A Double Blind Randomised Phase 2 Trial of Docetaxel With or Without AZD6244 in wt BRAF Advanced Melanoma
- 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
- 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
- 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
- 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
- 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
- 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
- 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.