Clinical and Biological Interest of Taxanes in Advanced Squamous Cell Anal Carcinoma (Epitopes-HPV02)

May 10, 2022 updated by: Centre Hospitalier Universitaire de Besancon

Assessment of the Clinical Value of a Docetaxel, Cisplatin and 5-fluorouracil (DCF) Strategy Adapted to Patients for the Management of Metastatic or Locally Advanced Anal Resistant Radiochemotherapy Squamous Cell Anal Carcinoma.

Squamous cell carcinoma of the anal canal (SCCA) is a rare disease and mostly diagnosed at an early stage. After standard concurrent chemoradiation (CRT) with mitomycin (MMC) and 5-fluorouracil (5FU), the disease will recur in 20% of patients. After treatment failure (including salvage surgery), cisplatin-5FU combination is the standard option but complete response is a rare event and the prognosis remains poor with most patients' death occurring in the first 12 months. Decision making for physicians in this setting is only based on retrospective studies or small phase II clinical trials including less than 20 patients. Hence, no efficient standard of care is currently available for relapsing SCCA patients who are currently treated with a palliative intent.

Between 2007 and 2013, 8 consecutive patients with advanced recurrent SCCA after CRT were treated with DCF regimen (docetaxel, cisplatin and 5-fluorouracil) in the Regional Cancer Institute of Franche Comté. After a median follow-up of 41 months, 4 patients (50%) achieved a complete response. Three patients underwent surgery of all involved metastatic sites. A pathological complete response was observed for all of them including in metastases occurring in irradiated fields, suggesting that taxane-based chemotherapy might be an effective strategy to circumvent resistance to radiotherapy (a preliminary cohort of 8 patients was published (Kim S et al Annals of oncology 2013). Furthermore, all complete responders were HPV 16, and high levels of specific T cell responses against Human Papillomavirus (HPV) HPV16-derived E6/E7 and telomerase were detected in 50% of complete responders suggesting the potential restoration of cancer immunosurveillance by this regimen.

Then, the Epitopes-HPV02 multicenter phase II study will aim to confirm the new role of taxane-based chemotherapy in SCCA patients.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Epitopes-HPV02 study is a national multicenter open label phase II trial including 66 patients.

Patients will receive 6 cycles of DCF regimen (docetaxel 75 mg/m2 day, CDDP 75 mg/m2 and 5FU at 750 mg/m2/day for 5 days) every 3 weeks or 8 cycles of modified-DCF regimen (docetaxel 40 mg/m2 day, CDDP 40 mg/m2 day and 5-FU at 1200 mg/m2/day for 2 days) every 2 weeks, according to their clinical status.

CT scan will be planned at baseline, after 3 and after 6 cycles of DCF regimen (or after 4 and 8 cycles of modified-DCF regimen) and then every three months until disease progression or death. A Pet-scan will be performed before and after 6 cycles of DCF. Tumor assessment will be carried out according to RECIST V1.1 criteria.

This study is carried out by the University Hospital of Besançon and were approved by the independent Est-II French Committee for Protection of Persons (CPP) and by the French Health Products Safety Agency (ANSM). This study will be conducted in 17 clinical centers in France.

Study Type

Interventional

Enrollment (Actual)

70

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Besançon, France, 25000
        • University Hospital of Besancon
      • Dijon, France, 21000
        • FNLCC center Georges François Leclerc
      • Lille, France, 59000
        • Oscar Lambret Center
      • Lyon, France, 69 008
        • Jean Mermoz Private Hospital
      • Montbeliard, France, 25200
        • Hospital of Belfort-Montbeliard
      • Montpellier, France, 34 298
        • Regional Institute of Cancer
      • Nancy, France, 54 519
        • Institute of Cancerology of Lorraine
      • Nice, France, 06 189
        • Antoine Lacassagne Center
      • Paris, France, 75 014
        • Paris Saint-Joseph Hospital Group
      • Paris, France, 75 248
        • Curie Institute
      • Paris, France, 75 651
        • Pitié Salpétrière Hospital
      • Paris, France, 75 674
        • Mutualist Montsouris Institute
      • Paris, France, 75 908
        • European Georges Pompidou Hospital
      • Paris, France, 75571
        • Saint-Antoine Hospital
      • Reims, France, 51 092
        • University Robert Debré Hospital
      • Strasbourg, France, 67 065
        • Paul Strauss Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Age ≥ 18 years
  • Performance status ECOG-WHO ≤ 1
  • histologically proved and unresectable locally advanced or metastatic squamous cell anal carcinoma
  • patient eligible to DCF regimen
  • signed written informed consent

