Trial Outcomes & Findings for Comparison of AZD6244 in Combination With Dacarbazine Versus (vs) Dacarbazine Alone in BRAF Mutation Positive Melanoma Patients (NCT NCT00936221)
NCT ID: NCT00936221
Last Updated: 2016-03-14
Results Overview
Following progression survival data was collected until documentation of death, withdrawal of consent, loss to follow-up or the final data cut-off, whichever occurred first.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
385 participants
Primary outcome timeframe
From date of randomization until death, withdrawal of consent or the end of the study. The end of the study was defined as the date all AZD6244 patients had been followed for a minimum of 12 months, or the date of final analysis, whichever was later
Results posted on
2016-03-14
Participant Flow
Participant milestones
| Measure |
Selumetinib 75mg BD +Dacarbazine
selumetinib 75mg twice daily + Dacarbazine
|
Placebo BD + Dacarbazine
Placebo twice daily + Dacarbazine
|
|---|---|---|
|
Overall Study
STARTED
|
45
|
46
|
|
Overall Study
Received Treatment
|
44
|
45
|
|
Overall Study
COMPLETED
|
44
|
45
|
|
Overall Study
NOT COMPLETED
|
1
|
1
|
Reasons for withdrawal
| Measure |
Selumetinib 75mg BD +Dacarbazine
selumetinib 75mg twice daily + Dacarbazine
|
Placebo BD + Dacarbazine
Placebo twice daily + Dacarbazine
|
|---|---|---|
|
Overall Study
Withdrawal by Subject
|
1
|
1
|
Baseline Characteristics
Comparison of AZD6244 in Combination With Dacarbazine Versus (vs) Dacarbazine Alone in BRAF Mutation Positive Melanoma Patients
Baseline characteristics by cohort
| Measure |
Selumetinib 75mg BD +Dacarbazine
n=45 Participants
selumetinib 75mg twice daily + Dacarbazine
|
Placebo BD + Dacarbazine
n=46 Participants
Placebo twice daily + Dacarbazine
|
Total
n=91 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
55.7 Years
STANDARD_DEVIATION 14.89 • n=5 Participants
|
51.6 Years
STANDARD_DEVIATION 16.21 • n=7 Participants
|
53.6 Years
STANDARD_DEVIATION 15.62 • n=5 Participants
|
|
Sex: Female, Male
Female
|
23 Participants
n=5 Participants
|
18 Participants
n=7 Participants
|
41 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
22 Participants
n=5 Participants
|
28 Participants
n=7 Participants
|
50 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: From date of randomization until death, withdrawal of consent or the end of the study. The end of the study was defined as the date all AZD6244 patients had been followed for a minimum of 12 months, or the date of final analysis, whichever was laterPopulation: Intention to Treat (ITT)
Following progression survival data was collected until documentation of death, withdrawal of consent, loss to follow-up or the final data cut-off, whichever occurred first.
Outcome measures
| Measure |
Selumetinib 75mg BD + Dacarbazine
n=45 Participants
selumetinib 75mg twice daily + dacarbazine
|
Placebo + Dacarbazine
n=46 Participants
Matched Placebo + dacarbazine
|
|---|---|---|
|
Overall Survival
|
424 Days
Interval 63.0 to 760.0
|
321 Days
Interval 66.0 to 739.0
|
SECONDARY outcome
Timeframe: From randomization until evidence of RECIST-defined objective disease progression or data cut off, for a minimum of 12 months since start of treatmentPopulation: Intention to Treat (ITT)
PFS is the time from randomisation until the date of objective disease progression as defined by Response Evaluation Criteria In Solid Tumours (RECIST version 1.1) or death (by any cause in the absence of progression). Progression is defined using RECIST (v1.1), as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5mm.
