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

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ClinicalTrials.gov Identifier: NCT03942900
Recruitment Status : Not yet recruiting
First Posted : May 8, 2019
Last Update Posted : July 24, 2019
Sponsor:
Information provided by (Responsible Party):
Centre Hospitalier Universitaire de Besancon

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.


Condition or disease Intervention/treatment
Anal Canal Cancer Other: Additional biological samples

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Study Type : Observational
Estimated Enrollment : 59 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Immunomonitoring and Biomarker Research Based on Tumor and Blood Samples in Patients With Squamous Cell Anal Carcinoma
Estimated Study Start Date : September 2019
Estimated Primary Completion Date : September 2023
Estimated Study Completion Date : April 2024

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Anal Cancer

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.




Primary Outcome Measures :
  1. 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.


Biospecimen Retention:   Samples With DNA
  • A tumor biopsy or archived tumor sample will be mandatory at baseline. Tumor samples will be collected for HPV, p53 testing and translational research.
  • Biomonitoring blood sample will be collected: 6 EDTA (ethylenediaminetetraacetic acid) tubes (6 mL) for PBMC, 1 EDTA tube (6 mL) for plasma freezing and 2 EDTA tubes (4 mL) for circulating tumor DNA (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


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03942900


Contacts
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Contact: Stefano KIM, Dr 0381668166 stefanokim@gmail.com
Contact: Christophe BORG, Pr 0381668166 christophe.borg@efs.sante.fr

Locations
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France
Centre Hospitalier Universitaire de Besançon Not yet recruiting
Besançon, France
Contact: Stefano KIM, Dr         
Hôpital Nord Franche-Comté Not yet recruiting
Montbéliard, France
Contact: Christophe BORG, Pr         
Sponsors and Collaborators
Centre Hospitalier Universitaire de Besancon
Investigators
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Study Director: Christophe BORG, Pr CHU Besançon

Publications of Results:
Other Publications:
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Responsible Party: Centre Hospitalier Universitaire de Besancon
ClinicalTrials.gov Identifier: NCT03942900     History of Changes
Other Study ID Numbers: P/2018/381
First Posted: May 8, 2019    Key Record Dates
Last Update Posted: July 24, 2019
Last Verified: May 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Centre Hospitalier Universitaire de Besancon:
locally advanced SCCA
DCF
radiotherapy
nivolumab
biomarkers
Additional relevant MeSH terms:
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Anus Neoplasms
Neoplasms
Rectal Neoplasms
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Intestinal Diseases
Anus Diseases
Rectal Diseases