CompletedNCT01256359DOC-MEKUpdated Aug 15, 2024Results posted

Docetaxel With or Without AZD6244 in Melanoma

A Phase 2 interventional study of Docetaxel and AZD6244 and Docetaxel and placebo in Melanoma, sponsored by University of Oxford. Completed at 1 site in United Kingdom. Open to participants aged 16 Years and older. Per ClinicalTrials.gov, last updated 2024-08-15.

Sponsored by University of Oxford · Phase 2, Interventional, and Treatment

Phase: Phase 2
Study type: Interventional
Enrollment: 83
Allocation: Randomized
Ages: 16 Years and older
Sex: All

Study summary

This is a randomised, double-blind placebo controlled phase 2 trial. Patient will be randomly assigned 1:1 between 2 treatment arms. They will receive either docetaxel 75mg/m2 IV and placebo given bd, or AZD6244 75mg bd daily with docetaxel 75mg/m2 IV. Docetaxel will be administered every 3 weeks for a maximum 6 cycles, but AZD6244/placebo may be continued beyond this, until disease progression. The objective is to assess whether the combination of AZD6244 with docetaxel is worthy of evaluation in a definitive randomised study, with the null hypothesis being that the combination has activity similar to that of docetaxel alone in this population. After consent has been obtained mutational analysis of tumour BRAF will be performed on archival tumour tissue, where this information is not already known, to assess eligibility for the study. If there is no archival tissue a fresh biopsy will be requested from the patient. A blood sample will also be taken for future genetic analysis. Once taking part in the trial patients will need to attend their oncology unit regularly for monitoring and the delivery of treatment. Patients will undergo complete physical examination at screening, on C1D1, C1D8, C1D15, C2D1, C2D8 and day 1 of every subsequent cycle. Blood for haematology, biochemistry and clotting will be taken at each of these visits. A 12 lead ECG will be performed at screening . Disease assessment will be by CT scanning using modified RECIST criteria after 9 and 18 weeks, then every 3 months until disease progression.

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Conditions studied

Melanoma

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Melanoma 3,006

In context

Melanoma

3,006 studies on the registry are indexed under Melanoma; 520 are open to participants now.

This study's enrollment of 83 is above the median of 38 across 2,351 interventional studies indexed under Melanoma.

Browse Melanoma studies →

Lead sponsor

University of Oxford is the lead sponsor of 794 studies on the registry; 117 are open to participants now.

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 16 Years and older
Sexes eligible: All
Accepts healthy volunteers: No

Inclusion criteria

Aged >/= 16 years
Able to provide evidence from an accredited laboratory of wt BRAF status for their melanoma, or ascertainment of wt BRAF status from a sample of melanoma provided for mutational analysis in Oxford.
Unresectable stage 3 or 4, histologically proven cutaneous or unknown primary melanoma
At least 1 lesion, not previously irradiated, that can be accurately measured on CT or MRI as defined by modified RECIST criteria
ECOG performance score of 0 or 1.
Life expectancy of at least 12 weeks.
The patient is willing to give consent to the main study and able to comply with the protocol for the duration of the study, including scheduled follow-up visits and examinations.
Haematological and biochemical indices within the ranges shown below. Lab Test Value required Haemoglobin (Hb) >10g/dL White Blood Count (WBC) > 3x109/L Platelet count > 100,000/μL Absolute Neutrophil count > 1.5x109/L; Serum bilirubin ≤ 1.2 x ULN AST (SGOT) or ALT ≤ 2.5 x ULN LDH ≤ 2 x ULN Creatinine clearance (Cockcroft-Gault) >50 ml/min

Exclusion criteria

Exclusion Criteria:

Any anti-cancer therapy (including radiotherapy and participation in other clinical trials) within 28 days prior to Day 1.
Prior DNA damaging agents or cytotoxic chemotherapy for metastatic melanoma.
Any unresolved toxicity from prior anti-cancer therapy that is greater than CTCAE grade 2.
Pregnancy or breastfeeding women. Female patients must have a negative urinary or serum pregnancy test or have evidence of post-menopausal status (defined as absence of menstruation for > 12 months, bilateral oophrectomy or hysterectomy).
Grade ≥2 peripheral neuropathy at study entry.
Patients of reproductive potential who are not willing to use adequate contraceptive measures for the duration of the study (both male and female patients)
Known severe hypersensitivity reactions to docetaxel or other drugs formulated in polysorbate 80
Ocular or mucosal malignant melanoma
Another active malignancy within the past five years.
Evidence of brain metastases, unless surgically resected/stereotactic radiosurgery treated brain metastasis with no evidence of relapse on cerebral MRI, or treated brain metastasis and stable off treatment, including steroids, for 3 months.
Clinically significant and uncontrolled major medical condition(s): such as active infection, bleeding diathesis.
Patients who are known to be serologically positive for Hepatitis B, Hepatitis C or HIV.
Cardiac conditions, including uncontrolled hypertension (BP>160/100 despite treatment), heart failure NYHA class 2 or above, prior or current cardiomyopathy, myocardial infarction within 6 months or angina requiring nitrate therapy more than once a week.
Previous treatment with EGFR, ras, raf or MEK inhibitors.
Inability to swallow capsules, refractory nausea and vomiting, chronic gastrointestinal diseases (eg, inflammatory bowel disease) or significant bowel resection that would preclude adequate absorption.
Taking medication that significantly induces or inhibits CYP3A4.

Study design

Phase: Phase 2
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel assignment
Masking: Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment: 83 participants (actual)

Study arms

Experimental
Docetaxel and AZD6244
Docetaxel with AZD6244
Drug: Docetaxel and AZD6244
Experimental
Docetaxel and Placebo
Docetaxel without AZD6244
Drug: Docetaxel and placebo

Interventions

DrugDocetaxel and AZD6244
Docetaxel 75mg/m2 IV and AZD6244 75mg bd daily. Docetaxel will be administered every 3 weeks for a maximum 6 cycles, but AZD6244 may be continued beyond this, until disease progression.
Also known as: Taxotere
DrugDocetaxel and placebo
Docetaxel 75mg/m2 IV and placebo given bd. Docetaxel will be administered every 3 weeks for a maximum 6 cycles, but placebo may be continued beyond this, until disease progression.
Also known as: Taxotere

What researchers measure

Primary outcomes

Progression Free Survival
This is defined as time from date of randomisation to the first of date of progression (using CT scan, x-ray, MRI scan and clinical examination) using modified RECIST (v1.1) criteria or date of death (events). For patients without an event, the time from date of randomisation to date last known alive will be the censored PFS time.
Time frame: From randomisation date to date of PFS event, if they did not have an event by the end of trial datalock (01Oct2012), an average of 9.3 months.