Outcome measures
| Measure |
Selumetinib 75mg BD + Dacarbazine
n=45 Participants
selumetinib 75mg twice daily + dacarbazine
|
Placebo + Dacarbazine
n=46 Participants
Matched Placebo + dacarbazine
|
|---|---|---|
|
Progression Free Survival
|
169 Days
Interval 37.0 to 596.0
|
92 Days
Interval 32.0 to 660.0
|
SECONDARY outcome
Timeframe: From randomization until evidence of RECIST-defined objective disease progression or data cut off, for a minimum of 12 months since start of treatmentPopulation: Intention to Treat (ITT)
ORR rate is defined as the number (%) of subjects with at least one visit response of Complete Response (CR) or Partial Response (PR) , as defined by Response Evaluation Criteria in Solid Tumours (RECIST v1.1) for target lesions and assessed by CT or MRI. CR, Disappearance of all target lesions; PR, ≥30% decrease in the sum of the longest diameter of target lesions. Data obtained up until progression, or last evaluable assessment in the absence of progression, was included in the assessment of ORR
Outcome measures
| Measure |
Selumetinib 75mg BD + Dacarbazine
n=45 Participants
selumetinib 75mg twice daily + dacarbazine
|
Placebo + Dacarbazine
n=46 Participants
Matched Placebo + dacarbazine
|
|---|---|---|
|
Objective Response Rate
Response
|
18 Participants
|
12 Participants
|
|
Objective Response Rate
Complete Response
|
1 Participants
|
1 Participants
|
|
Objective Response Rate
Partial Response
|
17 Participants
|
11 Participants
|
|
Objective Response Rate
Non-response
|
27 Participants
|
34 Participants
|
|
Objective Response Rate
Stable Disease >=6 weeks
|
13 Participants
|
10 Participants
|
|
Objective Response Rate
Progression
|
14 Participants
|
24 Participants
|
SECONDARY outcome
Timeframe: randomization to week 12Population: Intention to Treat (ITT)
Outcome measures
| Measure |
Selumetinib 75mg BD + Dacarbazine
n=45 Participants
selumetinib 75mg twice daily + dacarbazine
|
Placebo + Dacarbazine
n=46 Participants
Matched Placebo + dacarbazine
|
|---|---|---|
|
Change in Target Lesion Tumour Size at Week 12
|
-8.85 % change
Interval -65.22 to 121.77
|
0.22 % change
Interval -72.5 to 295.79
|
Adverse Events
Selumetinib 75mg BD +Dacarbazine
Serious events: 22 serious events
Other events: 44 other events
Deaths: 0 deaths
Placebo BD + Dacarbazine
Serious events: 8 serious events
Other events: 44 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Selumetinib 75mg BD +Dacarbazine
n=44 participants at risk
selumetinib 75mg twice daily + Dacarbazine
|
Placebo BD + Dacarbazine
n=45 participants at risk
Placebo twice daily + Dacarbazine
|
|---|---|---|
|
Infections and infestations
Erysipelas
|
4.5%
2/44
|
0.00%
0/45
|
|
Infections and infestations
Cellulitis
|
2.3%
1/44
|
0.00%
0/45
|
|
Infections and infestations
