspnoea exertional	1/44 (2.3%)	1	0/42 (0%)	0
Pneumonitis	0/44 (0%)	0	1/42 (2.4%)	1
Pneumothorax	1/44 (2.3%)	1	0/42 (0%)	0
Pulmonary haemorrhage	1/44 (2.3%)	1	0/42 (0%)	0
Skin and subcutaneous tissue disorders
Dermatitis acneiform	1/44 (2.3%)	1	0/42 (0%)	0
Psoriasis	1/44 (2.3%)	1	0/42 (0%)	0
Other (Not Including Serious) Adverse Events
	AZD6244 + Docetaxel		Placebo + Docetaxel
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	43/44 (97.7%)		42/42 (100%)
Blood and lymphatic system disorders
Neutropenia	17/44 (38.6%)	17	15/42 (35.7%)	15
Anaemia	7/44 (15.9%)	7	5/42 (11.9%)	5
Febrile neutropenia	7/44 (15.9%)	7	0/42 (0%)	0
Eye disorders
Vision blurred	6/44 (13.6%)	6	1/42 (2.4%)	1
Gastrointestinal disorders
Diarrhoea	32/44 (72.7%)	32	7/42 (16.7%)	7
Nausea	19/44 (43.2%)	19	12/42 (28.6%)	12
Vomiting	19/44 (43.2%)	19	9/42 (21.4%)	9
Stomatitis	16/44 (36.4%)	16	8/42 (19%)	8
Constipation	14/44 (31.8%)	14	8/42 (19%)	8
Abdominal pain upper	8/44 (18.2%)	8	4/42 (9.5%)	4
Dyspepsia	8/44 (18.2%)	8	4/42 (9.5%)	4
Abdominal pain	8/44 (18.2%)	8	1/42 (2.4%)	1
General disorders
Fatigue	12/44 (27.3%)	12	14/42 (33.3%)	14
Asthenia	31/44 (70.5%)	31	28/42 (66.7%)	28
Oedema peripheral	18/44 (40.9%)	18	7/42 (16.7%)	7
Pyrexia	12/44 (27.3%)	12	5/42 (11.9%)	5
Metabolism and nutrition disorders
Decreased appetite	15/44 (34.1%)	15	11/42 (26.2%)	11
Dehydration	5/44 (11.4%)	5	1/42 (2.4%)	1
Musculoskeletal and connective tissue disorders
Myalgia	6/44 (13.6%)	6	7/42 (16.7%)	7
Musculoskeletal chest pain	3/44 (6.8%)	3	8/42 (19%)	8
Arthralgia	2/44 (4.5%)	2	8/42 (19%)	8
Back pain	2/44 (4.5%)	2	6/42 (14.3%)	6
Nervous system disorders
Headache	6/44 (13.6%)	6	5/42 (11.9%)	5
Dysgeusia	5/44 (11.4%)	5	2/42 (4.8%)	2
Neuropathy peripheral	5/44 (11.4%)	5	1/42 (2.4%)	1
Respiratory, thoracic and mediastinal disorders
Cough	10/44 (22.7%)	10	8/42 (19%)	8
Dysonoea exertional	8/44 (18.2%)	8	10/42 (23.8%)	10
Dyspnoea	5/44 (11.4%)	5	10/42 (23.8%)	10
Epistaxis	7/44 (15.9%)	7	2/42 (4.8%)	2
Skin and subcutaneous tissue disorders
Alopecia	13/44 (29.5%)	13	9/42 (21.4%)	9
Dermatitis acneiform	17/44 (38.6%)	17	2/42 (4.8%)	2
Dry skin	10/44 (22.7%)	10	4/42 (9.5%)	4

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.