Secondary outcomes

Progression Free Survival Rate at 6 Months
PFS at 6 months is defined as the percentage progression free survival at 6 months from the PFS Kaplan Meier graph. This would allow all patients randomised to be included. progression was diagnosed using CT scan, x-ray, MRI scan and clinical examination using modified RECIST(v1.1) criteria.
Time frame: From randomisation date to date of PFS event, if they did not have an event by the end of trial datalock (01Oct2012), an average of 9.3 months.
Overall Survival
This is defined as the time from randomisation to death (event) or time from randomisation to date last known alive (censored time).
Time frame: From randomisation date to date of PFS event, if they did not have an event by the end of trial datalock (01Oct2012), an average of 9.3 months.
Objective Response Rate
Objective response rate calculated as number of patients with Complete Response (CR) or Partial response (PR) over all patients randomised. The numerator of the objective response rate is the number of patients achieving a CR or PR. The denominator is all patients randomised. RECIST(v1.1) criteria was used for assessment.
Time frame: From randomisation date to date of PFS event, if they did not have an event by the end of trial datalock (01Oct2012), an average of 9.3 months.
Overall Survival Results - Post Final Analysis
OS analysis was carried out at the final analysis time point on data taken on 01Oct2012. Another data extraction was taken on 05Mar2013 in order to carry out posthoc analyses, OS was analysed again on this data. OS is time from randomisation to death (event) or time from randomisation to date last known alive (censored time).
Time frame: From randomisation date to date of PFS event, if they did not have an event by the end of trial datalock (01Oct2012), an average of 9.3 months.
Vital Signs - Temperature
Vital signs - temperature.
Time frame: From randomisation date to date of PFS event, if they did not have an event by the end of trial datalock (01Oct2012), an average of 9.3 months. Reported value for each arm is median value across all time-points for all patients in that arm.
Vital Signs - Pulse Rate
Vital signs - pulse rate.
Time frame: From randomisation date to date of PFS event, if they did not have an event by the end of trial datalock (01Oct2012), an average of 9.3 months. Reported value for each arm is median value across all time-points for all patients in that arm.
Vital Signs - Systolic Blood Pressure
Vital signs - systolic blood pressure.
Time frame: From randomisation date to date of PFS event, if they did not have an event by the end of trial datalock (01Oct2012), an average of 9.3 months. Reported value for each arm is median value across all time-points for all patients in that arm.
Vital Signs - Diastolic Blood Pressure
Vital signs - diastolic blood pressure.
Time frame: From randomisation date to date of PFS event, if they did not have an event by the end of trial datalock (01Oct2012), an average of 9.3 months. Reported value for each arm is median value across all time-points for all patients in that arm.
Weight
Weight.
Time frame: From randomisation date to date of PFS event, if they did not have an event by the end of trial datalock (01Oct2012), an average of 9.3 months. Reported value for each arm is median value across all time-points for all patients in that arm.
Haematology - Haemoglobin
Haematology - haemoglobin.
Time frame: From randomisation date to date of PFS event, if they did not have an event by the end of trial datalock (01Oct2012), an average of 9.3 months. Reported value for each arm is median value across all time-points for all patients in that arm.
Haematology - White Cell Count
Haematology - white cell count.
Time frame: From randomisation date to date of PFS event, if they did not have an event by the end of trial datalock (01Oct2012), an average of 9.3 months. Reported values for each arm are median values across all time-points for all patients in that arm.
Haematology - Neutrophils
Haematology - neutrophils.
Time frame: From randomisation date to date of PFS event, if they did not have an event by the end of trial datalock (01Oct2012), an average of 9.3 months. Reported value for each arm is median value across all time-points for all patients in that arm.
Haematology - Platelets
Haematology - platelets.
Time frame: From randomisation date to date of PFS event, if they did not have an event by the end of trial datalock (01Oct2012), an average of 9.3 months. Reported value for each arm is median value across all time-points for all patients in that arm.
Biochemistry - Phosphate
Biochemistry - phosphate.
Time frame: From randomisation date to date of PFS event, if they did not have an event by the end of trial datalock (01Oct2012), an average of 9.3 months. Reported value for each arm is median value across all time-points for all patients in that arm.
Biochemistry - Calcium
Biochemistry - calcium.
Time frame: From randomisation date to date of PFS event, if they did not have an event by the end of trial datalock (01Oct2012), an average of 9.3 months. Reported value for each arm is median value across all time-points for all patients in that arm.
Biochemistry - Sodium
Biochemistry - sodium.
Time frame: From randomisation date to date of PFS event, if they did not have an event by the end of trial datalock (01Oct2012), an average of 9.3 months. Reported value for each arm is median value across all time-points for all patients in that arm.
Biochemistry - Potassium
Biochemistry - potassium.
Time frame: From randomisation date to date of PFS event, if they did not have an event by the end of trial datalock (01Oct2012), an average of 9.3 months. Reported value for each arm is median value across all time-points for all patients in that arm.
Biochemistry - Urea
Biochemistry - urea.
Time frame: From randomisation date to date of PFS event, if they did not have an event by the end of trial datalock (01Oct2012), an average of 9.3 months. Reported value for each arm is median value across all time-points for all patients in that arm.
Biochemistry - Bilirubin
Biochemistry - bilirubin.
Time frame: From randomisation date to date of PFS event, if they did not have an event by the end of trial datalock (01Oct2012), an average of 9.3 months. Reported value for each arm is median value across all time-points for all patients in that arm.
Biochemistry - Alkaline Phosphatase
Biochemistry - alkaline phosphatase.
Time frame: From randomisation date to date of PFS event, if they did not have an event by the end of trial datalock (01Oct2012), an average of 9.3 months. Reported value for each arm is median value across all time-points for all patients in that arm.
Biochemistry - ALT
Biochemistry - ALT.
Time frame: From randomisation date to date of PFS event, if they did not have an event by the end of trial datalock (01Oct2012), an average of 9.3 months. Reported value for each arm is median value across all time-points for all patients in that arm.
Biochemistry - AST
Biochemistry - AST.
Time frame: From randomisation date to date of PFS event, if they did not have an event by the end of trial datalock (01Oct2012), an average of 9.3 months. Reported value for each arm is median value across all time-points for all patients in that arm.
Biochemistry - Albumin
Biochemistry - albumin.
Time frame: From randomisation date to date of PFS event, if they did not have an event by the end of trial datalock (01Oct2012), an average of 9.3 months. Reported value for each arm is median value across all time-points for all patients in that arm.
Biochemistry - GGT
Biochemistry - GGT.
Time frame: From randomisation date to date of PFS event, if they did not have an event by the end of trial datalock (01Oct2012), an average of 9.3 months. Reported value for each arm is median value across all time-points for all patients in that arm.
Biochemistry - Total Protein
Biochemistry - total protein.
Time frame: From randomisation date to date of PFS event, if they did not have an event by the end of trial datalock (01Oct2012), an average of 9.3 months. Reported value for each arm is median value across all time-points for all patients in that arm.
Biochemistry - LDH
Biochemistry - LDH.
Time frame: From randomisation date to date of PFS event, if they did not have an event by the end of trial datalock (01Oct2012), an average of 9.3 months. Reported value for each arm is median value across all time-points for all patients in that arm.
Biochemistry - Creatinine
Biochemistry - creatinine.
Time frame: From randomisation date to date of PFS event, if they did not have an event by the end of trial datalock (01Oct2012), an average of 9.3 months. Reported value for each arm is median value across all time-points for all patients in that arm.
Physical Assessment - General Appearance
Physical assessment - general appearance.
Time frame: From randomisation date to date of PFS event, if they did not have an event by the end of trial datalock (01Oct2012), an average of 9.3 months. Reported values for each arm are total counts across all time-points for all patients in that arm.
Physical Exam - Skin
Physical exam - skin.
Time frame: From randomisation date to date of PFS event, if they did not have an event by the end of trial datalock (01Oct2012), an average of 9.3 months. Reported values for each arm are total counts across all time-points for all patients in that arm.
Physical Exam - Head and Neck
Physical exam - head and neck.
Time frame: From randomisation date to date of PFS event, if they did not have an event by the end of trial datalock (01Oct2012), an average of 9.3 months. Reported values for each arm are total counts across all time-points for all patients in that arm.
Physical Exam - Chest
Physical exam - chest.
Time frame: From randomisation date to date of PFS event, if they did not have an event by the end of trial datalock (01Oct2012), an average of 9.3 months. Reported values for each arm are total counts across all time-points for all patients in that arm.
Physical Exam - Cardiovascular
Physical exam - cardiovascular.
Time frame: From randomisation date to date of PFS event, if they did not have an event by the end of trial datalock (01Oct2012), an average of 9.3 months. Reported values for each arm are total counts across all time-points for all patients in that arm.
Physical Exam - Abdomen
Physical exam - abdomen.
Time frame: From randomisation date to date of PFS event, if they did not have an event by the end of trial datalock (01Oct2012), an average of 9.3 months. Reported values for each arm are total counts across all time-points for all patients in that arm.
Physical Exam - Lymph Nodes
Physical exam - lymph nodes.
Time frame: From randomisation date to date of PFS event, if they did not have an event by the end of trial datalock (01Oct2012), an average of 9.3 months. Reported values for each arm are total counts across all time-points for all patients in that arm.
Physical Exam - Extremities
Physical exam - extremities.
Time frame: From randomisation date to date of PFS event, if they did not have an event by the end of trial datalock (01Oct2012), an average of 9.3 months. Reported values for each arm are total counts across all time-points for all patients in that arm.
Physical Exam - Musculoskeletal
Physical exam - musculoskeletal.
Time frame: From randomisation date to date of PFS event, if they did not have an event by the end of trial datalock (01Oct2012), an average of 9.3 months. Reported values for each arm are total counts across all time-points for all patients in that arm.
Physical Exam - Neurological
Physical exam - neurological.
Time frame: From randomisation date to date of PFS event, if they did not have an event by the end of trial datalock (01Oct2012), an average of 9.3 months. Reported values for each arm are total counts across all time-points for all patients in that arm.
Physical Exam - Other
Physical exam - other.
Time frame: From randomisation date to date of PFS event, if they did not have an event by the end of trial datalock (01Oct2012), an average of 9.3 months. Reported values for each arm are total counts across all time-points for all patients in that arm.
ECG - Pre-dose
ECG - pre-dose.
Time frame: From randomisation date to date of PFS event, if they did not have an event by the end of trial datalock (01Oct2012), an average of 9.3 months. Reported values for each arm are total counts across all time-points for all patients in that arm.
ECG - Post-dose
ECG - post-dose.
Time frame: From randomisation date to date of PFS event, if they did not have an event by the end of trial datalock (01Oct2012), an average of 9.3 months. Reported values for each arm are total counts across all time-points for all patients in that arm.
Urinalysis
Urinalysis.
Time frame: From randomisation date to date of PFS event, if they did not have an event by the end of trial datalock (01Oct2012), an average of 9.3 months. Reported values for each arm are total counts across all time-points for all patients in that arm.