Clostridium difficile colitis
|
2.3%
1/44
|
0.00%
0/45
|
|
Infections and infestations
Device related infection
|
2.3%
1/44
|
0.00%
0/45
|
|
Infections and infestations
Infection
|
2.3%
1/44
|
0.00%
0/45
|
|
Infections and infestations
Lower respiratory tract infection
|
2.3%
1/44
|
0.00%
0/45
|
|
Infections and infestations
Sepsis
|
2.3%
1/44
|
4.4%
2/45
|
|
Infections and infestations
Neutropenic sepsis
|
0.00%
0/44
|
2.2%
1/45
|
|
Infections and infestations
Pneumonia
|
0.00%
0/44
|
2.2%
1/45
|
|
Gastrointestinal disorders
Abdominal pain
|
6.8%
3/44
|
2.2%
1/45
|
|
Gastrointestinal disorders
Vomiting
|
4.5%
2/44
|
2.2%
1/45
|
|
Gastrointestinal disorders
Diarrhoea
|
2.3%
1/44
|
0.00%
0/45
|
|
Gastrointestinal disorders
Constipation
|
0.00%
0/44
|
2.2%
1/45
|
|
Blood and lymphatic system disorders
Disseminated intravascular coagulation
|
2.3%
1/44
|
0.00%
0/45
|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
2.3%
1/44
|
0.00%
0/45
|
|
Blood and lymphatic system disorders
Neutropenia
|
2.3%
1/44
|
0.00%
0/45
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
2.3%
1/44
|
2.2%
1/45
|
|
Blood and lymphatic system disorders
Anaemia
|
0.00%
0/44
|
2.2%
1/45
|
|
General disorders
Chest pain
|
2.3%
1/44
|
0.00%
0/45
|
|
General disorders
Pyrexia
|
2.3%
1/44
|
0.00%
0/45
|
|
General disorders
Asthenia
|
0.00%
0/44
|
2.2%
1/45
|
|
General disorders
Fatigue
|
0.00%
0/44
|
4.4%
2/45
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Intracranial tumour haemorrhage
|
2.3%
1/44
|
0.00%
0/45
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Prostate cancer
|
2.3%
1/44
|
0.00%
0/45
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Colon cancer
|
0.00%
0/44
|
2.2%
1/45
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea exertional
|
2.3%
1/44
|
0.00%
0/45
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
|
2.3%
1/44
|
2.2%
1/45
|
|
Vascular disorders
Arterial thrombosis limb
|
2.3%
1/44
|
0.00%
0/45
|
|
Vascular disorders
Venous thrombosis limb
|
2.3%
1/44
|
0.00%
0/45
|
|
Vascular disorders
Deep vein thrombosis
|
0.00%
0/44
|
2.2%
1/45
|
|
Cardiac disorders
Left atrial dilatation
|
2.3%
1/44
|
0.00%
0/45
|
|
Eye disorders
Periorbital oedema
|
2.3%
1/44
|
0.00%
0/45
|
|
Eye disorders
Ocular hypertension
|
0.00%
0/44
|
2.2%
1/45
|
|
Eye disorders
Retinal tear
|
0.00%
0/44
|
2.2%
1/45
|
|
Investigations
Alanine aminotransferase increased
|
2.3%
1/44
|
0.00%
0/45
|
|
Investigations
Aspartate aminotransferase increased
|
2.3%
1/44
|
0.00%
0/45
|
|
Musculoskeletal and connective tissue disorders
Groin Pain
|
2.3%
1/44
|
0.00%
0/45
|
|
Nervous system disorders
Syncope
|
2.3%
1/44
|
0.00%
0/45
|
|
Renal and urinary disorders
Renal colic
|
2.3%
1/44
|
0.00%
0/45
|
|
Reproductive system and breast disorders
Prostatitis
|
2.3%
1/44
|
0.00%
