Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

Predictive Biomarkers for Response to Nivolumab in Head and Neck Squamous Cell Carcinoma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03652142
Recruitment Status : Recruiting
First Posted : August 29, 2018
Last Update Posted : August 29, 2018
Sponsor:
Information provided by (Responsible Party):
AMANDA PSYRRI, Attikon Hospital

Brief Summary:

Nivolumab is FDA-approved for the treatment of patients with recurrent/metastatic Head and Neck Squamous Cell Carcinoma (HNSCC).

HNSCC whose disease has progressed within 6 months after platinum-based chemotherapy. The development of predictive biomarkers is needed to optimize patient benefit, minimize risk of toxicities and guide combination strategies.


Condition or disease Intervention/treatment
HNSCC DNA Damage DNA Double Strand Break Other: Biomarker Research Drug: Nivolumab

Detailed Description:

Nivolumab is FDA-approved for the treatment of patients with recurrent/metastatic Head and Neck Squamous Carcinoma (HNSCC) whose disease has progressed within 6 months after platinum-based chemotherapy. The development of predictive biomarkers is needed to optimize patient benefit, minimize risk of toxicities and guide combination strategies. The greatest focus has been on tumor-cell programmed death Ligand 1 (PD-L1) expression. Although PD-L1 positivity enriches for populations with clinical benefit, PD-L1 testing alone is insufficient for patient selection in most malignancies. PD-L1 expression can be transient, and intrapatient and even intratumor heterogeneity in PD- L1 tumor expression can exist. Therefore, tumor sampling at one timepoint might not accurately reflect the state of PD1 axis in a patient. Another important aspect is that PD-L1 immunohistochemistry alone does not take into account factors that could impede the anti-PD1 therapy response such as whether or not active immune cell engagement of the PD1 axis occurs in the tumor microenvironment or other concurrent immune suppressive pathways are present.

Assessment of biomarkers at baseline may not predict benefit from immunotherapy. In a phase II study of ipilimumab in patients with metastatic melanoma baseline tumor infiltrating lymphocyte status was not associated with clinical activity. However, increase in tumor infiltrating lymphocyte density in tumor biopsy samples collected after the second dose of ipilimumab was associated with significantly greater clinical activity with ipilimumab compared to samples without increase in lymphocyte density. For a better understanding of the mechanisms of resistance to nivolumab in HNSCC, the investigators propose to study a cohort of longitudinal HNSCC samples from recurrent/metastatic HNSCC patients treated with nivolumab and identify biomarkers of response and resistance. The investigators will specifically focus on modulation of immune phenotype (ImmR) following two cycles of nivolumab as surrogate biomarker for response to nivolumab.

The primary endpoint will be the change in the percentage of immune cells that is caused by nivolumab treatment. Secondary endpoint will be safety of performing a biopsy after second nivolumab dose. Translational correlates will be tested in tumour tissue, plasma and germline DNA.

Investigator assessment of best overall response (BOR), determined between the date of first dose and the last tumor assessment (TA), will be image-based and scored using the RECIST 1.1. criteria. BOR will be defined as categorical variable with 3 levels { Benefit (complete response (CR), partial response (PR), stable disease (SD) lasting 6 months from the first nivolumab dose), no benefit (PD, progressive disease or SD lasting less than 6 months from the first nivolumab dose), and unknown} Longitudinal tissue biopsies will be collected from HNSCC patients treated with nivolumab . Biopsies will be taken at baseline, 24-72 hours after the second cycle of nivolumab and at progression.

Layout table for study information
Study Type : Observational
Estimated Enrollment : 50 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Predictive Biomarkers For Response To Nivolumab In Head and Neck Squamous Cell Carcinoma
Actual Study Start Date : May 1, 2018
Estimated Primary Completion Date : May 1, 2020
Estimated Study Completion Date : May 1, 2020

Resource links provided by the National Library of Medicine

Drug Information available for: Nivolumab

Group/Cohort Intervention/treatment
Recurrent/metastatic HNSCC

The investigators will include recurrent/metastatic HNSCC patients who progressed after cisplatin-based chemotherapy and are to be treated with nivolumab. Tumor biopsies will be performed at baseline, after the second cycle and at progression with appropriate written informed consent and the samples will be analyzed. Biomarker research will be performed.

The patients will receive intravenously nivolumab at dose of 240 mg every 2 weeks (240mg q2w). The patients will undergo tumor biopsy at baseline and within 24-72h after the second administration of treatment, and at progression of their disease.

Other: Biomarker Research
The investigators will include recurrent/metastatic HNSCC patients who progressed after cisplatin-based chemotherapy and are to be treated with nivolumab 240mg IV q 2 weeks. Patient samples will be collected with appropriate written informed consent and analyzed.

