Docetaxel With or Without AZD6244 in Melanoma (DOC-MEK)

This is an interventional treatment trial for Melanoma Read More

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:

• 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.