Clinical trial NCT05382585: Newer Therapeutic Targets in Head and Neck Cancers
Official title: A Cohort Study to Identify Newer Therapeutic Targets in Head and Neck Cancers
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Head Neck Cancer
Oral Cancer
Keywords: Next generation sequencing
predictive biomarker
Lead sponsor: Banaras Hindu University
Sponsor class: OTHER
First posted: 2022-05-19
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Histologically proven cases of Head and neck cancer undergoing treatment will be included, Next generation sequencing will be done and cohort will be followed up for 10 years

Brief summary: Based on the recently identified mutations in HNSCCs, the major pathologic pathways implicated in the tumorigenesis of HNSCC include dysregulation of four processes:

1. cellular survival and proliferation (e.g., TP53, EGFR, MET, and PIK3CA);
2. cell-cycle control (e.g., CDKN2A and CCND1);
3. cellular differentiation (e.g., NOTCH1); and
4. Adhesion and invasion signaling (e.g., FAT1).7 TP53, EGFR, PIK3CA, CDKN2A, CCND1, and MET participate in several common signaling pathways.

Alterations of these genes are most frequently seen in alcohol and tobacco-related HNSCC. However their role in prognostication and selection of therapeutics is not known

Detailed description: Sample size:

Patients with squamous cell carcinoma of oral cavity fulfilling the inclusion and exclusion criteria and willing to participate will be included in this study.

Method:

Comprehensive history and physical examination of the patients will be carried out and all the details will be recorded in the preset proforma. All routine investigations as indicated including a biopsy to establish a diagnosis and CT of the head and neck to measure the tumor dimensions and stage the disease before initiation of treatment will be recorded. The paraffin embedded tissue will be studied for expression of various genetic mutations using NGS platform. Brush cytology will be collected in liquid medium for HPV typing using PCR.

The Ion AmpliSeq™ Cancer Hotspot Panel v3 will be used to detect hotspot regions of 161 oncogenes and tumor suppressor genes This research panel, with improved primer design, contains 4,648 total 4 pools (DNA pool 1: 1,891 amplicons. DNA pool 2: 1,890 amplicons. RNA pool 1: 447 amplicons. RNA pool 2: 420 amplicons.), enabling researchers to sequence challenging samples of formalin-fixed, paraffin-embedded (FFPE) tissue. Copy Number Variants (CNVs), Gene Fusions, Insertions-Deletions (indels), Single Nucleotide Polymorphisms (SNPs), Somatic Variants are identified.

HPV DNA PCR METHODOLOGY

DNA will be isolated by using QIAamp DNA mini kit (Qiagen, Hilden, Germany). The presence of HPV will be detected by using the digene® HC2 HPV DNA Test- The digene HC2 HPV DNA Test uses Hybrid Capture 2 technology to detect high-risk and low-risk HPV genotypes. It uses in vitro microplate assay based on signal-amplified nucleic acid hybridization that uses chemiluminescence for the qualitative detection of 18 types of human papillomavirus (HPV) (13 high risk and 5 low risk) DNA in cervical specimens. The test uses an RNA probe cocktail that detects 13 high-risk HPV types (16/18/31/33/35/39/45/51/52/56/58/59/68) and 5 low-risk types (6/11/42/43/44).

Eligibility criteria: Inclusion Criteria:

* Histologically proven cases of primary head and neck cancers.

Exclusion Criteria:

* Patients under 18 years of age
* Pregnant and lactating women
* Multiple cancers or patients with cancer of other sites.

Primary outcomes:
measure: Over all survival
timeFrame: 10 years
measure: Relapse free survival
timeFrame: 10 years
Secondary outcomes:
measure: Progression free survival
timeFrame: 5 years
Other outcomes:
Locations:
city: Varanasi
country: India
facility: Banaras Hindu University
state: UP
Study officials:
affiliation: Professor
name: Manoj Pandey, MS, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Batta N, Pandey M. Mutational spectrum of tobacco associated oral squamous carcinoma and its therapeutic significance. World J Surg Oncol. 2019 Nov 27;17(1):198. doi: 10.1186/s12957-019-1741-2.