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

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ClinicalTrials.gov Identifier: NCT02402842
Recruitment Status : Active, not recruiting
First Posted : March 30, 2015
Last Update Posted : October 6, 2017
Sponsor:
Information provided by (Responsible Party):
Centre Hospitalier Universitaire de Besancon

Brief Summary:

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.


Condition or disease Intervention/treatment Phase
Anal Canal Carcinoma Drug: Docetaxel, Cisplatin and 5-Fluorouracil Phase 2

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  (Clinical Trial)
Actual Enrollment : 70 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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.
Study Start Date : September 2014
Estimated Primary Completion Date : September 2018
Estimated Study Completion Date : September 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Anal Cancer
U.S. FDA Resources

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.



Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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. 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

  5. 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

  6. 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



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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02402842


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

Publications:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Centre Hospitalier Universitaire de Besancon
ClinicalTrials.gov Identifier: NCT02402842     History of Changes
Other Study ID Numbers: Epitopes-HPV02
2014-001789-81 ( EudraCT Number )
First Posted: March 30, 2015    Key Record Dates
Last Update Posted: October 6, 2017
Last Verified: October 2017

Keywords provided by Centre Hospitalier Universitaire de Besancon:
gastrointestinal oncology
immunology
taxane

Additional relevant MeSH terms:
Carcinoma
Anus Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Rectal Neoplasms
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Intestinal Diseases
Anus Diseases
Rectal Diseases
Docetaxel
Cisplatin
Fluorouracil
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antimetabolites
Antimetabolites, Antineoplastic
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs