Comprehensive Genomic Profiling of Recurrent / Metastatic Oral Cancer for Personalized Treatment: A Novel Approach to Improve Clinical Outcomes and Affordability
Trial Snapshot
- Phase
- Not Applicable
- Status
- Not yet recruiting
- Sponsor
- ICMR
- Enrollment
- 248
- Locations
- 2
- Primary Endpoint
- 1. Identification of response / resistance markers in TMC-I treated oral cancer patients using WES and RNA-sequencing and their correlation with treatment outcomes.
Study Overview
Brief Summary
Rationale/ gaps in existing knowledge:
Oral cancer (OC), a major health concern globally, particularly in India, is often diagnosed at advanced stages. Despite understanding its epidemiology and pathogenesis, survival rates remain dismal and effective molecular biomarkers are unintelligible, limiting accessible and tolerable treatment options, especially in Low Middle Income Countries. Tata Memorial Hospital has developed an affordable and effective regimen combining low-dose immunotherapy with metronomic chemotherapy (TMC-I), with improved overall survival. Understanding genomic profile of Indian oral cancer patients is crucial for identifying novel biomarkers predictive of treatment response and prognosis.
Novelty: This study proposes to use comprehensive genomic profiling, specifically targeted exome, Whole Exome Sequencing (WES) and RNA-seq to predict treatment responses in oral cancer patients for personalized treatments and selecting appropriate patients for TMC-I, while sparing toxicities in non-responders.
Objectives: To identify genetic alterations in Indian oral cancer patients receiving TMC-I, correlate these alterations with treatment outcomes, validate them on a larger patient cohort, and longitudinally monitor them over time using liquid biopsy (ctDNA) approach to understand disease biology and resistance mechanisms.
Methods: WES and RNA-sequencing will be performed on baseline tumour samples from TMC-I-treated patients. Genetic profiles so obtained will be correlated with clinical outcomes to identify response and resistance markers. Targeted sequencing on baseline tumour and blood samples from treatment-naive patients will validate these findings. Longitudinal monitoring using liquid biopsy will track genetic changes during treatment.
Expected outcome: This study aims to develop a tool for personalized oral cancer treatment, selecting patients for low-dose immunotherapy and chemotherapy based on individual responses. This approach may enhance survival, quality of life, overall health, and improve clinical outcomes in patients with oral cancer in India and globally.
Study Design
- Study Type
- Observational
Eligibility Criteria
- Ages
- 18.00 Year(s) to 99.00 Year(s) (—)
- Sex
- All
Inclusion Criteria
- •Patients must have recurrent or metastatic oral cancer at the time of diagnosis and must not have undergone any prior treatment.
- •Ability to follow study procedures, including regular follow-ups and assessments, with signed informed consent.
Exclusion Criteria
- •Patients who have already received palliative systemic chemotherapy for oral cancer will be excluded.
- •Severe allergies to drugs in the TMC-I regimen.
- •Significant cardiovascular issues like stroke, heart attack, or serious arrhythmias requiring medication.
Outcomes
Primary Outcomes
1. Identification of response / resistance markers in TMC-I treated oral cancer patients using WES and RNA-sequencing and their correlation with treatment outcomes.
Time Frame: For objective 1, 50 patient samples will be collected retrospectively for 6 months followed by data analysis and gene panel development. | For objective 2, 198 patient samples will be collected prospectively for 1.5 years (6th to 18th month of the study), followed by data analysis and interpretation.
2. Validation of identified genomic alterations on a larger cohort of patient samples to confirm the results.
Time Frame: For objective 1, 50 patient samples will be collected retrospectively for 6 months followed by data analysis and gene panel development. | For objective 2, 198 patient samples will be collected prospectively for 1.5 years (6th to 18th month of the study), followed by data analysis and interpretation.
Secondary Outcomes
- Understanding disease biology and resistance mechanisms by longitudinal monitoring of the identified alterations over time using liquid biopsy (ctDNA) approach.(For this objective, 50 patients from the earlier 198 patients will be selected prospectively and their samples collected every 3-4 months for 1.5 to 2 years, for sequencing using ctDNA approach, followed by data analysis and interpretation.)
Investigators
Dr Vanita Noronha
Tata Memorial Hospital