Advanced/metastatic melanoma MedDRA version: 14.1 Level: LLT Classification code 10027481 Term: Metastatic melanoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Name: GSK1120212
Pharmaceutical Form: Tablet
CAS Number: 871700-17-3
Current Sponsor code: GSK1120212
Other descriptive name: tr
Sponsors
University of Oxford
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Aged = 18 years 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 (phase 2 part only). 3. Unresectable stage 3 or 4, histologically proven cutaneous or unknown primary melanoma 4. Measurable disease as defined by RECIST 1.1 (phase 2 part only). 5. ECOG performance score of 0 or 1. 6. Life expectancy of at least 12 weeks. 7. Maximum 2 prior lines of treatment for advanced disease. 8. Adequate cardiac function (NYHA 0-1), and LVEF within normal limits on echocardiogram. 9. 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. 10. Adequate haematological, hepatic and renal function. Are the trial subjects under 18? no Number of subjects for this age range: 0 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 0 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 0
Exclusion criteria
Exclusion criteria: 1. Any systemic anti-cancer therapy (including participation in other clinical trials) within 28 days prior to Day 1. 2. Any radiotherapy within 14 days prior to Day 1. 3. Prior taxane or BRAF or MEK inhibitors for metastatic melanoma. 4. Any unresolved toxicity from prior anti-cancer therapy that is greater than CTCAE grade 2. 5. 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). 6. Grade =2 peripheral neuropathy at study entry. 7. Patients of reproductive potential who are not willing to use adequate contraceptive measures for the duration of the study (both male and female patients) 8. Known severe hypersensitivity reactions to paclitaxel or other drugs formulated in Cremophor EL and ethanol 9. Ocular or mucosal malignant melanoma 10. Another active malignancy within the past three years. 11. 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. 12. Clinically significant and uncontrolled major medical condition(s): such as active infection, bleeding diathesis. 13. Patients who are known to be serologically positive for Hepatitis B, Hepatitis C or HIV. 14. Inability to swallow tablets, refractory nausea and vomiting, chronic gastrointestinal diseases (eg, inflammatory bowel disease) or significant bowel resection that would preclude adequate absorption. 15. Ocular disease predisposing to central serous retinopathy and/or retinal vein occlusion, including increased intra-ocular pressure, glaucoma, uncontrolled hypertension or uncontrolled diabetes.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Phase 1 - To establish the maximum tolerated dose of GSK1120212 in combination with paclitaxel in the treatment of patients with advanced melanoma. Phase 2 - To compare the efficacy of GSK1120212 in combination with paclitaxel, compared with paclitaxel alone in the treatment of patients with advanced or metastatic melanoma. ; Secondary Objective: To further assess the safety and efficacy of GSK1120212 in combination with paclitaxel, compared with paclitaxel alone in the treatment of patients with advanced or metastatic melanoma. To assess the impact of tumour characteristics on response to paclitaxel therapy with or without GSK1120212. ; Primary end point(s): Phase 1 component: Maximum tolerated dose of GSK1120212 in combination with paclitaxel Phase 2 component: Progression free survival | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Overall survival (OS). Objective response rate (ORR) Progression free survival at 6 months (PFS) Adverse events using CTCAE v4.0 Vital signs and weight Biochemistry, haematology and urinalysis Physical examination ECG | — |
Countries
Germany, United Kingdom
Outcome results
None listed