Other outcomes

Progression Free Survival: Sensitivity Analysis 1
Same as for primary analysis. This is defined as time from date of randomisation to the first of date of progression (using CT scan, x-ray, MRI scan and clinical examination) using modified RECIST v1.1 criteria or date of death (events). For patients without an event, the time from date of randomisation to date last known alive will be the censored PFS time.
Time frame: From randomisation date to date of PFS event, if they did not have an event by the end of trial datalock (01Oct2012), an average of 9.3 months.
Progression Free Survival- Per Protocol Analysis
Same as for primary analysis. This is defined as time from date of randomisation to the first of date of progression (using CT scan, x-ray, MRI scan and clinical examination) using modified RECIST v1.1. criteria or date of death (events). For patients without an event, the time from date of randomisation to date last known alive will be the censored PFS time.
Time frame: From randomisation date to date of PFS event, if they did not have an event by the end of trial datalock (01Oct2012), an average of 9.3 months.

Results

Posted Aug 15, 2024

Participant flow

Recruitment of 83 participants from 16 centres (hospitals) took place between October 2010 and May 2012. Participants attended clinic visits according to the protocol.

Participant flow — Overall Study
Milestone	Docetaxel and AZD6244	Docetaxel and Placebo
Started	41	42
Completed	38	41
Not completed	3	1
Withdrew: Randomised, later found to be ineligible and did not start treatment	1	1
Withdrew: Randomised and found to be too unwell to start treatment	2	0

Outcome measures

PrimaryProgression Free Survival

This is defined as time from date of randomisation to the first of date of progression (using CT scan, x-ray, MRI scan and clinical examination) using modified RECIST (v1.1) criteria or date of death (events). For patients without an event, the time from date of randomisation to date last known alive will be the censored PFS time.

Time frame:: From randomisation date to date of PFS event, if they did not have an event by the end of trial datalock (01Oct2012), an average of 9.3 months.
Reported as:: Median · months

Progression Free Survival
months	Docetaxel and AZD6244	Docetaxel and Placebo
Progression Free Survival	4.23 (3.63 to 6.90)	3.93 (2.07 to 4.16)

Statistical analysis

Docetaxel and AZD6244 vs Docetaxel and Placebo · Regression, Cox · p = 0.130 (p value \< 0.1 one-sided considered to be significant.) · Hazard ratio (hr): 0.753 · 90% CI 0.498 to 1.138HR is Adjusted for M status, performance status
Docetaxel and AZD6244 vs Docetaxel and Placebo · Regression, Cox · p = 0.113 · Hazard ratio (hr): 0.723 · 90% CI 0.465 to 1.123This includes all 83 patients but the analysis additionally adjusted for LDH, target lesion sum and time interval between randomisation and baseline CT scan as well as mstatus, performance status
Docetaxel and AZD6244 vs Docetaxel and Placebo · Generalised log-rank · p = 0.3016 (This analysis assesses if allowing for interval censoring is consistent with the primary outcome results.)Generalised log-rank taking into account interval censoring, analysed using SAS package version 9.2. Method by Zhao and Sun, 2004
Docetaxel and AZD6244 vs Docetaxel and Placebo · Regression, Cox · p = 0.305 · Hazard ratio (hr): 1.348 · 90% CI 0.602 to 3.016Adjusted for centre

SecondaryProgression Free Survival Rate at 6 Months

PFS at 6 months is defined as the percentage progression free survival at 6 months from the PFS Kaplan Meier graph. This would allow all patients randomised to be included. progression was diagnosed using CT scan, x-ray, MRI scan and clinical examination using modified RECIST(v1.1) criteria.

