BRAF mutation positive advanced cutaneous and unknown primary melanoma MedDRA version: 9.1 Level: LLT Classification code 10025654 Term: Malignant melanoma of sites other than skin MedDRA version: 9.1 Level: LLT Classification code 10025670 Term: Malignant melanoma stage III MedDRA version: 9.1 Level: LLT Classification code 10025671 Term: Malignant melanoma stage IV MedDRA version: 9.1 Level: LLT Classification code 10027152 Term: Melanoma of skin (malignant) MedDRA version: 9.1 Level: LLT
Conditions
Interventions
Product Name: AZD6244
Product Code: AZD6244
Pharmaceutical Form: Capsule, hard
CAS Number: 943332-08-9
Current Sponsor code: AZD6244
Other descriptive name: AZD6244
Concentration unit: mg milligram(s)
Sponsors
AstraZeneca AB
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Provision of signed, written and dated informed consent prior to any study specific procedures Male or female, aged 18 years or older Histological or cytological confirmation of advanced cutaneous or unknown primary melanoma WHO performance status 0 1 At least one lesion, not previously irradiated, that can be accurately measured at baseline as =10 mm in the longest diameter (LD; except lymph nodes which must have a short axis =15 mm) with CT or MRI, and which is suitable for accurate repeated measurements. Tumour sample confirmed as BRAF mutation positive (Note: sample must be available upon enrolment to ship to the AstraZeneca appointed central laboratory, or mutation status confirmed locally at an AstraZeneca agreed local laboratory using agreed methodology. Evidence of post-menopausal status, or negative urinary or serum pregnancy test for female pre-menopausal patients. Post menopausal status is defined as: -natural menopause with menses >1 year ago -radiation induced oophorectomy with last menses >1 year ago -chemotherapy-induced menopause with 1 year interval since last menses -serum FSH and LH and plasma oestradiol levels in the postmenopausal range for the institution -bilateral oophorectomy or hysterectomy Serum creatinine clearance >50 ml/min, by either Cockcroft-Gault formula or 24 hour urine collection analysis Patients should be able to swallow AZD6244/placebo capsules. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site) Previous randomization of treatment in the present study Having received an investigational drug within the 30 days prior to entry, or have not recovered from side effects of an investigational drug Diagnosis of uveal or mucosal melanoma Any prior Investigational therapy comprising inhibitors of Ras, Raf or MEK Any prior cytotoxic chemotherapy or biochemotherapy for advanced melanoma patients who previously received adjuvant biochemotherapy will be eligible, unless their treatment included temozolomide or dacarbazine Any other investigational non-chemotherapeutic therapy for advanced melanoma, with the exception of prior monotherapy with interleukin-2, cytokines (eg, a interferon or GM-CSF) or vaccine, which are permitted- use of anti-CTLA4 monoclonal antibodies will be allowed in adjuvant settings Any non-systemic therapy (except focal palliative radiotherapy) for advanced melanoma within 30 days of starting study treatment Any unresolved toxicity above CTCAE grade 2 from previous anti-cancer therapy, apart from alopecia Brain metastases or spinal cord compression unless treated and stable off treatment (eg, steroids) for at least 3 months Laboratory values as listed below (from laboratory results at Visit 1): -ANC 1.5xULN -AST or ALT >2.5xULN LDH =2xULN (from the Visit 1 laboratory result) Cardiac conditions as follows: -Uncontrolled hypertension (BP=150/95 despite optimal therapy) -Heart failure NYHA Class II or above -Prior or current cardiomyopathy -Baseline LVEF =50% -Atrial fibrillation with heart rate >100 bpm -Unstable ischaemic heart disease (myocardial infarction within 6 months prior to starting treatment, or angina requiring use of nitrates more than once weekly) Major surgery within 4 weeks prior to starting study treatment Hypersensitivity to AZD6244, or dacarbazine or any excipient of these agents Patients with a history of another primary malignancy within 5 years prior to starting study treatment, except adequately treated basal or squamous cell carcinoma of the skin, or carcinoma of the cervix in situ and the disease under study Any evidence of severe or uncontrolled systemic disease, active infection, active bleeding diathesis or renal transplant, including any patient known to have hepatitis B, hepatitis C or human immunodeficiency virus (HIV) Refractory nausea and vomiting, chronic gastrointestinal diseases (eg, inflammatory bowel disease), or significant bowel resection that would preclude adequate absorption Female patients who are breast-feeding or patients of reproductive potential who are not employing an effective method of birth control Clinical judgement by the investigator that the patient should not participate in the study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the efficacy in terms of Overall Survival (OS) of AZD6244 in combination with dacarbazine, compared with dacarbazine alone, in first line patients with BRAF mutation positive advanced cutaneous melanoma or unknown primary melanoma.;Secondary Objective: To further assess the efficacy of AZD6244 in combination with dacarbazine, compared with dacarbazine alone, in first line patients with BRAF mutation positive advanced cutaneous or unknown primary melanoma To assess the safety and tolerability profile of AZD6244 in combination with dacarbazine To investigate the use of plasma and serum as a potential source of circulating free tumour DNA (CFDNA) for the analysis of BRAF mutation status To investigate the pharmacokinetics of AZD6244 and N-desmethyl AZD6244 when AZD6244 is administered in combination with dacarbazine;Primary end point(s): Overall Survival | — |
Countries
Czech Republic, France, Germany, Hungary, Netherlands, Spain, Sweden, United Kingdom
Outcome results
None listed