MelanomaPhase 2DOC-MEKNCT01256359
Docetaxel With or Without AZD6244 in Melanoma
A Phase 2 study testing Docetaxel and AZD6244 in people with Melanoma, run by University of Oxford at 1 site in United Kingdom.
Trial 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. Read more about this study
- Who is it for?
- Ages 16 years and older
- Conditions the study is for
- Melanoma
- What is being tested?
- Docetaxel and AZD6244
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 83 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Oct 2010to Feb 2020
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 16 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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)
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- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Double Blind Randomised Phase 2 Trial of Docetaxel With or Without AZD6244 in wt BRAF Advanced Melanoma
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.
Read the detailed description
No further information in addition to what has been provided in the brief summary
- Conditions
- Melanoma
- Being tested
- Docetaxel and AZD6244, Docetaxel and placebo
- Medical subject headings
- Melanoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Docetaxel and AZD6244Drug
Also called Taxotere
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.
Docetaxel and placeboDrug
Also called Taxotere
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.
| Study group | Role | What they receive |
|---|---|---|
| Docetaxel and AZD6244 | Experimental | Docetaxel with AZD6244 Receives: Drug: Docetaxel and AZD6244 |
| Docetaxel and Placebo | Experimental | Docetaxel without AZD6244 Receives: Drug: Docetaxel and placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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 (41)
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.
Measured: 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).
Measured: 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.
Measured: 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).
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Dec 2010 (estimated)
- Study startOct 2010
- Primary completionOct 2012
- Study completionFeb 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for MelanomaStudies of the same condition, open and under way.
- More trials run by University of OxfordThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 83 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Oxford
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Mark R Middleton, Principal investigator, University of Oxford
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01256359
- Sponsor's protocol ID
- OCTO_015
- Acronym
- DOC-MEK
- Status last verified
- Aug 2024
- First submitted
- 17 Nov 2010
- Last updated
- 15 Aug 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No