Time frame:: From randomisation date to date of PFS event, if they did not have an event by the end of trial datalock (01Oct2012), an average of 9.3 months.
Reported as:: Number · percentage of participants

Progression Free Survival Rate at 6 Months
percentage of participants	Docetaxel and AZD6244	Docetaxel and Placebo
Progression Free Survival Rate at 6 Months	40 (27 to 53)	26 (15 to 38)

Statistical analysis

Docetaxel and AZD6244 vs Docetaxel and Placebo · Log Rank · p = 0.187 · Mean difference (final values): 14 · 90% CI -3.4 to 31.4This is the estimated difference in PFS rate i.e. % difference between arms

SecondaryOverall Survival

This is defined as the time from randomisation to death (event) or time from randomisation to date last known alive (censored time).

Time frame:: From randomisation date to date of PFS event, if they did not have an event by the end of trial datalock (01Oct2012), an average of 9.3 months.
Reported as:: Median · months

Overall Survival
months	Docetaxel and AZD6244	Docetaxel and Placebo
Overall Survival	9.5 (8.467 to 12.9)	11.367 (7.467 to 18)

Statistical analysis

Docetaxel and AZD6244 vs Docetaxel and Placebo · Regression, Cox · p = 0.169 · Hazard ratio (hr): 1.373 · 90% CI 0.797 to 2.369p value \< 0.1 one-sided considered to be significant.

SecondaryObjective Response Rate

Objective response rate calculated as number of patients with Complete Response (CR) or Partial response (PR) over all patients randomised. The numerator of the objective response rate is the number of patients achieving a CR or PR. The denominator is all patients randomised. RECIST(v1.1) criteria was used for assessment.

Time frame:: From randomisation date to date of PFS event, if they did not have an event by the end of trial datalock (01Oct2012), an average of 9.3 months.
Reported as:: Count of participants · Participants

Objective Response Rate
Participants	Docetaxel and AZD6244	Docetaxel and Placebo
Complete response	1	0
Partial response	12	6
Stable disease	14	15
Progressive disease	5	19
Not applicable	9	2

Statistical analysis

Docetaxel and AZD6244 vs Docetaxel and Placebo · Chi-squared · p = 0.059

SecondaryOverall Survival Results - Post Final Analysis

OS analysis was carried out at the final analysis time point on data taken on 01Oct2012. Another data extraction was taken on 05Mar2013 in order to carry out posthoc analyses, OS was analysed again on this data. OS is time from randomisation to death (event) or time from randomisation to date last known alive (censored time).

Time frame:: From randomisation date to date of PFS event, if they did not have an event by the end of trial datalock (01Oct2012), an average of 9.3 months.
Reported as:: Median · months

Overall Survival Results - Post Final Analysis
months	Docetaxel and AZD6244	Docetaxel and Placebo
Overall Survival Results - Post Final Analysis	9.5 (8.47 to 12.53)	11.37 (8.67 to 16.03)

Statistical analysis

Docetaxel and AZD6244 vs Docetaxel and Placebo · Regression, Cox · p = 0.318 · Hazard ratio (hr): 1.15 · 90% CI 0.71 to 1.84

SecondaryVital Signs - Temperature

Vital signs - temperature.

Time frame:: From randomisation date to date of PFS event, if they did not have an event by the end of trial datalock (01Oct2012), an average of 9.3 months. Reported value for each arm is median value across all time-points for all patients in that arm.
Reported as:: Median · Degree celsius

Vital Signs - Temperature
Degree celsius	Docetaxel and AZD6244	Docetaxel and Placebo
Vital Signs - Temperature	36.2 (35.9 to 36.6)	36.3 (35.9 to 36.7)

SecondaryVital Signs - Pulse Rate

Vital signs - pulse rate.

Time frame:: From randomisation date to date of PFS event, if they did not have an event by the end of trial datalock (01Oct2012), an average of 9.3 months. Reported value for each arm is median value across all time-points for all patients in that arm.
Reported as:: Median · Beats per minute

Vital Signs - Pulse Rate
Beats per minute	Docetaxel and AZD6244	Docetaxel and Placebo
Vital Signs - Pulse Rate	78 (69 to 88)	84 (72 to 96)

SecondaryVital Signs - Systolic Blood Pressure

Vital signs - systolic blood pressure.

Time frame:: From randomisation date to date of PFS event, if they did not have an event by the end of trial datalock (01Oct2012), an average of 9.3 months. Reported value for each arm is median value across all time-points for all patients in that arm.
Reported as:: Median · Mg mercury

Vital Signs - Systolic Blood Pressure
Mg mercury	Docetaxel and AZD6244	Docetaxel and Placebo
Vital Signs - Systolic Blood Pressure	131 (121 to 144)	130 (120 to 140)

SecondaryVital Signs - Diastolic Blood Pressure

Vital signs - diastolic blood pressure.

Time frame:: From randomisation date to date of PFS event, if they did not have an event by the end of trial datalock (01Oct2012), an average of 9.3 months. Reported value for each arm is median value across all time-points for all patients in that arm.
Reported as:: Median · Mg mercury

Vital Signs - Diastolic Blood Pressure
Mg mercury	Docetaxel and AZD6244	Docetaxel and Placebo
Vital Signs - Diastolic Blood Pressure	82 (73 to 90)	79 (71 to 85)

SecondaryWeight

Weight.

Time frame:: From randomisation date to date of PFS event, if they did not have an event by the end of trial datalock (01Oct2012), an average of 9.3 months. Reported value for each arm is median value across all time-points for all patients in that arm.
Reported as:: Median · Kg

Weight
Kg	Docetaxel and AZD6244	Docetaxel and Placebo
Weight	90.425 (80.95 to 99.1)	83.45 (68.2 to 96.7)

SecondaryHaematology - Haemoglobin

Haematology - haemoglobin.

Time frame:: From randomisation date to date of PFS event, if they did not have an event by the end of trial datalock (01Oct2012), an average of 9.3 months. Reported value for each arm is median value across all time-points for all patients in that arm.
Reported as:: Median · grams per litre

Haematology - Haemoglobin
grams per litre	Docetaxel and AZD6244	Docetaxel and Placebo
Haematology - Haemoglobin	12.5 (11.6 to 13.6)	12.9 (11.7 to 13.9)

SecondaryHaematology - White Cell Count

Haematology - white cell count.

Time frame:: From randomisation date to date of PFS event, if they did not have an event by the end of trial datalock (01Oct2012), an average of 9.3 months. Reported values for each arm are median values across all time-points for all patients in that arm.
Reported as:: Median · 10^9 cells litre

Haematology - White Cell Count
10^9 cells litre	Docetaxel and AZD6244	Docetaxel and Placebo
Haematology - White Cell Count	7.75 (5.1 to 11.2)	8.405 (4.84 to 13.295)

SecondaryHaematology - Neutrophils

Haematology - neutrophils.

Time frame:: From randomisation date to date of PFS event, if they did not have an event by the end of trial datalock (01Oct2012), an average of 9.3 months. Reported value for each arm is median value across all time-points for all patients in that arm.
Reported as:: Median · 10^9 cells litre

Haematology - Neutrophils
10^9 cells litre	Docetaxel and AZD6244	Docetaxel and Placebo
Haematology - Neutrophils	5.4 (2.64 to 8.82)	5.7 (2.85 to 11.46)

SecondaryHaematology - Platelets

Haematology - platelets.

