CTRI/2024/07/071572 [Registered on: 30/07/2024] Trial Registered Prospectively
Last Modified On:
25/07/2024
Post Graduate Thesis
No
Type of Trial
Observational
Type of Study
Cohort Study
Study Design
Other
Public Title of Study
Liquid biopsy in metastatic brain tumours
Scientific Title of Study
Paired exosomal mRNA, tumoral somatic DNA sequencing and DNA methylation profiling in patients with primary and / or metastatic brain tumors on radiology, to develop a liquid biopsy test.
Trial Acronym
NIL
Secondary IDs if Any
Secondary ID
Identifier
NIL
NIL
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Name
Dr Amitava Ray MBBS MD FRCSEd FRCS Neurosurgery
Designation
Founder, Director and Clinical Lead
Affiliation
EXSEGEN GENOMICS RESEARCH PRIVATE LIMITED
Address
Room Number 2 Third Floor, 8-2-293/82/A/240, Road No. 36 Jubilee Hills, Hyderabad.
Hyderabad TELANGANA 500033 India
Phone
9000420030
Fax
Email
amit@exsegen.com
Details of Contact Person Scientific Query
Name
Dr Amitava Ray MBBS MD FRCSEd FRCS Neurosurgery
Designation
Founder, Director and Clinical Lead
Affiliation
EXSEGEN GENOMICS RESEARCH PRIVATE LIMITED
Address
Room Number 2 Third Floor, 8-2-293/82/A/240, Road No. 36 Jubilee Hills, Hyderabad.
TELANGANA 500033 India
Phone
9000420030
Fax
Email
amit@exsegen.com
Details of Contact Person Public Query
Name
Dr Amitava Ray MBBS MD FRCSEd FRCS Neurosurgery
Designation
Founder, Director and Clinical Lead
Affiliation
EXSEGEN GENOMICS RESEARCH PRIVATE LIMITED
Address
Room Number 2 Third Floor, 8-2-293/82/A/240, Road No. 36 Jubilee Hills, Hyderabad.
TELANGANA 500033 India
Phone
9000420030
Fax
Email
amit@exsegen.com
Source of Monetary or Material Support
Exsegen Genomics Research Pvt Ltd, Third Floor, 8-2-293/82/A/240, Road No. 36, Jubilee Hills,
Hyderabad, Telangana, India 500033.
Primary Sponsor
Name
Exsegen Genomics Research Pvt Ltd
Address
Third Floor, 8-2-293/82/A/240, Road No. 36, Jubilee Hills,
Hyderabad, Telangana, 500033
Type of Sponsor
Research institution
Details of Secondary Sponsor
Name
Address
NIL
NIL
Countries of Recruitment
India
Sites of Study
No of Sites = 1
Name of Principal
Investigator
Name of Site
Site Address
Phone/Fax/Email
Dr I Vijay Sundar
Cancer Institute (WIA)
Room no 3, Department of Neurosurgery,38, Sardar Patel Road Adyar, Chennai Chennai TAMIL NADU
9566221211
drvijaysundar@gmail.com
Details of Ethics Committee
No of Ethics Committees= 1
Name of Committee
Approval Status
Institutional Ethics Committee, Cancer Institute (WIA)
Approved
Regulatory Clearance Status from DCGI
Status
Not Applicable
Health Condition / Problems Studied
Health Type
Condition
Patients
(1) ICD-10 Condition: C00-D49||Neoplasms,
Intervention / Comparator Agent
Type
Name
Details
Comparator Agent
Nil
Nil
Inclusion Criteria
Age From
1.00 Day(s)
Age To
80.00 Year(s)
Gender
Both
Details
1. Subjects with suspected primary or secondary brain tumor on neuroimaging
2. Age-any age with proper consent/assent
3. Provision of signed and dated informed consent form; by patient or guardian/parent
4. Stated willingness to comply with all study procedures
ExclusionCriteria
Details
Patients who fail to meet all of the above criteria for cases will be excluded.
