Docetaxel with or without AZD6244 in wt BRAF advanced melanoma

ISRCTN ISRCTN89118367
DOI https://doi.org/10.1186/ISRCTN89118367
EudraCT/CTIS number 2009-018153-23
ClinicalTrials.gov number NCT01256359
Secondary identifying numbers 8672
Submission date
29/10/2010
Registration date
29/10/2010
Last edited
26/10/2022
Recruitment status
No longer recruiting
Overall study status
Completed
Condition category
Cancer
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data

Plain English summary of protocol

https://www.cancerresearchuk.org/about-cancer/find-a-clinical-trial/a-trial-docetaxel-with-without-AZD6244-advanced-melanoma

Contact information

Ms Linda Collins
Scientific

Old Road Campus
Roosevelt Drive
Headington
Oxford
OX3 7DQ
United Kingdom

Email Linda.Collins@clinpharm.ox.ac.uk

Study information

Study designMulticentre randomised interventional treatment trial
Primary study designInterventional
Secondary study designRandomised controlled trial
Study setting(s)Hospital
Study typeTreatment
Participant information sheet Not available in web format, please use the contact details below to request a patient information sheet
Scientific titleDocetaxel +/- AZD6244 in Melanoma - A double blind randomised phase 2 trial of docetaxel with or without AZD6244 in wt BRAF advanced melanoma
Study acronymDOC-MEK
Study objectivesThis is a randomised, double-blind placebo controlled phase 2 trial. Patient will be randomly assigned 1:1 between two treatment arms. They will receive either docetaxel 75 mg/m^2 intravenously (IV) and placebo given twice daily (bd), or AZD6244 75 mg bd daily with docetaxel 75 mg/m^2 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 electrocardiogram (ECG) will be performed at screening. Disease assessment will be by computed tomography (CT) scanning using modified Response Evaluation Criteria in Solid Tumours (RECIST) criteria after 9 and 18 weeks, then every 3 months until disease progression.
Ethics approval(s)Oxfordshire REC A approved on 30/09/2010 (ref: 10/H0604/59)
Health condition(s) or problem(s) studiedTopic: National Cancer Research Network; Subtopic: Melanoma; Disease: Melanoma
InterventionPatients will receive 75 mg AZD6244 or placebo orally twice a day on a continuous schedule. Capsules should be taken whole and not opened or crushed. They should be taken on an empty stomach (no food or drink for 2 hours before or 1 hour after treatment), with approximately 240 ml of water. Doses should be taken approximately 12 hours apart. Wherever possible doses should not be missed but if a dose is missed then the next dose should be taken at the allotted time.

Docetaxel arm: Patients will receive docetaxel 75 mg/m2, rounded to the nearest 10 mg, based on the most recent body surface area, as a 1-hour IV infusion in 250 ml of either 5% glucose solution or 0.9% sodium chloride solution. Standard pre-medication with steroids should be given, consisting of dexamethasone 8 mg b.d. for 3 days starting 1 day prior to docetaxel administration. Treatment will be given on day 1 and every 3 weeks for up to 6 cycles. The dose of docetaxel may be reduced or delayed if necessary.
Intervention typeDrug
Pharmaceutical study type(s)
PhasePhase II
Drug / device / biological / vaccine name(s)Docetaxel, AZD6244
Primary outcome measureProgression free survival, assessed at end of trial
Secondary outcome measuresAssessed at end of trial:
1. Immunohistochemistry of proteins in the MAPkinase pathway
2. Genotyping of tumours
3. Adverse events using CTCAE v4.0
4. Vital signs and weight
5. Biochemistry, haematology and urinalysis
6. Overall survival (OS)
7. Objective response rate (ORR)
8. Progression free survival at 6 months (PFS)
Overall study start date13/10/2010
Completion date30/10/2011