Exclusion Criteria:

  • known hypersensitivity or contraindication to any of the study drugs (docetaxel, cisplatin, 5-fluorouracil).
  • previous chemotherapy for metastatic disease
  • previous chemotherapy by paclitaxel, docetaxel or navelbine
  • previous chemotherapy by cisplatin, except of concomitant radiotherapy
  • SIDA
  • clinically significant cardiac disease
  • other malignancy within the last 3 years, except for adequately treated carcinoma in situ of the cervix or squamous carcinoma of the skin, or adequately controlled limited basal cell skin cancer.
  • simultaneous participation in another clinical study
  • pregnancy, breast-feeding or absence of adequate contraception for fertile patients
  • patient with any medical or psychiatric condition or disease which would make the patient inappropriate for entry into this study.
  • patient under guardianship, curator or under the protection of justice.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: DCF regimen
docetaxel 75 mg/m2 day, Cisplatin75 mg/m2 and 5Fluorouracil at 750 mg/m2/day for 5 days
Drug: Docetaxel, Cisplatin and 5-Fluorouracil
Patients will receive 6 cycles of DCF regimen (docetaxel 75 mg/m2 day, cisplatin 75 mg/m2 and 5 Fluorouracil at 750 mg/m2/day for 5 days) every 3 weeks or 8 cycles of modified-DCF regimen (docetaxel 40 mg/m2 day, cisplatin 40 mg/m2 day and 5-Fluorouracil at 1200 mg/m2/day for 2 days) every 2 weeks, according to their clinical status.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression-free survival rate
Time Frame: 12 months after initiation of chemotherapy DCF.
Progression-free survival observed = the number of patients alive without progression at 12 months.
12 months after initiation of chemotherapy DCF.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall survival
Time Frame: date of death from any cause (within 3 years after the initiation of the treatment)
time between the date of initiation of treatment and the date of death from any cause.
date of death from any cause (within 3 years after the initiation of the treatment)
Progression free survival
Time Frame: date of first progression of the disease (within 3 years after the initiation of the treatment)
time interval between the date of initiation of treatment and the date of first progression (local, remote [extent of the disease by RECIST v1.1] second cancer) or death from any cause.
date of first progression of the disease (within 3 years after the initiation of the treatment)
response rate
Time Frame: 4 weeks after the end of DCF regimen
response rate will be evaluated using Response Evaluation Criteria in Solid Tumor (RECIST) v1.1 by CT-scan
4 weeks after the end of DCF regimen
Tolerance of the DCF regimen ( Common Terminology Criteria for Adverse Events version 4.03)
Time Frame: from the initiation of DCF regimen to 4 weeks after the end of DCF regimen
description of toxicities and adverse events according to Common Terminology Criteria for Adverse Events version 4.03
from the initiation of DCF regimen to 4 weeks after the end of DCF regimen
quality of life related to health
Time Frame: from the inclusion to patient death or for maximum 3 years after end of treatment
EORTC-QLQ-C30 & time to QoL score deterioration
from the inclusion to patient death or for maximum 3 years after end of treatment
HPV-specific T cell responses measured by ELISPOT assay before and after DCF treatment
Time Frame: at baseline (inclusion) and 4 weeks after the end of DCF regimen
HPV-specific T cell responses measured by ELISPOT assay
at baseline (inclusion) and 4 weeks after the end of DCF regimen

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Centre Hospitalier Universitaire de Besancon

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2014

Primary Completion (Actual)

June 1, 2018

Study Completion (Actual)

June 30, 2020

Study Registration Dates

First Submitted

November 27, 2014

First Submitted That Met QC Criteria

March 25, 2015

First Posted (Estimate)

March 30, 2015

Study Record Updates

Last Update Posted (Actual)

May 16, 2022

Last Update Submitted That Met QC Criteria

May 10, 2022

Last Verified

May 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Epitopes-HPV02
  • 2014-001789-81 (EudraCT Number)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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