DOC-MEK

A double blind randomised phase 2 trial of docetaxel with or without AZD6244 in wt BRAF advanced melanoma.

STUDY STATUS

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.

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.

OBJECTIVES

Primary:

• To assess the efficacy of AZD6244 in combination with docetaxel, compared with docetaxel alone, in first line patients with wild type BRAF advanced malignant melanoma.

Secondary:

• To further assess the efficacy of AZD6244 in combination with docetaxel, compared with docetaxel alone, in first line patients with wild type BRAF advanced malignant melanoma.
• To assess the safety and tolerability of AZD6244 in combination with docetaxel compared with docetaxel alone.

• To assess the impact of tumour characteristics on response to docetaxel therapy with or without AZD6244.

 

Oncology Clinical Trials Office (OCTO)

Randomisation Service Mon-Fri 9-5 (UK Time):

UK Tel: 0800 389 1635, UK Fax: 0800 389 1629 (24hrs)

Non UK Tel: +44 (0)1865 617 014, Non UK Fax: +44 (0)1865 617 015 (24hrs)

 

General Enquiries: Tel: +44 (0)1865 617 000, Fax: +44 (0)1865 617 010

Email: DOC-MEK@octo-oxford.org.uk

Website: www.octo-oxford.org.uk