0/45
|
|
Skin and subcutaneous tissue disorders
Rash
|
2.3%
1/44
|
0.00%
0/45
|
|
Psychiatric disorders
Completed suicide
|
0.00%
0/44
|
2.2%
1/45
|
Other adverse events
| Measure |
Selumetinib 75mg BD +Dacarbazine
n=44 participants at risk
selumetinib 75mg twice daily + Dacarbazine
|
Placebo BD + Dacarbazine
n=45 participants at risk
Placebo twice daily + Dacarbazine
|
|---|---|---|
|
Blood and lymphatic system disorders
ANAEMIA
|
9.1%
4/44
|
4.4%
2/45
|
|
Blood and lymphatic system disorders
LEUKOPENIA
|
2.3%
1/44
|
6.7%
3/45
|
|
Blood and lymphatic system disorders
NEUTROPENIA
|
15.9%
7/44
|
15.6%
7/45
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
25.0%
11/44
|
13.3%
6/45
|
|
Eye disorders
EYELID OEDEMA
|
6.8%
3/44
|
0.00%
0/45
|
|
Eye disorders
PERIORBITAL OEDEMA
|
9.1%
4/44
|
2.2%
1/45
|
|
Gastrointestinal disorders
Abdominal Pain
|
20.5%
9/44
|
8.9%
4/45
|
|
Gastrointestinal disorders
Abdominal Pain Upper
|
9.1%
4/44
|
8.9%
4/45
|
|
Gastrointestinal disorders
Constipation
|
27.3%
12/44
|
28.9%
13/45
|
|
Gastrointestinal disorders
DIARRHOEA
|
47.7%
21/44
|
28.9%
13/45
|
|
Gastrointestinal disorders
DRY MOUTH
|
13.6%
6/44
|
0.00%
0/45
|
|
Gastrointestinal disorders
DYSPEPSIA
|
13.6%
6/44
|
4.4%
2/45
|
|
Gastrointestinal disorders
FLATULENCE
|
2.3%
1/44
|
11.1%
5/45
|
|
Gastrointestinal disorders
GASTROOESOPHAGEAL REFLUX DISEASE
|
6.8%
3/44
|
0.00%
0/45
|
|
Gastrointestinal disorders
NAUSEA
|
63.6%
28/44
|
55.6%
25/45
|
|
Gastrointestinal disorders
STOMATITIS
|
18.2%
8/44
|
11.1%
5/45
|
|
Gastrointestinal disorders
VOMITING
|
45.5%
20/44
|
31.1%
14/45
|
|
General disorders
ASTHENIA
|
27.3%
12/44
|
11.1%
5/45
|
|
General disorders
CHILLS
|
6.8%
3/44
|
2.2%
1/45
|
|
General disorders
FACE OEDEMA
|
6.8%
3/44
|
2.2%
1/45
|
|
General disorders
FATIGUE
|
36.4%
16/44
|
33.3%
15/45
|
|
General disorders
GENERALISED OEDEMA
|
13.6%
6/44
|
4.4%
2/45
|
|
General disorders
LOCALISED OEDEMA
|
6.8%
3/44
|
0.00%
0/45
|
|
General disorders
OEDEMA PERIPHERAL
|
43.2%
19/44
|
6.7%
3/45
|
|
General disorders
PYREXIA
|
11.4%
5/44
|
11.1%
5/45
|
|
Infections and infestations
FOLLICULITIS
|
11.4%
5/44
|
0.00%
0/45
|
|
Infections and infestations
NASOPHARYNGITIS
|
6.8%
3/44
|
13.3%
6/45
|
|
Infections and infestations
PARONYCHIA
|
13.6%
6/44
|
0.00%
0/45
|
|
Infections and infestations
RASH PUSTULAR
|
13.6%
6/44
|
0.00%
0/45
|
|
Infections and infestations
UPPER RESPIRATORY TRACT INFECTION
|
9.1%
4/44
|
4.4%
2/45
|
|
Infections and infestations
URINARY TRACT INFECTION
|
11.4%
5/44
|
0.00%
0/45
|
|
Investigations
ALANINE AMINOTRANSFERASE INCREASED
|
9.1%
4/44
|
6.7%
3/45
|
|
Investigations
ASPARTATE AMINOTRANSFERASE INCREASED
|
11.4%
5/44
|
2.2%
1/45
|
|
Investigations
BLOOD CREATININE PHOSPHOKINASE INCREASED
|
15.9%
7/44
|
0.00%
0/45
|
|
Investigations