Method of Generating Random Sequence
Not Applicable
Method of Concealment
Not Applicable
Blinding/Masking
Outcome Assessor Blinded
Primary Outcome
Outcome
TimePoints
Ability to distinguish between a secondary malignant neoplasm and a non-malignant condition using a liquid biopsy test, with an accuracy approaching the traditional biopsy.
Baseline, 12 weeks, 26 weeks and 52 weeks
Secondary Outcome
Outcome
TimePoints
1. Ability to distinguish between the secondary neoplasm & other primary malignant neoplasms of the brain.
2. Ability to diagnose the possible site of the primary neoplasm from which the secondary malignant brain neoplasm has arisen.
Baseline, 12 weeks, 26 weeks & 52 weeks
Target Sample Size
Total Sample Size="1000" Sample Size from India="1000" Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials" Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials"
Phase of Trial
N/A
Date of First Enrollment (India)
08/08/2024
Date of Study Completion (India)
Applicable only for Completed/Terminated trials
Date of First Enrollment (Global)
Date Missing
Date of Study Completion (Global)
Applicable only for Completed/Terminated trials
Estimated Duration of Trial
Years="1" Months="0" Days="0"
Recruitment Status of Trial (Global)
Not Applicable
Recruitment Status of Trial (India)
Not Yet Recruiting
Publication Details
N/A
Individual Participant Data (IPD) Sharing Statement
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
Brief Summary
One of the hallmarks of cancer biology, and indeed, its most dreaded complication, is metastasis to distant sites via the lymphatic and hematogenous systems [1]. In 2018, an estimated 632,405 patients in the United States were living with metastatic disease arising mainly from the six most common cancer types (breast, prostate, lung, colorectal, bladder and melanoma) [2]. Traditionally, over 90% of cancer deaths have been attributed to metastatic cancer, and a population-based cancer registry in Norway identified metastatic disease as a contributory factor in two-thirds of deaths in patients with solid tumors [3].
Brain metastases (BM) are the most common central nervous system tumor, occurring nearly 10 times as frequently as primary CNS malignancies [4] and peaks in incidence between the ages of 65 to 80 years. 2 percent of all cancer patients and 12.1 percent of patients with metastatic disease at the time of diagnosis have detectable BM [5]. Some patients may be asymptomatic at the time of diagnosis andBMs are detected following screening, but up to 75% may present with neurological symptoms including seizures, focal deficits, altered sensorium, headaches, nausea or vomiting and somnolence [6-7]]. Symptomatic BM may be the presenting feature of metastatic cancer in up to 19% of patients [14]. The Graded Prognostic Assessment (GPA) score is used to estimate survival in patients diagnosed with BM [8]. Patients with BM require multidisciplinary input, with treatment options including surgical resection (metastatectomy), whole brain radiation therapy (WBRT) or stereotactic radiosurgery/radiotherapy (SRS and SRT), and systemic therapy has increasingly proven effective in certain subtypes of non-small cell lung cancer (NSCLC), breast cancer and melanoma[9]. Despite these advances, the presence of BM confers a median survival of 12 months or less across nearly all primary cancers [5].
The differentiation of primary and secondary malignant lesions of the brain is critical in the management of the patients. Currently, the only method of differentiating between primary and metastatic lesions is a biopsy, which itself comes with all its risks and pitfalls. In addition, a number of patients with a known malignancy develop a second lesion in the brain that is also a primary tumour. Even for these lesions there is no easy way of diagnosis[2].
The development of reliable liquid biopsies using blood or other body fluids for the diagnosis and evaluation of different cancers as an alternative to standard tissue biopsies is an area of active research [10]. Every tumor secretes within the blood (and sometimes other bodily fluids in contact with the tumor) endovesicles (small ‘bubbles’ that get detached from the cell carrying with it a representative sample of its cargo), cell-free DNA (DNA of dead cells released into the blood) and circulating tumor cells [11]. As the amount of extra cellular vesicles, circulating tumor DNA (ctDNA) and circulating tumor cells (CTCs) are usually directly proportional to the grade of tumor, the highest grade is better represented in the blood. Liquid biopsy tests have been approved by the USFDA as companion diagnostic tests for the targeted treatment of NSLC (Cobas EGFR mutation Test v2), breast cancer (therascreen PI3LA RGQ PCR Kit) and even pan-cancer testing covering ovarian cancer, prostate cancer in addition to NSCLC and breast cancer (Guardant 360 CDx and FoundationOne Liquid CDx) [12].
