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

Sponsor

Centre Hospitalier Universitaire de Besancon (Other)

Overall Status

Completed

CT.gov ID

NCT02402842

Collaborator

(none)

Enrollment

Locations

Arm

69.9

Duration (Months)

4.4

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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 Design

Study Type:

Interventional

Actual Enrollment :

70 participants

Allocation:

N/A

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 :

Sep 1, 2014

Actual Primary Completion Date :

Jun 1, 2018

Actual Study Completion Date :

Jun 30, 2020

Arms and Interventions

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.

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.

Outcome Measures

Primary Outcome Measures

Progression-free survival rate [12 months after initiation of chemotherapy DCF.]
Progression-free survival observed = the number of patients alive without progression at 12 months.

Secondary Outcome Measures

Overall survival [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.
Progression free survival [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.
response rate [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
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]
description of toxicities and adverse events according to Common Terminology Criteria for Adverse Events version 4.03
quality of life related to health [from the inclusion to patient death or for maximum 3 years after end of treatment]
EORTC-QLQ-C30 & time to QoL score deterioration
HPV-specific T cell responses measured by ELISPOT assay before and after DCF treatment [at baseline (inclusion) and 4 weeks after the end of DCF regimen]
HPV-specific T cell responses measured by ELISPOT assay

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	University hospital of Besançon	Besançon	France	25000
2	FNLCC center Georges François Leclerc	Dijon	France	21000
3	Oscar Lambret center	Lille	France	59000
4	Jean Mermoz Private Hospital	Lyon	France	69 008
5	Hospital of Belfort-Montbeliard	Montbeliard	France	25200
6	Regional Institute of Cancer	Montpellier	France	34 298
7	Institute of Cancerology of Lorraine	Nancy	France	54 519
8	Antoine Lacassagne Center	Nice	France	06 189
9	Paris Saint-Joseph Hospital Group	Paris	France	75 014
10	Curie Institute	Paris	France	75 248
11	Pitié Salpétrière Hospital	Paris	France	75 651
12	Mutualist Montsouris Institute	Paris	France	75 674
13	European Georges Pompidou Hospital	Paris	France	75 908
14	Saint-Antoine Hospital	Paris	France	75571
15	University Robert Debré Hospital	Reims	France	51 092
16	Paul Strauss Center	Strasbourg	France	67 065