Drug: Nivolumab
The investigators will include recurrent/metastatic HNSCC patients who progressed after cisplatin-based chemotherapy and are to be treated with nivolumab 240mg IV q 2 weeks.
Other Name: Opdivo




Primary Outcome Measures :
  1. Change in the percentage of immune cells in post treatment compared to baseline biopsies [ Time Frame: 2 weeks ]
    Primary endpoint will be the change in mean percentage of immune cells that is caused by the nivolumab treatment


Secondary Outcome Measures :
  1. Safety of performing a biopsy after second nivolumab dose [ Time Frame: 6 weeks ]
    Incidence of adverse events attributable to nivolumab treatment

  2. Best overall response rate (BOR) according to RECIST 1.1 criteria [ Time Frame: One year ]
    BOR will be defined as categorical variable with 3 levels { Benefit (complete response (CR), partial response (PR), stable disease (SD) lasting 6 months from the first nivolumab dose), no benefit (PD, progressive disease or SD lasting less than 6 months from the first nivolumab dose), and unknown}

  3. Number of participants with tolerability to the treatment. [ Time Frame: From the 1st day of therapy and every week for 4 weeks maximum and 30 days after last therapy administration ] ]
    NCI common toxicity criteria will be used

  4. The burden of somatic non-synonymous mutations in association with BOR and survival [ Time Frame: At baseline ]
    Targeted gene sequencing using next generation sequencing will be performed

  5. The interferon-gamma gene signature in association with BOR and survival [ Time Frame: At baseline ]
    Nanostring gene expression profiling, multiple tumor, inflammatory- and immune related genes will be analyzed by multiplex Nanostring technology by using the nCounter PanCancer Immune Profiling 770-plex gene expression Panel

  6. The expression of PD-L1 in association with BOR and survival [ Time Frame: At baseline and at 4 weeks ]
    PD-L1 will be assessed in tumor cells and immune cells by immunohistochemistry

  7. The expression of human leukocyte antigens, HLA class I and HLA class II molecules in association with BOR and survival [ Time Frame: At baseline ]
    It will be assessed at RNA and protein level

  8. The presence of adaptive immunity cell populations [ Time Frame: At baseline and at 4 weeks ]
    The assessment will be performed using multiplex imaging

  9. The expression of PD-L2 in association with BOR and survival [ Time Frame: At baseline and at 4 weeks ]
    PD-L2 will be assessed in tumor cells and immune cells by immunohistochemistry

  10. PD-L1 expression in circulating tumor cells (CTCs) in association with BOR and survival [ Time Frame: At baseline and at 4 weeks ]
    The assessment will be performed with Parsotrix system


Biospecimen Retention:   Samples With DNA
Longitudinal tissue biopsies will be collected from HNSCC patients treated with nivolumab Biopsies will be taken at baseline, 24-72 hours after the second cycle of nivolumab and at progression.


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
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
The investigators will include recurrent/metastatic HNSCC patients who progressed after cisplatin-based chemotherapy and are to be treated with nivolumab.
Criteria

Inclusion Criteria:

  • Signed written informed consent before any trial-related procedure is undertaken
  • Male or female subjects aged ≥18 years
  • Availability of a formalin-fixed, paraffin-embedded tissue sample (FFPE) containing tumor

Exclusion Criteria:

  • no inform consent provided

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): NCT03652142


Contacts
Layout table for location contacts
Contact: AMANDA PSYRRI, MD +302105831664 psyrri237@yahoo.com
Contact: ELENI PAPASTAMATIOU +302105831256 lenagpa@yahoo.com

Locations
Layout table for location information
Greece
Attikon Hospital Recruiting
Athens, Chaidari, Greece
Contact: AMANDA PSYRRI, MD    +2105831664    psyrri237@yahool.com   
Sponsors and Collaborators
Attikon Hospital
Investigators
Layout table for investigator information
Principal Investigator: AMANDA PSYRRI, MD ATTIKON HOSPITAL, NATIONAL AND KAPODISTRIAN UNIVERSITY OF ATHENS, GREECE
  Study Documents (Full-Text)

Documents provided by AMANDA PSYRRI, Attikon Hospital:

Publications:
Layout table for additonal information
Responsible Party: AMANDA PSYRRI, Medical Oncologist, Associate Professor, National Kapodistrian University of Athens, Attikon Hospital
ClinicalTrials.gov Identifier: NCT03652142    
Other Study ID Numbers: CA209-8EN
First Posted: August 29, 2018    Key Record Dates
Last Update Posted: August 29, 2018
Last Verified: August 2018

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by AMANDA PSYRRI, Attikon Hospital:
HNSCC
DDR
DNA damage
DNA damage repair
PD-L1
PD-1
NIVOLUMAB
Head and Neck cancer
Additional relevant MeSH terms:
Layout table for MeSH terms
Carcinoma, Squamous Cell
Squamous Cell Carcinoma of Head and Neck
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Squamous Cell
Head and Neck Neoplasms
Neoplasms by Site
Cisplatin
Nivolumab
Antineoplastic Agents
Antineoplastic Agents, Immunological