Time frame:: From randomisation date to date of PFS event, if they did not have an event by the end of trial datalock (01Oct2012), an average of 9.3 months. Reported value for each arm is median value across all time-points for all patients in that arm.
Reported as:: Median · 10^9 cells litre

Haematology - Platelets
10^9 cells litre	Docetaxel and AZD6244	Docetaxel and Placebo
Haematology - Platelets	267 (223 to 324)	290.5 (229.5 to 363)

SecondaryBiochemistry - Phosphate

Biochemistry - phosphate.

Time frame:: From randomisation date to date of PFS event, if they did not have an event by the end of trial datalock (01Oct2012), an average of 9.3 months. Reported value for each arm is median value across all time-points for all patients in that arm.
Reported as:: Median · mmol per litre

Biochemistry - Phosphate
mmol per litre	Docetaxel and AZD6244	Docetaxel and Placebo
Biochemistry - Phosphate	1.245 (1.08 to 1.43)	1 (0.86 to 1.16)

SecondaryBiochemistry - Calcium

Biochemistry - calcium.

Time frame:: From randomisation date to date of PFS event, if they did not have an event by the end of trial datalock (01Oct2012), an average of 9.3 months. Reported value for each arm is median value across all time-points for all patients in that arm.
Reported as:: Median · mmol per litre

Biochemistry - Calcium
mmol per litre	Docetaxel and AZD6244	Docetaxel and Placebo
Biochemistry - Calcium	2.28 (2.2 to 2.36)	2.34 (2.26 to 2.43)

SecondaryBiochemistry - Sodium

Biochemistry - sodium.

Time frame:: From randomisation date to date of PFS event, if they did not have an event by the end of trial datalock (01Oct2012), an average of 9.3 months. Reported value for each arm is median value across all time-points for all patients in that arm.
Reported as:: Median · mmol per litre

Biochemistry - Sodium
mmol per litre	Docetaxel and AZD6244	Docetaxel and Placebo
Biochemistry - Sodium	139 (137 to 141)	139 (137 to 140)

SecondaryBiochemistry - Potassium

Biochemistry - potassium.

Time frame:: From randomisation date to date of PFS event, if they did not have an event by the end of trial datalock (01Oct2012), an average of 9.3 months. Reported value for each arm is median value across all time-points for all patients in that arm.
Reported as:: Median · mmol per litre

Biochemistry - Potassium
mmol per litre	Docetaxel and AZD6244	Docetaxel and Placebo
Biochemistry - Potassium	4.3 (4 to 4.54)	4.3 (4 to 4.6)

SecondaryBiochemistry - Urea

Biochemistry - urea.

Time frame:: From randomisation date to date of PFS event, if they did not have an event by the end of trial datalock (01Oct2012), an average of 9.3 months. Reported value for each arm is median value across all time-points for all patients in that arm.
Reported as:: Median · mmol per litre

Biochemistry - Urea
mmol per litre	Docetaxel and AZD6244	Docetaxel and Placebo
Biochemistry - Urea	5.7 (4.7 to 6.6)	5.2 (4.1 to 6.4)

SecondaryBiochemistry - Bilirubin

Biochemistry - bilirubin.

Time frame:: From randomisation date to date of PFS event, if they did not have an event by the end of trial datalock (01Oct2012), an average of 9.3 months. Reported value for each arm is median value across all time-points for all patients in that arm.
Reported as:: Median · umol per litre

Biochemistry - Bilirubin
umol per litre	Docetaxel and AZD6244	Docetaxel and Placebo
Biochemistry - Bilirubin	7 (5 to 10)	7 (5 to 10)

SecondaryBiochemistry - Alkaline Phosphatase

Biochemistry - alkaline phosphatase.

Time frame:: From randomisation date to date of PFS event, if they did not have an event by the end of trial datalock (01Oct2012), an average of 9.3 months. Reported value for each arm is median value across all time-points for all patients in that arm.
Reported as:: Median · IU per litre

Biochemistry - Alkaline Phosphatase
IU per litre	Docetaxel and AZD6244	Docetaxel and Placebo
Biochemistry - Alkaline Phosphatase	93 (72 to 147)	85 (64 to 153)

SecondaryBiochemistry - ALT

Biochemistry - ALT.

Time frame:: From randomisation date to date of PFS event, if they did not have an event by the end of trial datalock (01Oct2012), an average of 9.3 months. Reported value for each arm is median value across all time-points for all patients in that arm.
Reported as:: Median · IU per litre

Biochemistry - ALT
IU per litre	Docetaxel and AZD6244	Docetaxel and Placebo
Biochemistry - ALT	32 (23 to 47)	21 (16 to 31)

SecondaryBiochemistry - AST

Biochemistry - AST.

Time frame:: From randomisation date to date of PFS event, if they did not have an event by the end of trial datalock (01Oct2012), an average of 9.3 months. Reported value for each arm is median value across all time-points for all patients in that arm.
Reported as:: Median · IU per litre

Biochemistry - AST
IU per litre	Docetaxel and AZD6244	Docetaxel and Placebo
Biochemistry - AST	32 (25 to 41)	20 (17 to 26)

SecondaryBiochemistry - Albumin

Biochemistry - albumin.

Time frame:: From randomisation date to date of PFS event, if they did not have an event by the end of trial datalock (01Oct2012), an average of 9.3 months. Reported value for each arm is median value across all time-points for all patients in that arm.
Reported as:: Median · grams per litre

Biochemistry - Albumin
grams per litre	Docetaxel and AZD6244	Docetaxel and Placebo
Biochemistry - Albumin	37 (34 to 41)	40 (37 to 43)

SecondaryBiochemistry - GGT

Biochemistry - GGT.

Time frame:: From randomisation date to date of PFS event, if they did not have an event by the end of trial datalock (01Oct2012), an average of 9.3 months. Reported value for each arm is median value across all time-points for all patients in that arm.
Reported as:: Median · grams per litre

Biochemistry - GGT
grams per litre	Docetaxel and AZD6244	Docetaxel and Placebo
Biochemistry - GGT	41 (26 to 73)	30 (20 to 52)

SecondaryBiochemistry - Total Protein

Biochemistry - total protein.

Time frame:: From randomisation date to date of PFS event, if they did not have an event by the end of trial datalock (01Oct2012), an average of 9.3 months. Reported value for each arm is median value across all time-points for all patients in that arm.
Reported as:: Median · grams per litre

Biochemistry - Total Protein
grams per litre	Docetaxel and AZD6244	Docetaxel and Placebo
Biochemistry - Total Protein	66 (62 to 71)	67 (63 to 71)

SecondaryBiochemistry - LDH

Biochemistry - LDH.

Time frame:: From randomisation date to date of PFS event, if they did not have an event by the end of trial datalock (01Oct2012), an average of 9.3 months. Reported value for each arm is median value across all time-points for all patients in that arm.
Reported as:: Median · Units per litre

Biochemistry - LDH
Units per litre	Docetaxel and AZD6244	Docetaxel and Placebo
Biochemistry - LDH	305 (243 to 491)	386.5 (233 to 499)

SecondaryBiochemistry - Creatinine

Biochemistry - creatinine.

