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A randomised phase 2 study of paclitaxel with or without GSK1120212 or pazopanib in advanced wt BRAF melanoma - Paclitaxel +/- GSK1120212 or pazopanib in Melanoma

Phase 1
Conditions
Advanced/metastatic melanoma
MedDRA version: 19.0Level: LLTClassification code 10027481Term: Metastatic melanomaSystem Organ Class: 100000004864
Therapeutic area: Diseases [C] - Cancer [C04]
Registration Number
EUCTR2011-002545-35-DE
Lead Sponsor
niversity of Oxford
Brief Summary

Not available

Detailed Description

Not available

Recruitment & Eligibility

Status
ot Recruiting
Sex
All
Target Recruitment
138
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. Adequate cardiac function (NYHA 0-1), and LVEF within normal limits on echocardiogram.

8. 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.

9. 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

1. Any systemic anti-cancer therapy (including participation in other clinical trials) within 28 days prior to Day 1 (42 days prior for ipilimumab).

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 or increased risk of bleeding and gastrointestinal abnormalities that may increase the risk for gastrointestinal bleeding

13. Poorly controlled hypertension

14. Major surgery or trauma within 28 days prior to first dose of treatment

15. Patients who are known to be serologically positive for Hepatitis B, Hepatitis C or HIV.

16. Inability to swallow tablets, refractory nausea and vomiting, chronic gastrointestinal diseases (eg, inflammatory bowel disease) or significant bowel resection that would preclude adequate absorption of GSK1120212 or pazopanib

17. Ocular disease predisposing to central serous retinopathy and/or retinal vein occlusion, including increased intra-ocular pressure, glaucoma, uncontrolled hypertension or uncontrolled diabetes.

18. Corrected QT interval (QTc) > 480 msecs or recent history of ischaemic heart disease/peripheral vascular disease/cerebrovascular disease

Study & Design

Study Type
Interventional clinical trial of medicinal product
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
Secondary Outcome Measures
NameTimeMethod
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