Afatinib and Nivolumab as Treatment for Recurrent/Metastatic Squamous Cell Carcinoma of the Head and Neck
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|ClinicalTrials.gov Identifier: NCT03652233|
Recruitment Status : Withdrawn (Low accrual)
First Posted : August 29, 2018
Last Update Posted : June 20, 2019
|Condition or disease||Intervention/treatment||Phase|
|Recurrent Squamous Cell Carcinoma of the Head or Neck Metastatic Squamous Cell Carcinoma of the Head or Neck Squamous Cell Carcinoma||Drug: Nivolumab Drug: Afatinib||Phase 1|
Phase I: To determine dose limiting toxicities (DLTs) and maximum tolerated dose (MTD) of afatinib when given in combination with nivolumab for subjects with recurrent/metastatic Squamous Cell Carcinoma of the Head and Neck not previously treated with immunotherapy
Phase IB: To determine long term safety of afatinib in combination with nivolumab when administered to subjects with recurrent/metastatic Squamous Cell Carcinoma of the Head and Neck who had experienced disease progression during or after platinum- and cetuximab-based chemotherapy regimen.
To assess progression free survival and overall survival of afatinib in combination with nivolumab when given to subjects with recurrent/metastatic Squamous Cell Carcinoma of the Head and Neck not previously treated with immunotherapy.
To estimate HPV stratified ORR as assessed by irRECIST in recurrent/metastatic Squamous Cell Carcinoma of the Head and Neck not previously treated with immunotherapy.
- Determination of key molecular alterations that may confer treatment resistance. Specifically, we will examine key somatic mutations in ERBB1 (exons 18-21), ERBB2 (exon 20), and BRAF (V600) genes. We will further characterize the expression levels of ErbB2 and phosphatase and tensin homolog (PTEN) in tumor samples.
- Characterization of active CD8+ T-cell density and PD-L1 expression levels in the tumor parenchyma pre- and on-treatment. Immunogenicity will be assessed by expression and localization of key molecules PD-1, PD-L1, CTLA-4, TIM-3, LAG-3 and OX40 within the tumor parenchyma.
- Characterization of circulating monocytic myeloid-derived suppressor cells (m-MDSCs) frequency from pre-treatment peripheral blood samples.
- Characterization of HBD3 expression in the tumor parenchyma from pre-treatment tumor tissue samples.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||0 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Afatinib and Nivolumab for Treatment of Recurrent/Metastatic Squamous Cell Carcinoma of the Head and Neck (SCCHN) Not Previously Treated With Immunotherapy.|
|Actual Study Start Date :||November 2, 2018|
|Estimated Primary Completion Date :||November 2021|
|Estimated Study Completion Date :||November 2022|
|Experimental: Afatinib and Nivolumab||
Given by vein every 14 days for up to 12 months
Taken by mouth daily for up to 12 months
- Maximum tolerated dose (phase I) [ Time Frame: Up to 42 days ]
- Dose limiting toxicities (phase I) [ Time Frame: Up to 42 days ]
- Number of participants with treatment-related adverse events as assessed by CTCAE version 4.0 [ Time Frame: Up to 24 months ]
- Progression free survival [ Time Frame: From date of enrollment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 3 years ]
- Overall survival [ Time Frame: From date of enrollment to date of death from any cause assessed up to 3 years. ]
- Objective response rate [ Time Frame: Up to 24 months ]
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): NCT03652233
|Principal Investigator:||Mike Gibson, MD, PhD||Vanderbilt-Ingram Cancer Center|