Exosomes or extracellular vesicles are increasingly implicated in cancer development and progression, with a growing interest in their potential as diagnostic and therapeutic biomarkers [13]. In a pilot study we conducted on gliomas, we have already established an ~80% sensitivity and specificity of the exosomal assay in testing for the cancer marker epidermal growth factor (EGFR) receptor [14]. By increasing the number of markers tested, it may be possible to improve the sensitivity and specificity of liquid biopsies using the exosomal platform to a degree that can obviate the need for a tissue biopsy. By characterizing the exosomal profiles of patients diagnosed with BM as well as the primary cancers responsible for the majority of BM, it also may be possible to develop a single blood test capable of distinguishing between primary CNS tumors and brain metastases and identifying the primary cancer.
Hypothesis: The exosomal platform provides an ideal stage to be able to screen, diagnose and prognosticate brain tumors for treatment decisions without the need for a tissue biopsy in both primary (CNS) and secondary (metastatic) tumors.
References:
1. Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011 Mar 4;144(5):646–74.
2. Gallicchio L, Devasia TP, Tonorezos E, Mollica MA, Mariotto A. Estimation of the Number of Individuals Living with Metastatic Cancer in the United States. JNCI: Journal of the National Cancer Institute. 2022 Nov 1;114(11):1476–83.
3. Dillekås H, Rogers MS, Straume O. Are 90% of deaths from cancer caused by metastases? Cancer Med. 2019 Aug 8;8(12):5574–6.
5. Cagney DN, Martin AM, Catalano PJ, Redig AJ, Lin NU, Lee EQ, et al. Incidence and prognosis of patients with brain metastases at diagnosis of systemic malignancy: a population-based study. Neuro Oncol. 2017 Oct;19(11):1511–21
6. Lamba N, Wen PY, Aizer AA. Epidemiology of brain metastases and leptomeningeal disease. Neuro Oncol. 2021 Sep 1;23(9):1447–56.
7. Füreder LM, Widhalm G, Gatterbauer B, Dieckmann K, Hainfellner JA, Bartsch R, et al. Brain metastases as first manifestation of advanced cancer: exploratory analysis of 459 patients at a tertiary care center. Clin Exp Metastasis. 2018 Dec 1;35(8):727–38.
8. Sperduto PW, Mesko S, Li J, Cagney D, Aizer A, Lin NU, et al. Survival in Patients with Brain Metastases: Summary Report on the Updated Diagnosis-Specific Graded Prognostic Assessment and Definition of the Eligibility Quotient. JCO. 2020 Nov 10;38(32):3773–84.
9. Aizer AA, Lamba N, Ahluwalia MS, Aldape K, Boire A, Brastianos PK, et al. Brain metastases: A Society for Neuro-Oncology (SNO) consensus review on current management and future directions. Neuro-Oncology. 2022 Oct 1;24(10):1613–46.
10. Scarlotta M, Simsek C, Kim AK. Liquid Biopsy in Solid Malignancy. Genet Test Mol Biomarkers. 2019 Apr;23(4):284–96.
12. Chen Z, Li C, Zhou Y, Yao Y, Liu J, Wu M, et al. Liquid biopsies for cancer: From bench to clinic. MedComm [Internet]. 2023 Aug [cited 2023 Nov 1];4(4).
13. Wang X, Tian L, Lu J, Ng IOL. Exosomes and cancer - Diagnostic and prognostic biomarkers and therapeutic vehicle. Oncogenesis. 2022 Sep 15;11(1):1–12.
14. Manda SV, Kataria Y, Tatireddy BR, Ramakrishnan B, Ratnam BG, Lath R, et al. Exosomes as a biomarker platform for detecting epidermal growth factor receptor-positive high-grade gliomas. J Neurosurg. 2018 Apr;128(4):1091–101.