Time frame:: From randomisation date to date of PFS event, if they did not have an event by the end of trial datalock (01Oct2012), an average of 9.3 months. Reported value for each arm is median value across all time-points for all patients in that arm.
Reported as:: Median · milligrams per decalitre

Biochemistry - Creatinine
milligrams per decalitre	Docetaxel and AZD6244	Docetaxel and Placebo
Biochemistry - Creatinine	113.6 (94 to 139.26)	98.3 (83.5 to 119.18)

SecondaryPhysical Assessment - General Appearance

Physical assessment - general appearance.

Time frame:: From randomisation date to date of PFS event, if they did not have an event by the end of trial datalock (01Oct2012), an average of 9.3 months. Reported values for each arm are total counts across all time-points for all patients in that arm.
Reported as:: Count of units · Data points

Physical Assessment - General Appearance
Data points	Docetaxel and AZD6244	Docetaxel and Placebo
Normal	181	162
Abnormal	35	24
Not evaluated	18	12

SecondaryPhysical Exam - Skin

Physical exam - skin.

Time frame:: From randomisation date to date of PFS event, if they did not have an event by the end of trial datalock (01Oct2012), an average of 9.3 months. Reported values for each arm are total counts across all time-points for all patients in that arm.
Reported as:: Count of units · Data points

Physical Exam - Skin
Data points	Docetaxel and AZD6244	Docetaxel and Placebo
Normal	56	86
Abnormal	155	99
Not evaluated	23	12

SecondaryPhysical Exam - Head and Neck

Physical exam - head and neck.

Time frame:: From randomisation date to date of PFS event, if they did not have an event by the end of trial datalock (01Oct2012), an average of 9.3 months. Reported values for each arm are total counts across all time-points for all patients in that arm.
Reported as:: Count of units · Data points

Physical Exam - Head and Neck
Data points	Docetaxel and AZD6244	Docetaxel and Placebo
Normal	139	146
Abnormal	61	23
Not evaluated	34	28

SecondaryPhysical Exam - Chest

Physical exam - chest.

Time frame:: From randomisation date to date of PFS event, if they did not have an event by the end of trial datalock (01Oct2012), an average of 9.3 months. Reported values for each arm are total counts across all time-points for all patients in that arm.
Reported as:: Count of units · Data points

Physical Exam - Chest
Data points	Docetaxel and AZD6244	Docetaxel and Placebo
Normal	187	170
Abnormal	29	16
Not evaluated	18	11

SecondaryPhysical Exam - Cardiovascular

Physical exam - cardiovascular.

Time frame:: From randomisation date to date of PFS event, if they did not have an event by the end of trial datalock (01Oct2012), an average of 9.3 months. Reported values for each arm are total counts across all time-points for all patients in that arm.
Reported as:: Count of units · Data points

Physical Exam - Cardiovascular
Data points	Docetaxel and AZD6244	Docetaxel and Placebo
Normal	204	180
Abnormal	7	6
Not evaluated	23	11

SecondaryPhysical Exam - Abdomen

Physical exam - abdomen.

Time frame:: From randomisation date to date of PFS event, if they did not have an event by the end of trial datalock (01Oct2012), an average of 9.3 months. Reported values for each arm are total counts across all time-points for all patients in that arm.
Reported as:: Count of units · Data points

Physical Exam - Abdomen
Data points	Docetaxel and AZD6244	Docetaxel and Placebo
Normal	205	163
Abnormal	5	24
Not evaluated	24	10

SecondaryPhysical Exam - Lymph Nodes

Physical exam - lymph nodes.

Time frame:: From randomisation date to date of PFS event, if they did not have an event by the end of trial datalock (01Oct2012), an average of 9.3 months. Reported values for each arm are total counts across all time-points for all patients in that arm.
Reported as:: Count of units · Data points

Physical Exam - Lymph Nodes
Data points	Docetaxel and AZD6244	Docetaxel and Placebo
Normal	162	148
Abnormal	19	27
Not evaluated	53	22

SecondaryPhysical Exam - Extremities

Physical exam - extremities.

Time frame:: From randomisation date to date of PFS event, if they did not have an event by the end of trial datalock (01Oct2012), an average of 9.3 months. Reported values for each arm are total counts across all time-points for all patients in that arm.
Reported as:: Count of units · Data points

Physical Exam - Extremities
Data points	Docetaxel and AZD6244	Docetaxel and Placebo
Normal	114	139
Abnormal	83	37
Not evaluated	37	21

SecondaryPhysical Exam - Musculoskeletal

Physical exam - musculoskeletal.

Time frame:: From randomisation date to date of PFS event, if they did not have an event by the end of trial datalock (01Oct2012), an average of 9.3 months. Reported values for each arm are total counts across all time-points for all patients in that arm.
Reported as:: Count of units · Data points

Physical Exam - Musculoskeletal
Data points	Docetaxel and AZD6244	Docetaxel and Placebo
Normal	156	149
Abnormal	19	13
Not evaluated	59	35

SecondaryPhysical Exam - Neurological

Physical exam - neurological.

Time frame:: From randomisation date to date of PFS event, if they did not have an event by the end of trial datalock (01Oct2012), an average of 9.3 months. Reported values for each arm are total counts across all time-points for all patients in that arm.
Reported as:: Count of units · Data points

Physical Exam - Neurological
Data points	Docetaxel and AZD6244	Docetaxel and Placebo
Normal	149	129
Abnormal	7	19
Not evaluated	78	49

SecondaryPhysical Exam - Other

Physical exam - other.

Time frame:: From randomisation date to date of PFS event, if they did not have an event by the end of trial datalock (01Oct2012), an average of 9.3 months. Reported values for each arm are total counts across all time-points for all patients in that arm.
Reported as:: Count of units · Data points

Physical Exam - Other
Data points	Docetaxel and AZD6244	Docetaxel and Placebo
Normal	4	4
Abnormal	40	31
Not evaluated	8	12

SecondaryECG - Pre-dose

ECG - pre-dose.

Time frame:: From randomisation date to date of PFS event, if they did not have an event by the end of trial datalock (01Oct2012), an average of 9.3 months. Reported values for each arm are total counts across all time-points for all patients in that arm.
Reported as:: Count of units · Data points

ECG - Pre-dose
Data points	Docetaxel and AZD6244	Docetaxel and Placebo
Normal	39	39
Abnormal	5	6
Not evalauated	23	77

SecondaryECG - Post-dose

ECG - post-dose.

Time frame:: From randomisation date to date of PFS event, if they did not have an event by the end of trial datalock (01Oct2012), an average of 9.3 months. Reported values for each arm are total counts across all time-points for all patients in that arm.
Reported as:: Count of units · Data points

ECG - Post-dose
Data points	Docetaxel and AZD6244	Docetaxel and Placebo
Normal	32	34
Abnormal	5	6
Not evaluated	31	87

SecondaryUrinalysis

Urinalysis.

