Immunomonitoring and Biomarker Research in Patients With Squamous Cell Anal Carcinoma (LAND)

July 26, 2021 updated by: Centre Hospitalier Universitaire de Besancon

Immunomonitoring and Biomarker Research Based on Tumor and Blood Samples in Patients With Squamous Cell Anal Carcinoma

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.

Study Overview

Status

Withdrawn

Conditions

Intervention / Treatment

Study Type

Observational

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Besançon, France
        • CENTRE HOSPITALIER UNIVERSITAIRE de BESANCON
      • Montbéliard, France
        • Hôpital Nord Franche-Comté

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Probability Sample

Study Population

Patients with locally advanced squamous cell anal carcinoma enrolled in OPTIMANAL clinical trial, and given consent for LAND-translational study

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Cohort LAND
Patients enrolled in OPTIMANAL clinical trial
Other: 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Peripheral CD4 anti-telomerase immunity and MDSC (Myeloid-Derived Suppressor Cells) analysis
Time Frame: 24 months
Correlation of both peripheral CD4 anti-telomerase immunity and MDSC with progression-free survival.
24 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Centre Hospitalier Universitaire de Besancon

Investigators

  • Study Director: Christophe BORG, Pr, CHU Besançon

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ANTICIPATED)

April 1, 2020

Primary Completion (ANTICIPATED)

September 1, 2023

Study Completion (ANTICIPATED)

April 1, 2024

Study Registration Dates

First Submitted

May 7, 2019

First Submitted That Met QC Criteria

May 7, 2019

First Posted (ACTUAL)

May 8, 2019

Study Record Updates

Last Update Posted (ACTUAL)

July 30, 2021

Last Update Submitted That Met QC Criteria

July 26, 2021

Last Verified

July 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • P/2018/381

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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