Clinical and Biological Interest of Taxanes in Advanced Squamous Cell Anal Carcinoma

Anal Canal Carcinoma Clinical Trial

— Epitopes-HPV02  

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02402842
• Other study ID #: Epitopes-HPV02
• Secondary ID: 2014-001789-81
• Status: Completed
• Phase: Phase 2
• Start date: September 2014
• Est. completion date: June 30, 2020

Study information

• Verified date: May 2022
• Source: Centre Hospitalier Universitaire de Besancon
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 70
• Est. completion date: June 30, 2020
• Est. primary completion date: June 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Anal Canal Carcinoma
• Anus Neoplasms
• Carcinoma

Intervention

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.

Locations

Country	Name	City	State
France	University hospital of Besançon	Besançon
France	FNLCC center Georges François Leclerc	Dijon
France	Oscar Lambret center	Lille
France	Jean Mermoz Private Hospital	Lyon
France	Hospital of Belfort-Montbeliard	Montbeliard
France	Regional Institute of Cancer	Montpellier
France	Institute of Cancerology of Lorraine	Nancy
France	Antoine Lacassagne Center	Nice
France	Curie Institute	Paris
France	European Georges Pompidou Hospital	Paris
France	Mutualist Montsouris Institute	Paris
France	Paris Saint-Joseph Hospital Group	Paris
France	Pitié Salpétrière Hospital	Paris
France	Saint-Antoine Hospital	Paris
France	University Robert Debré Hospital	Reims
France	Paul Strauss Center	Strasbourg

Sponsors (1)

Lead Sponsor	Collaborator
Centre Hospitalier Universitaire de Besancon

Country where clinical trial is conducted

France, 

References & Publications (5)

Kim S, François E, André T, Samalin E, Jary M, El Hajbi F, Baba-Hamed N, Pernot S, Kaminsky MC, Bouché 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 — View Citation

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. — View Citation

Kim S, Meurisse A, Spehner L, Stouvenot M, François E, Buecher B, André T, Samalin E, Jary M, Nguyen T, El Hajbi F, Baba-Hamed N, Pernot S, Kaminsky MC, Bouché 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. — View Citation

Spehner L, Kim S, Vienot A, François 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). pii: E6838. doi: 10.3390/ijms21186838. — View Citation

Stouvenot M, Meurisse A, Saint A, Buecher B, André T, Samalin E, Jary M, El Hajbi F, Baba-Hamed N, Pernot S, Kaminsky MC, Bouché 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Overall survival	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)
Secondary	Progression free survival	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)
Secondary	response rate	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
Secondary	Tolerance of the DCF regimen ( Common Terminology Criteria for Adverse Events version 4.03)	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
Secondary	quality of life related to health	EORTC-QLQ-C30 & time to QoL score deterioration	from the inclusion to patient death or for maximum 3 years after end of treatment
Secondary	HPV-specific T cell responses measured by ELISPOT assay before and after DCF treatment	HPV-specific T cell responses measured by ELISPOT assay	at baseline (inclusion) and 4 weeks after the end of DCF regimen