NCT02402842

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
70

participants targeted

Target at P50-P75 for phase_2

Timeline
Completed

Started Sep 2014

Longer than P75 for phase_2

Geographic Reach
1 country

16 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

September 1, 2014

Completed
3 months until next milestone

First Submitted

Initial submission to the registry

November 27, 2014

Completed
4 months until next milestone

First Posted

Study publicly available on registry

March 30, 2015

Completed
3.2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 1, 2018

Completed
2.1 years until next milestone

Study Completion

Last participant's last visit for all outcomes

June 30, 2020

Completed
Last Updated

May 16, 2022

Status Verified

May 1, 2022

Enrollment Period

3.8 years

First QC Date

November 27, 2014

Last Update Submit

May 10, 2022

Conditions

Anal Canal Carcinoma

Keywords

gastrointestinal oncologyimmunologytaxane

Outcome Measures

Primary Outcomes (1)

  • Progression-free survival rate

    Progression-free survival observed = the number of patients alive without progression at 12 months.

    12 months after initiation of chemotherapy DCF.

Secondary Outcomes (6)

  • Overall survival

    date of death from any cause (within 3 years after the initiation of the treatment)

  • Progression free survival

    date of first progression of the disease (within 3 years after the initiation of the treatment)

  • response rate

    4 weeks after the end of DCF regimen

  • Tolerance of the DCF regimen ( 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

    from the inclusion to patient death or for maximum 3 years after end of treatment

  • +1 more secondary outcomes

Study Arms (1)

DCF regimen

EXPERIMENTAL

docetaxel 75 mg/m2 day, Cisplatin75 mg/m2 and 5Fluorouracil at 750 mg/m2/day for 5 days

Drug: Docetaxel, Cisplatin and 5-Fluorouracil

Interventions

Docetaxel, Cisplatin and 5-FluorouracilDRUG

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.

DCF regimen

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (16)

University hospital of Besançon

Besançon, 25000, France

Location

FNLCC center Georges François Leclerc

Dijon, 21000, France

Location

Oscar Lambret center

Lille, 59000, France

Location

Jean Mermoz Private Hospital

Lyon, 69 008, France

Location

Hospital of Belfort-Montbeliard

Montbéliard, 25200, France

Location

Regional Institute of Cancer

Montpellier, 34 298, France

Location

Institute of Cancerology of Lorraine

Nancy, 54 519, France

Location

Antoine Lacassagne Center

Nice, 06 189, France

Location

Paris Saint-Joseph Hospital Group

Paris, 75 014, France

Location

Curie Institute

Paris, 75 248, France

Location

Pitié Salpétrière Hospital

Paris, 75 651, France

Location

Mutualist Montsouris Institute

Paris, 75 674, France

Location

European Georges Pompidou Hospital

Paris, 75 908, France

Location

Saint-Antoine Hospital

Paris, 75571, France

Location

University Robert Debré Hospital

Reims, 51 092, France

Location

Paul Strauss Center

Strasbourg, 67 065, France

Location

Related Publications (6)

  • Kim S, Jary M, Mansi L, Benzidane B, Cazorla A, Demarchi M, Nguyen T, Kaliski A, Delabrousse E, Bonnetain F, Letondal P, Bosset JF, Valmary-Degano S, Borg C. DCF (docetaxel, cisplatin and 5-fluorouracil) chemotherapy is a promising treatment for recurrent advanced squamous cell anal carcinoma. Ann Oncol. 2013 Dec;24(12):3045-50. doi: 10.1093/annonc/mdt396. Epub 2013 Oct 10.

    PMID: 24114858BACKGROUND

  • Kim S, Meurisse A, Spehner L, Stouvenot M, Francois E, Buecher B, Andre T, Samalin E, Jary M, Nguyen T, El Hajbi F, Baba-Hamed N, Pernot S, Kaminsky MC, Bouche O, Desrame J, Zoubir M, Ghiringhelli F, Parzy A, de la Fouchardiere C, Boulbair F, Lakkis Z, Klajer E, Jacquin M, Taieb J, Vendrely V, Vernerey D, Borg C. Pooled analysis of 115 patients from updated data of Epitopes-HPV01 and Epitopes-HPV02 studies in first-line advanced anal squamous cell carcinoma. Ther Adv Med Oncol. 2020 Dec 4;12:1758835920975356. doi: 10.1177/1758835920975356. eCollection 2020.

