International Multicentre Study in Advanced Anal Cancer Comparing Cisplatin Plus 5 FU vs Carboplatin Plus Weekly Paclitaxel

Study design: This is an international, multicentre, open label, randomised phase II trial. Patients will be randomised to receive either cisplatin plus 5-FU or carboplatin plus weekly paclitaxel. Region (Europe, North America, South America \& Australia), (Eastern Cooperative Oncology Group- ECOG) ECOG performance status (PS) (0-1 vs. 2), HIV status (positive vs. negative) and extent of disease (locally recurrent vs. metastatic) will be used as stratification factors. Overall response rate is the primary endpoint. Indication: First line treatment of patients with inoperable locally recurrent or metastatic squamous cell carcinoma of the anus. Length of study: Recruitment should be completed within 3 years. The estimated recruitment rate is between 4-6 patients per month once it is established at multiple centres. Primary Objective: To evaluate best overall response rate by 24 weeks post treatment in the cisplatin plus 5-fluorouracil arm versus the carboplatin plus weekly paclitaxel arm Secondary Objectives: To evaluate: - Progression-free survival - Overall survival - Disease control rate (stable disease or better) at 12 and 24 weeks - Best overall response of metastatic lesions - Toxicity (graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE Version 4) - Quality of Life (using EORTC QLQ-C30 version 3 and EQ-5D-5L questionnaires). To assess: The feasibility of conducting a multicentre international study on squamous cell carcinoma of the anus and recruit within a reasonable time frame. Exploratory Objective: Explorative biomarker analysis including the collection of archived tumour tissue and blood sample at baseline and upon progression.