Time frame:: From randomisation date to date of PFS event, if they did not have an event by the end of trial datalock (01Oct2012), an average of 9.3 months. Reported values for each arm are total counts across all time-points for all patients in that arm.
Reported as:: Count of units · Data points

Urinalysis
Data points	Docetaxel and AZD6244	Docetaxel and Placebo
Normal	205	229
Abnormal	130	117
Not evaluated	37	19

Other pre-specifiedProgression Free Survival: Sensitivity Analysis 1

Same as for primary analysis. This is defined as time from date of randomisation to the first of date of progression (using CT scan, x-ray, MRI scan and clinical examination) using modified RECIST v1.1 criteria or date of death (events). For patients without an event, the time from date of randomisation to date last known alive will be the censored PFS time.

Time frame:: From randomisation date to date of PFS event, if they did not have an event by the end of trial datalock (01Oct2012), an average of 9.3 months.
Reported as:: Median · months

Progression Free Survival: Sensitivity Analysis 1
months	Docetaxel and AZD6244	Docetaxel and Placebo
Progression Free Survival: Sensitivity Analysis 1	4.1 (2.1 to 4.233)	3.333 (2.067 to 4.167)

Statistical analysis

Docetaxel and AZD6244 vs Docetaxel and Placebo · Regression, Cox · p = 0.468 · Hazard ratio (hr): 1.022 · 90% CI 0.649 to 1.612Analysis Adjusted for M status, performance status

Other pre-specifiedProgression Free Survival- Per Protocol Analysis

Same as for primary analysis. This is defined as time from date of randomisation to the first of date of progression (using CT scan, x-ray, MRI scan and clinical examination) using modified RECIST v1.1. criteria or date of death (events). For patients without an event, the time from date of randomisation to date last known alive will be the censored PFS time.

Time frame:: From randomisation date to date of PFS event, if they did not have an event by the end of trial datalock (01Oct2012), an average of 9.3 months.
Reported as:: Median · months

Progression Free Survival- Per Protocol Analysis
months	Docetaxel and AZD6244	Docetaxel and Placebo
Progression Free Survival- Per Protocol Analysis	4.3 (4.1 to 7.033)	4.067 (2.1 to 4.2)

Statistical analysis

Docetaxel and AZD6244 vs Docetaxel and Placebo · Regression, Cox · p = 0.106 · Hazard ratio (hr): 0.721 · 90% CI 0.468 to 1.109Analysis was adjusted for mstatus, performance status

Post-hocProgression Free Survival: in Patients With NRAS Data

Outcome is time from randomisation to progression or death in subset of patients with NRAS mutational data available and in the per-protocol population. progression was diagnosed using CT scan, x-ray, MRI scan and clinical examination using modified RECIST(v1.1) criteria. NRAS mutational analysis (wild type or mutated) for all patients was derived from archival melanoma tumour tissue samples.

Time frame:: From randomisation date to date of PFS event, if they did not have an event by the end of trial datalock (01Oct2012), an average of 9.3 months.
Reported as:: Median · months

Progression Free Survival: in Patients With NRAS Data
months	Docetaxel and AZD6244	Docetaxel and Placebo
Progression Free Survival: in Patients With NRAS Data	4.4 (3.4 to 7.13)	4.1 (2.07 to 4.2)

Statistical analysis

Docetaxel and AZD6244 vs Docetaxel and Placebo · Regression, Cox · p = 0.824 (p-value is for the interaction term) · Hazard ratio (hr): 0.63 · 95% CI 0.25 to 1.53HRs (95% CI) between treatment groups are given for Wild type and NRAS mutated separately. The above HR is for WT.

Post-hocOverall Survival in Patients With NRAS Data

Outcome is time from randomisation to death in subset of patients with NRAS mutational data available and in the per-protocol population. NRAS mutational analysis (wild type or mutated) for all patients was derived from archival melanoma tumour tissue samples.

Time frame:: From randomisation date to date of PFS event, if they did not have an event by the end of trial datalock (01Oct2012), an average of 9.3 months.
Reported as:: Median · months

Overall Survival in Patients With NRAS Data
months	Docetaxel and AZD6244	Docetaxel and Placebo
Overall Survival in Patients With NRAS Data	12.07 (8.47 to 12.9)	11.9 (9.3 to 18)

Statistical analysis

Docetaxel and AZD6244 vs Docetaxel and Placebo · Regression, Cox · p = 0.072 (p-value is for interaction term.) · Hazard ratio (hr): 0.51 · 95% CI 0.16 to 1.60HRs for treatment effect (AZD6244 vs Placebo ) are estimated for NRAS WT and NRAS mutated patients separately. Hazard ratios (95%CI) given above are for NRAS WT patients.
Docetaxel and AZD6244 vs Docetaxel and Placebo · Hazard ratio (hr): 1.97 · 95% CI 0.73 to 5.33HR for NRAS mutated patients

Post-hocObjective Response Rate in Patients With WT NRAS

Best overall response as reported for evaluable/measurable scans including target, non-target and new lesions. Response assessed using RECIST(v1.1) criteria. Data from Mar2013 which was post final data lock

Time frame:: From randomisation date to date of PFS event, if they did not have an event by the end of trial datalock (01Oct2012), an average of 9.3 months.
Reported as:: Count of participants · Participants

Objective Response Rate in Patients With WT NRAS
Participants	Docetaxel and AZD6244	Docetaxel and Placebo
Complete response	0	0
Partial response	2	2
Stable disease	4	4
Progressive disease	3	8
Not applicable	0	0

Post-hocOverall Survival Results - Post Final Analysis- Per-protocol

Time frame:: From randomisation date to date of PFS event, if they did not have an event by the end of trial datalock (01Oct2012), an average of 9.3 months.
Reported as:: Median · months

Overall Survival Results - Post Final Analysis- Per-protocol
months	Docetaxel and AZD6244	Docetaxel and Placebo
Overall Survival Results - Post Final Analysis- Per-protocol	10.9 (8.53 to 12.53)	11.77 (8.67 to 16.03)

Statistical analysis

Docetaxel and AZD6244 vs Docetaxel and Placebo · Regression, Cox · p = 0.348 · Hazard ratio (hr): 1.12 · 90% CI 0.68 to 1.87

Post-hocProgression Free Survival: in Patients With NRAS Data- Sensitivity

Outcome is time from randomisation to progression or death in subset of patients with NRAS mutational data available and in the per-protocol population and excluding patients found to have BRAF mutation on retesting (the inclusion criteria for the trial is those with wildtype BRAF). progression was diagnosed using CT scan, x-ray, MRI scan and clinical examination using modified RECIST(v1.1) criteria. NRAS mutational analysis (wild type or mutated) for all patients was derived from archival melanoma tumour tissue samples.

