- This is a randomised multi-centre study. 80 patients (forty in each of 2 arms) with melanoma will be randomly assigned to receive treatment with paclitaxel chemotherapy or the same drug along with GSK1120212, a new medicine. To take part the patient's melanoma must have a normal BRAF gene (at V600), which is about 60% of people with melanoma. This can be checked on a sample of the patient's tumour (usually one that has already been taken as part of their treatment). Prior to the randomised part of the study, between 9 and 18 patients will take part in the trial to establish the best dose of GSK1120212 and paclitaxel in combination.
More details can be found at http://public.ukcrn.org.uk/Search/StudyDetail.aspx?StudyID=12095
Randomised interventional phase II trial
Dose Escalation Phase: Patients with advanced melanoma will be recruited into 3 dose level cohorts. Three dose levels of GSK1120212, starting at 1.0mg for the first cohort and escalating by 0.5 mg to 1.5mg and 2.0mg for the second and third cohorts respectively. At all dose levels, GSK1120212 will be administered once daily orally in combination with an 80mg/m2 IV infusion of paclitaxel on Days 1, 8 and 15 of each 4 week cycle. This phase will determine the maximum tolerated dose of GSK1120212 in combination with paclitaxel for the randomisation phase. Paclitaxel will be administered for up to 6 cycles, but GSK1120212 may be continued until disease progression or intolerable toxicity.
Randomisation Phase: Two treatment arms; Maximum 6 cycles of single agent Paclitaxel alone as an 80mg/m2 IV infusion on Days 1, 8 and 15 of each 4 week cycle or
Maximum 6 cycles of Paclitaxel as an 80mg/m2 IV infusion on Days 1, 8 and 15 of each 4 week cycle in combination with maximum tolerated dose of GSK1120212 once daily orally.
GSK1120212 may be continued until disease progression or intolerable toxicity.
Patients will be followed up every 3 months until disease progression.
- 1. Efficacy of GSK1120212 in combination with paclitaxel compared to paclitaxel alone
- 2. Progression free survival
- 1. Further efficacy of GSK1120212 in combination with paclitaxel compared to paclitaxel alone
- 2. Overall survival
- 3. Objectine response rate
- 4. Progression free survival at 6 months
Sorry, this information is not available
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UK Sample Size: 98 - a max of 18 patients will be recruited to the dose escalation phase to determine the max tolerated dose. 80 patients will be recruited into the randomised phase II study
- 1. Aged = 18 years
- 2. Able to provide evidence from an accredited laboratory of wt BRAF status for their melanoma, or ascertainment of wild type 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
- 11. Target Gender: Male & Female
- 12. Lower Age Limit 18 years
- 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 intraocular pressure, glaucoma, uncontrolled hypertension or uncontrolled diabetes.
A randomised phase II study of paclitaxel with or without GSK1120212 in advanced wild type BRAF melanoma
University of Oxford (UK)