BLOOD PRESSURE INCREASED
|
9.1%
4/44
|
0.00%
0/45
|
|
Investigations
WEIGHT INCREASED
|
6.8%
3/44
|
0.00%
0/45
|
|
Metabolism and nutrition disorders
DECREASED APPETITE
|
22.7%
10/44
|
24.4%
11/45
|
|
Metabolism and nutrition disorders
HYPOKALAEMIA
|
6.8%
3/44
|
0.00%
0/45
|
|
Musculoskeletal and connective tissue disorders
ARTHRALGIA
|
9.1%
4/44
|
6.7%
3/45
|
|
Musculoskeletal and connective tissue disorders
BACK PAIN
|
15.9%
7/44
|
6.7%
3/45
|
|
Musculoskeletal and connective tissue disorders
MYALGIA
|
6.8%
3/44
|
2.2%
1/45
|
|
Musculoskeletal and connective tissue disorders
PAIN IN EXTREMITY
|
6.8%
3/44
|
8.9%
4/45
|
|
Nervous system disorders
DIZZINESS
|
13.6%
6/44
|
4.4%
2/45
|
|
Nervous system disorders
DYSGEUSIA
|
9.1%
4/44
|
8.9%
4/45
|
|
Nervous system disorders
HEADACHE
|
11.4%
5/44
|
26.7%
12/45
|
|
Nervous system disorders
LETHARGY
|
4.5%
2/44
|
8.9%
4/45
|
|
Nervous system disorders
PARAESTHESIA
|
6.8%
3/44
|
8.9%
4/45
|
|
Nervous system disorders
SYNCOPE
|
9.1%
4/44
|
0.00%
0/45
|
|
Psychiatric disorders
ANXIETY
|
11.4%
5/44
|
11.1%
5/45
|
|
Psychiatric disorders
BRADYPHRENIA
|
0.00%
0/44
|
6.7%
3/45
|
|
Psychiatric disorders
DEPRESSION
|
6.8%
3/44
|
4.4%
2/45
|
|
Psychiatric disorders
INSOMNIA
|
6.8%
3/44
|
6.7%
3/45
|
|
Respiratory, thoracic and mediastinal disorders
COUGH
|
6.8%
3/44
|
8.9%
4/45
|
|
Respiratory, thoracic and mediastinal disorders
DYSPNOEA EXERTIONAL
|
18.2%
8/44
|
13.3%
6/45
|
|
Respiratory, thoracic and mediastinal disorders
EPISTAXIS
|
6.8%
3/44
|
2.2%
1/45
|
|
Respiratory, thoracic and mediastinal disorders
DYSPNOEA
|
6.8%
3/44
|
4.4%
2/45
|
|
Skin and subcutaneous tissue disorders
DERMATITIS ACNEIFORM
|
52.3%
23/44
|
2.2%
1/45
|
|
Skin and subcutaneous tissue disorders
DRY SKIN
|
22.7%
10/44
|
4.4%
2/45
|
|
Skin and subcutaneous tissue disorders
ECZEMA
|
11.4%
5/44
|
2.2%
1/45
|
|
Skin and subcutaneous tissue disorders
ERYTHEMA
|
9.1%
4/44
|
2.2%
1/45
|
|
Skin and subcutaneous tissue disorders
EXFOLIATIVE RASH
|
6.8%
3/44
|
2.2%
1/45
|
|
Skin and subcutaneous tissue disorders
HAIR COLOUR CHANGES
|
9.1%
4/44
|
0.00%
0/45
|
|
Skin and subcutaneous tissue disorders
NIGHT SWEATS
|
6.8%
3/44
|
8.9%
4/45
|
|
Skin and subcutaneous tissue disorders
PALMAR-PLANTAR ERYTHRODYSAESTHESIA SYNDROME
|
11.4%
5/44
|
0.00%
0/45
|
|
Skin and subcutaneous tissue disorders
PRURITUS
|
6.8%
3/44
|
4.4%
2/45
|
|
Skin and subcutaneous tissue disorders
SKIN CHAPPED
|
9.1%
4/44
|
0.00%
0/45
|
|
Skin and subcutaneous tissue disorders
SKIN FISSURES
|
6.8%
3/44
|
0.00%
0/45
|
|
Vascular disorders
HYPERTENSION
|
18.2%
8/44
|
2.2%
1/45
|
|
Vascular disorders
LYMPHOEDEMA
|
25.0%
11/44
|
4.4%
2/45
|
|
Skin and subcutaneous tissue disorders
ALOPECIA
|
13.6%
6/44
|
4.4%
2/45
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place