Eligibility

Participant type(s)Patient
Age groupAdult
SexBoth
Target number of participantsPlanned sample size: 80
Total final enrolment83
Key inclusion criteria1. Aged greater than or equal to 16 years, either sex
2. 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
3. Unresectable stage 3 or 4, histologically proven cutaneous or unknown primary melanoma
4. At least 1 lesion, not previously irradiated, that can be accurately measured on CT or magnetic resonance imaging (MRI) as defined by modified RECIST criteria
5. Eastern Cooperative Oncology Group (ECOG) performance score of 0 or 1
6. Life expectancy of at least 12 weeks
7. 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
8. Haematological and biochemical indices within the ranges shown below:
8.1. Haemoglobin (Hb) greater than 10 g/dL
8.2. White blood count (WBC) greater than 3 x 10^9/L
8.3. Platelet count greater than 100,000/µL
8.4. Absolute neutrophil count greater than 1.5 x 10^9/L
8.5. Serum bilirubin less than or equal to 1.2 x upper limit of normal (ULN)
8.6. Asparate aminotransferase (AST) (SGOT) or alanine aminotranferase (ALT) less than or equal to 2.5 x ULN
8.7. Lactate dehydrogenase (LDH) less than or equal to 2 x ULN
8.8. Creatinine clearance (Cockcroft-Gault) greater than 50 ml/min
Key exclusion criteria1. Any anti-cancer therapy (including radiotherapy and participation in other clinical trials) within 28 days prior to Day 1
2. Prior DNA damaging agents or cytotoxic chemotherapy for metastatic melanoma
3. Any unresolved toxicity from prior anti-cancer therapy that is greater than CTCAE grade 2
4. 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 greater than 12 months, bilateral oophrectomy or hysterectomy).
5. Grade greater than or equal to 2 peripheral neuropathy at study entry
6. Patients of reproductive potential who are not willing to use adequate contraceptive measures for the duration of the study (both male and female patients)
7. Known severe hypersensitivity reactions to docetaxel or other drugs formulated in polysorbate 80
8. Ocular or mucosal malignant melanoma
9. Another active malignancy within the past five years
10. 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
11. Clinically significant and uncontrolled major medical condition(s): such as active infection, bleeding diathesis
12. Patients who are known to be serologically positive for hepatitis B, hepatitis C or human immunodeficiency virus (HIV)
13. Cardiac conditions, including uncontrolled hypertension (blood pressure [BP] greater than 160/100 despite treatment), heart failure New York Heart Association (NYHA) class 2 or above, prior or current cardiomyopathy, myocardial infarction within 6 months or angina requiring nitrate therapy more than once a week
14. Previous treatment with EGFR, ras, raf or MEK inhibitors
15. Inability to swallow capsules, refractory nausea and vomiting, chronic gastrointestinal diseases (e.g., inflammatory bowel disease) or significant bowel resection that would preclude adequate absorption
16. Taking medication that significantly induces or inhibits CYP3A4
Date of first enrolment13/10/2010
Date of final enrolment30/10/2011

Locations

Countries of recruitment

  • England
  • United Kingdom

Study participating centre

Old Road Campus
Oxford
OX3 7DQ
United Kingdom

Sponsor information

Oxford University (UK)
University/education

Wellcome Trust Centre for Human Genetics
Roosevelt Drive
Oxford
OX3 7BN
England
United Kingdom

Website http://www.well.ox.ac.uk/home
ROR logo "ROR" https://ror.org/052gg0110

Funders

Funder type

Industry

AstraZeneca UK Limited (UK)

No information available

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to shareNo
IPD sharing plan summaryNot provided at time of registration
Publication and dissemination planNot provided at time of registration
IPD sharing planNot provided at time of registration

Study outputs

Output type Details Date created Date added Peer reviewed? Patient-facing?
Results article results 01/05/2014 Yes No
Plain English results 26/10/2022 No Yes
HRA research summary 28/06/2023 No No

Editorial Notes

25/10/2022: Cancer Research UK plain English results link and total final enrolment added.
06/09/2019: ClinicalTrials.gov number added.