Docetaxel, Cisplatin, and 5-fluorouracil (DCF) chemotherapy in the treatment of metastatic or unresectable locally recurrent anal squamous cell carcinoma: a phase II study of French interdisciplinary GERCOR and FFCD groups (Epitopes-HPV02 study)

Abstract

Background: The squamous cell carcinoma of the anus (SCCA) is a rare disease, but its incidence is markedly increasing. About 15% of patients are diagnosed at metastatic stage, and more than 20% with a localized disease treated by chemoradiotherapy (CRT) will recur. In advanced SCCA, cisplatin and 5-fluorouracil (CF) combination is the standard option but complete response is a rare event and the prognosis remains poor with most disease progression occurring within the first 12 months. We have previously published the potential role of the addition of docetaxel (D). Among 8 consecutive patients with advanced recurrent SCCA after CRT, the DCF regimen induced a complete response in 4 patients, including 3 pathological complete responses. Then, the Epitopes-HPV02 study was designed to confirm the interest of DCF regimen in SCCA patients.

Methods: This multicentre phase II trial assesses the DCF regimen in advanced SCCA patients. Main eligibility criteria are: histologically proven SCCA, unresectable locally advanced recurrent or metastatic disease, Eastern Cooperative Oncology Group-performance status (ECOG-PS) <2, and being eligible for DCF. Patients receive either 6 cycles of standard DCF or 8 cycles of modified DCF depending on age (> vs. ≤ 75 years-old) and ECOG-PS (0 vs. 1). The trial was set up based on a Simon's optimal two-stage design for phase II trials, allowing an early futility interim analysis. The primary endpoint is the observed progression-free survival (PFS) rate at 12 months from the first DCF cycle. A PFS rate below 10% is considered uninteresting, while a PFS rate above 25% is expected. With a unilateral alpha error of 5% and a statistical power of 90%, 66 evaluable patients should be included. Main secondary endpoints are overall survival, PFS, response rate, safety, health-related quality of life, and the correlation of biomarkers with treatment efficacy.

Discussion: Since the recommended CF regimen is based in a small retrospective analysis and generates a low rate of complete responses, the Epitopes-HPV02 study will establish a new standard in case of a positive result. Associated biomarker studies will contribute to understand the underlying mechanism of resistance and the role of immunity in SCCA.

Trial registration: NCT02402842 , EudraCT: 2014-001789-81.

Keywords: Advanced; Anal carcinoma; And chemotherapy; Docetaxel; Metastatic.

Conflict of interest statement

Ethics approval and consent to participate

This trial is performed in conformity with the French public health law n° 2004–806 of August 9th 2004 concerning the biomedical researches, and with the regulatory decree n° 2006–477 of April 26th 2006. The investigators and the promoter compromise themselves to follow the good clinical practice (GCP) recommendations on biomedical researches on pharmaceuticals for human use, as mentioned in the article L. 1121–3 of public health law and the ministerial order of April 23rd 2004.

Before the start of the study, each patient is informed by the investigator, in writing as well as verbally, about the nature and implications of the proposed study, and chiefly of the possible benefits and risks for their health, having this notice been previously approved by the Committee for the Protection of Persons. The patients then have at least 48 h for reflexion on the topic. Consequently, the patients document their approval by signing the informed consent form before any intervention or procedure specified in the protocol. Both, the investigator and the patient, sign the consent form, and each part saves one example.

The study was approved by the independent “Est-II French Committee for Protection of Persons” (June 6, 2014) and by the French Health Products Safety Agency (July 15, 2014). The University Hospital of Besançon is the legal sponsor of this trial. The trial was registered at the European Clinical Trials database (EudraCT: 2014–001789-81; April 24, 2014). Thus, the trial has fully completed all required procedures to start patient enrolment in France. The first center was activated in September 17, 2014. The trial was then registered at The originals of all central documents of the study will be placed in an archive at the major study center for at least 15 years, including a patient identification list, the original data of medical source records, the original signed informed consent forms and copies of the general study documentation, adverse-event declarations and source documents, as well as treatment prescription information. These documents will be available for evaluation and/or audits by competent authorities and the promoter.

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

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