Immunomonitoring and Biomarker Research in Patients With Squamous Cell Anal Carcinoma

NCT ID: NCT03942900

Last Updated: 2021-07-30

Basic Information

• Recruitment Status: WITHDRAWN
• Study Classification: OBSERVATIONAL
• Study Start Date: 2020-04-01
• Study Completion Date: 2024-04-30

Brief Summary

Even if squamous cell carcinoma of the anal canal (SCCA) is a rare disease, its incidence increases worldwide. SCCA is mostly induced by Human papillomavirus (HPV) infections and HPV-related oncoproteins (E6 and E7) are expressed in more than 90% of SCCA. T stage and N stage are recognized prognostic factors for local and/or distant recurrence in SCCA patients treated by chemoradiotherapy. In fact, ≥T3 or ≥N1 anal cancers are associated with as high as 50% of disease recurrence rate at 2 years.

The University Hospital of Besançon with the Gercor conducted a prospective clinical trial (Epitopes HPV02 study) including 69 advanced SCCA patients and established a new standard of care based on Docetaxel, Cisplatin and 5-FU (5-FluoroUracil) chemotherapy (DCF). Among 69 patients treated with DCF regimen, 66 patients were evaluable for efficacy end-points. The objective response rate was 86% including 44% of complete response, and 47% of patients were progression-free at 12 months of follow-up from the first cycle of DCF treatment. Thus, the "Epitopes-HPV02" trial has demonstrated a high response rate of the DCF regimen with a higher than expected 12 months progression-free survival rate.These results raised the hypothesis of DCF being an immunogenic chemotherapy and in that demonstrating a possibly new role of taxane-based chemotherapy in SCCA patients. More than 50% of patients in complete remission had a detectable immunological response against peptides derived from HPV oncoproteins (E6 or E7) or from the telomerase antigen (which is transactivated by E6).

LAND study will enroll patients with locally advanced SCCA enrolled in OPTIMANAL clinical trial. OPTIMANAL study will assess the feasibility and efficacy to combine nivolumab to mDCF chemotherapy, followed by the standard chemo-radiotherapy, in high risk locally advanced SCCA patients with T3/T4 N1a or N1b/N1c disease.

LAND study is an exploratory translational study, which will analyze the biological mechanisms of action and our ability to track the immune responses against HPV and telomerase. The investigator group will take advantage of the presence of HPV antigens in most patients to set up a specific immunomonitoring program based on tumor samples and blood-derived lymphocytes to better understand the potential synergisms between immunogenic chemotherapy and anti-PD1 (Programmed Death-1), and to identify valuable biomarkers of treatment efficacy.

Conditions

Anal Canal Cancer

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

Cohort LAND

Patients enrolled in OPTIMANAL clinical trial

Additional biological samples

Intervention Type: OTHER

• Biomonitoring blood sample will be collected: 6 EDTA tubes (6 mL) for PBMC (peripheral blood mononucleated cell), 1 EDTA tube (6 mL) for plasma freezing and 2 EDTA tubes (4 mL) for ctDNA:

• at baseline,
• at first tumor assessment (phase 2 in OPTIMANAL study),
• at second tumor assessment (phase 4 in OPTIMANAL study),
• at end-point visit.
• A tumor biopsy or archived tumor sample will be mandatory at baseline.

Interventions

Additional biological samples

• Biomonitoring blood sample will be collected: 6 EDTA tubes (6 mL) for PBMC (peripheral blood mononucleated cell), 1 EDTA tube (6 mL) for plasma freezing and 2 EDTA tubes (4 mL) for ctDNA:

• at baseline,
• at first tumor assessment (phase 2 in OPTIMANAL study),
• at second tumor assessment (phase 4 in OPTIMANAL study),
• at end-point visit.
• A tumor biopsy or archived tumor sample will be mandatory at baseline.

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

1. Male or female, age ≥18 years,

2. Patients enrolled in OPTIMANAL trial

3. Signed and dated informed consent for LAND-translational study

4. Histologically proved squamous cell anal carcinoma.

Exclusion Criteria

1. Patient with any medical or psychiatric condition or disease, which would make the patient inappropriate for entry into this study,

2. Patient under guardianship, curators or under the protection of justice.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Centre Hospitalier Universitaire de Besancon

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Christophe BORG, Pr

Role: STUDY_DIRECTOR

CHU Besançon

Locations

Centre Hospitalier Universitaire de Besançon

Besançon, , France

Hôpital Nord Franche-Comté

Montbéliard, , France

Countries

France

References

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.

Reference Type: BACKGROUND

PMID: 28841909 (View on PubMed)

Bernard-Tessier A, Jeannot E, Guenat D, Debernardi A, Michel M, Proudhon C, Vincent-Salomon A, Bieche I, Pierga JY, Buecher B, Meurisse A, Francois E, Cohen R, Jary M, Vendrely V, Samalin E, El Hajbi F, Baba-Hamed N, Borg C, Bidard FC, Kim S. Clinical Validity of HPV Circulating Tumor DNA in Advanced Anal Carcinoma: An Ancillary Study to the Epitopes-HPV02 Trial. Clin Cancer Res. 2019 Apr 1;25(7):2109-2115. doi: 10.1158/1078-0432.CCR-18-2984. Epub 2018 Nov 30.

Reference Type: BACKGROUND

PMID: 30504426 (View on PubMed)

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.

Reference Type: RESULT

PMID: 30042063 (View on PubMed)

Other Identifiers

P/2018/381

Identifier Type: -

Identifier Source: org_study_id