InterAACT: An international multicenter open label randomized phase II advanced anal cancer trial comparing cisplatin (CDDP) plus 5-fluorouracil (5-FU) versus carboplatin (CBDCA) plus weekly paclitaxel (PTX) in patients with inoperable locally recurrent (ILR) or metastatic disease.

Abstract

TPS792 Background: Metastatic squamous cell carcinoma of the anus (SCCA) is a rare condition with 5-year overall survival (OS) rate of 32%. CDDP/5-FU is commonly used in the first-line treatment of patients with ILR or metastatic disease. This practice is based on retrospective series and data from randomised trials are lacking. Recent retrospective studies showed promising activity of CBDCA/PTX in this setting. Methods: InterAACT is an international, multicentre, open label, randomised phase II trial comparing two chemotherapy regimens in patients with ILR or metastatic SCCA. Eligible patients are randomised in a 1:1 ratio to CDDP (60 mg/mq, D1q21) plus 5-FU (1000 mg/mq/24h, D1-4q21) or CBDCA (AUC 5, D1q28) plus PTX (80 mg/mq, D1,8,15q28). Stratification factors are: performance status, extent of disease, HIV status and country. The primary endpoint is response rate (RR). Secondary endpoints include progression-free survival, OS, toxicity and quality of life. Based on a RR estimate of 40% in the CDDP/5-FU arm 80 patients are to be recruited to detect 10% difference in RR between the two arms with 80% power (phase II selection trial design). Correlative biomarker analyses are planned in tumour tissue and blood samples. The trial is sponsored by The Royal Marsden NHS Foundation Trust and endorsed by the International Rare Cancer Initiative (IRCI) group. Approximately 50 centres in the UK, Europe (EORTC), Scandinavia, US (ECOG-ACRIN) and Australia (AGITG) are estimated to participate and recruitment is anticipated to be completed within 3 years. Recruitment started in December 2013. As of September 16, 2014, 6 sites in the UK are open to recruitment and 6 patients have been randomised (3 to CDDP/5-FU and 3 to CBDCA/PTX). InterAACT aims to provide the first randomised evidence for the treatment of ILR and metastatic SCCA, to identify the optimal chemotherapy backbone to combine with targeted agents in future studies and to confirm the feasibility of conducting an international multicentre trial for this rare tumour. Clinical trial information: NCT02051868.