    PMID: 33329760BACKGROUND

  • Spehner L, Kim S, Vienot A, Francois E, Buecher B, Adotevi O, Vernerey D, Abdeljaoued S, Meurisse A, Borg C. Anti-Telomerase CD4+ Th1 Immunity and Monocytic-Myeloid-Derived-Suppressor Cells Are Associated with Long-Term Efficacy Achieved by Docetaxel, Cisplatin, and 5-Fluorouracil (DCF) in Advanced Anal Squamous Cell Carcinoma: Translational Study of Epitopes-HPV01 and 02 Trials. Int J Mol Sci. 2020 Sep 17;21(18):6838. doi: 10.3390/ijms21186838.

    PMID: 32957741BACKGROUND

  • Stouvenot M, Meurisse A, Saint A, Buecher B, Andre T, Samalin E, Jary M, El Hajbi F, Baba-Hamed N, Pernot S, Kaminsky MC, Bouche O, Desrame J, Zoubir M, Smith D, Ghiringhelli F, Parzy A, de la Fouchardiere C, Almotlak H, Vienot A, Jacquin M, Taieb J, Nguyen T, Vernerey D, Borg C, Kim S. Second-line treatment after docetaxel, cisplatin and 5-fluorouracil in metastatic squamous cell carcinomas of the anus. Pooled analysis of prospective Epitopes-HPV01 and Epitopes-HPV02 studies. Eur J Cancer. 2022 Feb;162:138-147. doi: 10.1016/j.ejca.2021.11.019. Epub 2022 Jan 4.

    PMID: 34995900BACKGROUND

  • Kim S, Francois E, Andre T, Samalin E, Jary M, El Hajbi F, Baba-Hamed N, Pernot S, Kaminsky MC, Bouche O, Desrame J, Zoubir M, Ghiringhelli F, Parzy A, De La Fouchardiere C, Smith D, Deberne M, Spehner L, Badet N, Adotevi O, Anota A, Meurisse A, Vernerey D, Taieb J, Vendrely V, Buecher B, Borg C. Docetaxel, cisplatin, and fluorouracil chemotherapy for metastatic or unresectable locally recurrent anal squamous cell carcinoma (Epitopes-HPV02): a multicentre, single-arm, phase 2 study. Lancet Oncol. 2018 Aug;19(8):1094-1106. doi: 10.1016/S1470-2045(18)30321-8. Epub 2018 Jul 2.

    PMID: 30042063RESULT

  • Kim S, Jary M, Andre T, Vendrely V, Buecher B, Francois E, Bidard FC, Dumont S, Samalin E, Peiffert D, Pernot S, Baba-Hamed N, El Hajbi F, Bouche O, Desrame J, Parzy A, Zoubir M, Louvet C, Bachet JB, Nguyen T, Abdelghani MB, Smith D, De La Fouchardiere C, Aparicio T, Bennouna J, Gornet JM, Jacquin M, Bonnetain F, Borg C. 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). BMC Cancer. 2017 Aug 25;17(1):574. doi: 10.1186/s12885-017-3566-0.

    PMID: 28841909DERIVED

MeSH Terms

Conditions

Anal Canal Carcinoma

Interventions

DocetaxelCisplatinFluorouracil

Intervention Hierarchy (Ancestors)

TaxoidsCyclodecanesCycloparaffinsHydrocarbons, AlicyclicHydrocarbons, CyclicHydrocarbonsOrganic ChemicalsDiterpenesTerpenesChlorine CompoundsInorganic ChemicalsNitrogen CompoundsPlatinum CompoundsUracilPyrimidinonesPyrimidinesHeterocyclic Compounds, 1-RingHeterocyclic Compounds

Study Design

Study Type
interventional
Phase
phase 2
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

November 27, 2014

First Posted

March 30, 2015

Study Start

September 1, 2014

Primary Completion

June 1, 2018

Study Completion

June 30, 2020

Last Updated

May 16, 2022

Record last verified: 2022-05

Locations

FR(16)