Identifying Omics-based biomarkers for immunotherapy response in Indian oral cancer: A prospective study.
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 发起方
- 入组人数
- 100
- 试验地点
- 2
- 主要终点
- 1. To identify the molecular genomic alterations in Indian immuno+chemotherapy-treated OSCC patients .
研究概览
简要总结
Oral squamous cell carcinoma (OSCC) is a prevalent and aggressive form of cancer in India, posing a significant public health challenge. While conventional treatments like chemotherapy and radiotherapy are utilized, their efficacy is often limited, resulting in poor survival rates. Immunotherapy, a promising alternative, leverages the body’s own immune system to combat cancer by reversing T-cell inactivation and immunosuppression through the blockade of immune check point molecules. This approach has shown encouraging results in various cancers, offering a potential lifeline for OSCC patients. However, a significant hurdle remains: approximately half of all patients do not respond to immunotherapy. This variability in response is attributed to complex genomic factors, including tumor mutation burden, germline Human Leukocyte Antigen profiles, neoantigen burden, and T-cell receptor repertoire diversity. Unfortunately, the specific landscape of these molecular alterations in Indian OSCC patients, particularly in the context of immunotherapy response, remains largely uncharacterized. This lack of knowledge hinders clinicians’ ability to effectively stratify patients and tailor treatment strategies.
To address this gap, a study is proposed to investigate the genomic and transcriptomic profiles of Indian OSCC patients undergoing immunotherapy in conjunction with chemotherapy. The primary objective is to identify molecular markers that differentiate responders from non-responders. By employing high-throughput exome sequencing, whole transcriptome sequencing, and T-cell receptor repertoire sequencing on samples from 100 patients recruited from Tata Memorial Hospital, Mumbai, researchers aim to comprehensively characterize the genomic alterations associated with immunotherapy response. This analysis will include the identification of somatic mutations, mutational signatures, copy-number alterations, copy number signatures, germline HLA alteration profiles, tumor neo antigenic diversity, and T-cell receptor repertoire diversity. Furthermore, the study will characterize the immune-cell in filtration dysregulation in responders and non-responders. The ultimate goal is to develop an integrative scoring system that combines multi-omics immunogenic data to accurately predict patient response to immunotherapy. This research has the potential to significantly improve patient outcomes by enabling personalized treatment strategies, avoiding ineffective therapies, and reducing the financial burden associated with immunotherapy. The study will provide critical insights into the molecular mechanisms underlying immunotherapy response in Indian OSCC patients, paving the way for more effective and targeted cancer care.
研究设计
- 研究类型
- Observational
入排标准
- 年龄范围
- 18.00 Year(s) 至 85.00 Year(s)（—）
- 性别
- All
入选标准
- •Subjects must have T3 N1-N3 or T4 HNSCC of the oral cavity who has received immunotherapy in either the palliative or adjuvant treatment setting.
- •Age: Male or female or transgender subjects aged more than or equal to 18 years.
- •Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-
- •Subjects must have normal organ and marrow function as per institute protocols
- •Patients with HIV will be potentially eligible, as long as they have a CD4 count less than 200, are on concurrent HAART (highly active antiretroviral therapy), and have absence of active AIDS defining conditions.
- •Both men and women of all races and ethnic groups will be eligible for this study.
- •Willing and able to comply with all study requirements, including treatment, able to be followed up at regular intervals and/or nature of required assessments.
- •Ability to understand and the willingness to sign a written informed consent document.
排除标准
- •Subjects who are receiving any other investigational agents.
- •Within 2 weeks of administration of a chemotherapeutic agent.
- •Current use of immunosuppressive medication, EXCEPT for the following: a.
- •intranasal, inhaled, topical steroids, or local steroid injection (e.g., intra-articular injection); b.
- •Systemic corticosteroids at physiologic doses less than or equal to 10 mg per day of prednisone or equivalent; c.
- •Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication) d.
- •Steroids for raised intracranial pressure due to the disease itself e,Steroid use for avoidance or treatment of emesis
- •Uncontrolled comorbidities including active autoimmune disease that might deteriorate when receiving a chemotherapeutic agent.
- •Clinically significant (i.e., active) cardiovascular disease: cerebrovascular accident/stroke (less than 6 months prior to enrollment), myocardial infarction (less than 6 months prior to enrollment), unstable angina, congestive heart failure (more than or equal to New York Heart Association Classification Class II), or serious cardiac arrhythmia requiring medication.
- •Patients with severe renal and liver dysfunction Child Pugh B or C.
- •Prior organ transplantation including allogeneic stem-cell transplantation.
- •Known prior severe hypersensitivity to investigational product or any component in its formulations, including known severe hypersensitivity reactions to monoclonal antibodies (NCI-CTCAE v5.0 Grade more than or equal to 3).
- •Pregnant and lactating women will be excluded from this study.
结局指标
主要结局
1. To identify the molecular genomic alterations in Indian immuno+chemotherapy-treated OSCC patients .
时间窗: 1.at baseline | 2.At 8 weeks, at end of treatment, and during follow-up (up to 12 months). | 3.At baseline, 8 weeks, and at follow-up (12 months). | 4.At baseline, 2–4 months, and at follow-up (12 months). | 5. At each clinical visit during treatment and follow-up.
2. To identify the molecular marker alteration profile differentiating the immunotherapy-responder and non-responders.
时间窗: 1.at baseline | 2.At 8 weeks, at end of treatment, and during follow-up (up to 12 months). | 3.At baseline, 8 weeks, and at follow-up (12 months). | 4.At baseline, 2–4 months, and at follow-up (12 months). | 5. At each clinical visit during treatment and follow-up.
3.To characterize the immune-cell infiltration dysregulation in the responder and non-responders in response to chemo+immunotherapy
时间窗: 1.at baseline | 2.At 8 weeks, at end of treatment, and during follow-up (up to 12 months). | 3.At baseline, 8 weeks, and at follow-up (12 months). | 4.At baseline, 2–4 months, and at follow-up (12 months). | 5. At each clinical visit during treatment and follow-up.
4.To assess quality of life in patients receiving immunotherapy.
时间窗: 1.at baseline | 2.At 8 weeks, at end of treatment, and during follow-up (up to 12 months). | 3.At baseline, 8 weeks, and at follow-up (12 months). | 4.At baseline, 2–4 months, and at follow-up (12 months). | 5. At each clinical visit during treatment and follow-up.
5.To assess adverse events as per Common Terminology Criteria for Adverse event
时间窗: 1.at baseline | 2.At 8 weeks, at end of treatment, and during follow-up (up to 12 months). | 3.At baseline, 8 weeks, and at follow-up (12 months). | 4.At baseline, 2–4 months, and at follow-up (12 months). | 5. At each clinical visit during treatment and follow-up.
次要结局
未报告次要终点
研究者
Dr Kumar Prabhash
Tata Memorial Centre