Time frame:: From randomisation date to date of PFS event, if they did not have an event by the end of trial datalock (01Oct2012), an average of 9.3 months.
Reported as:: Median · months

Progression Free Survival: in Patients With NRAS Data- Sensitivity
months	Docetaxel and AZD6244	Docetaxel and Placebo
Progression Free Survival: in Patients With NRAS Data- Sensitivity	4.4 (3.4 to 7.27)	4.1 (2.07 to 4.27)

Statistical analysis

Docetaxel and AZD6244 vs Docetaxel and Placebo · Regression, Cox · p = 0.797 (p-value is for interaction term.) · Hazard ratio (hr): 0.61 · 90% CI 0.24 to 1.58HRs for treatment effect (AZD6244 vs Placebo ) are estimated for NRAS WT and NRAS mutated patients separately. Hazard ratios (95%CI) given above are for NRAS WT patients.
Docetaxel and AZD6244 vs Docetaxel and Placebo · Hazard ratio (hr): 0.71 · 95% CI 0.350 to 1.45HR for NRAS mutated patients

Post-hocOverall Survival in Patients With NRAS Data- Sensitivity

Outcome is time from randomisation to death in subset of patients with NRAS mutational data available and in the per-protocol population and excluding patients found to have BRAF mutation on retesting (the inclusion criteria for the trial is those with wildtype BRAF). NRAS mutational analysis (wild type or mutated) for all patients was derived from archival melanoma tumour tissue samples.

Time frame:: From randomisation date to date of PFS event, if they did not have an event by the end of trial datalock (01Oct2012), an average of 9.3 months.
Reported as:: Median · months

Overall Survival in Patients With NRAS Data- Sensitivity
months	Docetaxel and AZD6244	Docetaxel and Placebo
Overall Survival in Patients With NRAS Data- Sensitivity	12.07 (8.47 to 12.9)	11.9 (10.43 to 18)

Statistical analysis

Docetaxel and AZD6244 vs Docetaxel and Placebo · Regression, Cox · p = 0.120 (Model includes interaction term between NRAS status and treatment group and stratification variables. p-value is for interaction term.) · Hazard ratio (hr): 0.60 · 95% CI 0.18 to 1.97HRs for treatment effect (AZD6244 vs Placebo ) are estimated for NRAS WT and NRAS mutated patients separately. Hazard ratios (95%CI) given above are for NRAS WT patients.
Docetaxel and AZD6244 vs Docetaxel and Placebo · Hazard ratio (hr): 1.99 · 95% CI 0.73 to 5.38HR for NRAS mutated patients

Post-hocObjective Response Rate in Patients With Mutated NRAS

Time frame:: From randomisation date to date of PFS event, if they did not have an event by the end of trial datalock (01Oct2012), an average of 9.3 months.
Reported as:: Count of participants · Participants

Objective Response Rate in Patients With Mutated NRAS
Participants	Docetaxel and AZD6244	Docetaxel and Placebo
Complete response	1	0
Partial response	6	2
Stable disease	7	9
Progressive disease	2	6
Not applicable	4	0

Adverse events

Collected over 170 days. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
Docetaxel and AZD6244	26/41 (63.4%)	29/41 (70.7%)	35/41 (85.4%)
Docetaxel and Placebo	28/42 (66.7%)	20/42 (47.6%)	40/42 (95.2%)

Most frequent serious events

Showing 10 of 21

Most frequent serious events
Event	Docetaxel and AZD6244	Docetaxel and Placebo
Retinal Vascular DisorderEye disorders	1/1	—
Gastric HaemorrhageGastrointestinal disorders	2/2	0/42
VomitingGastrointestinal disorders	1/41	1/1
DiarrhoeaGastrointestinal disorders	2/2	1/42
DyspneaRespiratory, thoracic and mediastinal disorders	1/1	1/42
Febrile NeutropeniaBlood and lymphatic system disorders	20/41	13/42
FeverGeneral disorders	5/41	2/42
Skin InfectionInfections and infestations	2/41	0/42
SepsisInfections and infestations	2/41	0/42
Lung InfectionInfections and infestations	1/41	2/42

Most frequent other events

Showing 10 of 109

Most frequent other events
Event	Docetaxel and AZD6244	Docetaxel and Placebo
DiarrhoeaGastrointestinal disorders	32/41	20/42
FatigueGeneral disorders	28/41	32/42
Rash AcneiformSkin and subcutaneous tissue disorders	29/41	20/42
Mucositis OralGastrointestinal disorders	20/41	17/42
AlopeciaSkin and subcutaneous tissue disorders	19/41	20/42
NauseaGastrointestinal disorders	19/41	15/42
Pain - OtherMusculoskeletal and connective tissue disorders	17/41	11/42
Localized EdemaGeneral disorders	15/41	8/42
DysgeusiaNervous system disorders	14/41	13/42
Neutrophil Count DecreasedInvestigations	4/41	13/42

Baseline characteristics

All randomised patients

Age, Continuous
Age, Continuous(years)	Docetaxel and AZD6244	Docetaxel and Placebo	Total
Mean	59.5 ± 12.0	59.2 ± 13.3	59.3 ± 12.6

Sex: Female, Male
Sex: Female, Male(Participants)	Docetaxel and AZD6244	Docetaxel and Placebo	Total
Female	10	15	25
Male	31	27	58

Region of Enrollment
Region of Enrollment(Participants)	Docetaxel and AZD6244	Docetaxel and Placebo	Total
United Kingdom	41	42	83

Stage
Stage(Participants)	Docetaxel and AZD6244	Docetaxel and Placebo	Total
M1c	33	32	65
M0 or M1a or M1b	8	10	18

ECOG Performance Score
ECOG Performance Score(Participants)	Docetaxel and AZD6244	Docetaxel and Placebo	Total
0	28	34	62
1	13	8	21

Smoking status
Smoking status(Participants)	Docetaxel and AZD6244	Docetaxel and Placebo	Total
Yes	4	3	7
No, but smoked in the past	22	27	49
Never smoked	15	12	27

Physical examination
Physical examination(Participants)	Docetaxel and AZD6244	Docetaxel and Placebo	Total
General appearance	0	1	1
Skin	21	13	34
HEENT	1	4	5
Chest	4	5	9
Cardiovascular	0	0	0
Abdomen	5	2	7
Lymph nodes	7	8	15
Extremities/back	7	7	14
Musculoskeletal	2	4	6
Neurological	1	2	3
Other body system	2	4	6

Vital Signs: temperature
Vital Signs: temperature(degrees C)	Docetaxel and AZD6244	Docetaxel and Placebo	Total
Median	36.2 (35.2 to 37.3)	36.5 (35 to 37.4)	36.4 (35 to 37.4)

16 further baseline measures are reported on the registry.

Study locations

1 site

Churchill Hospital
Oxford, Oxfordshire OX3 7LJ, United Kingdom

References and documents

Study documents

Study protocol · Jul 29, 2014
Statistical analysis plan · Feb 28, 2013

Documents are hosted by the registry — open the source record to download them.

Updates

Tracking since Sep 25, 2026

No changes since tracking began. The registry record was last updated on Aug 15, 2024, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT01256359
Lead sponsor: University of Oxford
Responsible party: Sponsor
First posted: Dec 8, 2010
Start date: Oct 2010
Primary completion: Oct 2012
Completion: Feb 2020
Results posted: Aug 15, 2024
Last update: Aug 15, 2024

Study contacts

Mark R Middleton

principal investigator · University of Oxford

Oversight

Data monitoring committee: No

View the source record on ClinicalTrials.gov ↗

Not currently enrolling

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Docetaxel With or Without AZD6244 in Melanoma

Study summary

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Melanoma

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