Title

PACMEL

Chief Investigator: 

Sponsor: University of Oxford
EudraCT number: 2011-002545-35

A randomised phase 2 study of paclitaxel with or without GSK1120212 or pazopanib in advanced wt BRAF melanoma

Aim:

To evaluate, in a randomised phase 2 study, the efficacy of paclitaxel with or without the MEK inhibitor GSK1120212 (of which the most tolerable dose has been confirmed) or pazopanib in wild type BRAF metastatic melanoma, stratifying for NRAS mutation status.

Study Status

Open to recruitment:

  • Recruitment to the dose escalation phase was completed in February 2013.

  • Recruitment to the randomisation phase commenced in March 2013 and is currently underway with 76 patients recruited (April 2015).

Target recruitment: 120 patients to be recruited to the randomised phase by January 2016.
Number of active sites: 18 UK Sites and 7 German Sites (April 2015).

Inclusion Criteria

  • ≥ 18 years of age, written informed consent
  • Histologically confirmed, wild type BRAF, metastatic melanoma and able to provide a tumour sample for NRAS mutation testing
  • Unresectable Stage III or Stage IV metastatic melanoma.
  • Measurable disease as defined by RECIST 1.1.
  • Eastern Cooperative Oncology Group (ECOG) Performance Score of 0-1.
  • Adequate haematological, hepatic and renal function
  • Adequate cardiac function (NYHA 0-1), and LVEF within normal limits on echocardiogram.
  • Life expectancy > 12 weeks.
  • The patient is willing to give consent to the main study and be able to comply with the protocol for the duration of the study, including scheduled follow-up visits and examinations.

Exclusion Criteria

  • Any systemic anti-cancer therapy (including participation in other clinical trials) within 28 days prior to Day 1 (42 days prior for ipilimumab).
  • Any radiotherapy within 14 days prior to Day
  • Prior taxane or BRAF or MEK inhibitors 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 oophorectomy 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 paclitaxel or other drugs formulated in Cremophor EL and ethanol
  • Ocular or mucosal malignant melanoma
  • Another active malignancy within the past three 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 or increased risk of bleeding and gastrointestinal abnormalities that may increase the risk for gastrointestinal bleeding
  • Poorly controlled hypertension [defined as systolic blood pressure (SBP) of ≥140 mmHg or diastolic blood pressure (DBP) of ≥ 90mmHg].
  • Major surgery or trauma within 28 days prior to first dose of treatment
  • Patients who are known to be serologically positive for Hepatitis B, Hepatitis C or HIV.
  • Inability to swallow tablets, refractory nausea and vomiting, chronic gastrointestinal diseases (e.g. inflammatory bowel disease) or significant bowel resection that would preclude adequate absorption of GSK1120212 or pazopanib.
  • Ocular disease predisposing to central serous retinopathy and/or retinal vein occlusion, including increased intra-ocular pressure, glaucoma, uncontrolled hypertension or uncontrolled diabetes.
  • Corrected QT interval (QTc) > 480 msecs or recent history of ischaemic heart disease/peripheral vascular disease/cerebrovascular disease

Objectives

Primary:

  • Progression free survival

Secondary:

  • Objective response rate.
  • Progression free survival at 6 months
  • Safety of the GSK1120212/paclitaxel and pazopanib/paclitaxel combination
  • Overall survival.

Data Submission

Data submission for this trial is via electronic submission of data in OpenClinica. 

OpenClinica Training

OpenClinica is the world's leading open source clinical trial software for electronic data capture and clinical data management. 

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