Clinical Relevance of ROS (V-ros UR2 Sarcoma Virus Oncogene Homolog) Aberrations in Solid Tumours

This study is currently recruiting participants. (see Contacts and Locations)
Verified December 2013 by National University Hospital, Singapore
Sponsor:
Information provided by (Responsible Party):
National University Hospital, Singapore
ClinicalTrials.gov Identifier:
NCT01596374
First received: April 2, 2012
Last updated: December 10, 2013
Last verified: December 2013
  Purpose

Alterations involving the ROS (v-ros UR2 sarcoma virus oncogene homolog 1) gene such as mutations, overexpression and gene rearrangements has been implicated in carcinogenesis and has been demonstrated to be a relevant target for ALK inhibitors. While emerging reports have demonstrated the role of ROS rearrangement in non-small cell lung cancer and cholangiocarcinoma, the functional significance of ROS dysregulation in solid tumors remain largely unstudied. The investigators aims are: (1) To characterize the frequency of ROS gene fusion, ROS protein overexpression and ROS gene mutations in cell lines and tumors from patients with hepatocellular carcinoma, colorectal, gastric, breast, ovarian, cholangiocarcinoma and non-small cell lung cancer, (2) To identify novel ROS gene variants in human solid tumors harboring ROS aberrations using next generation sequencing (NGS), (3) To determine the functional relevance of novel ROS gene variants identified with NGS, (4) To characterize the sensitivity of cells with functionally relevant ROS aberrations using ROS tyrosine kinase inhibitors. ROS fusions and protein overexpression will be screened in a panel of cell lines and primary tumors using Fluorescence In-situ Hybridization and immunohistochemistry respectively. Targeted next-generation sequencing will be applied to identify ROS variants in matching cancer types demonstrating high levels of gene fusion and protein overexpression. Functional characterization of novel ROS variants will be performed by silencing (shRNA) and overexpressing candidate cell lines with the respective ROS mutations/fusions, and evaluating their effects on biological functions including cell proliferation, migration, invasion and apoptosis, as well as sensitivity against ROS/ALK inhibitors. The investigators anticipate findings from this study will improve the investigators understanding of aberrant ROS signaling in an expanded group of cancer types, and potentially identifying a larger group of cancer patients that will benefit from ROS targeted therapy.

Further insight of the role of ROS receptor tyrosine kinase will confirm it as a therapeutic target in human solid tumors and hence expand the indication of crizotinib and other dual ALK/ ROS inhibitors. Furthermore, given the rarity of ROS fusion receptor tyrosine kinase in reported cancers, defining the epidemiology of ROS aberrations in other unreported cancers harboring ROS pathway activation is essential to properly design future clinical trials of ROS inhibitors. The validation of ROS receptor tyrosine kinase will also provide a new therapeutic target in the treatment of cancer and expand the role of novel targeted agents. Findings from this study will further the investigators knowledge on the oncogenic functions of the ROS and the application of ROS inhibitors in an extended group of solid tumors.


Condition
Cancer

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Retrospective

Resource links provided by NLM:


Further study details as provided by National University Hospital, Singapore:

Primary Outcome Measures:
  • Characterize the frequency of ROS gene fusion, ROS protein overexpression and ROS gene mutations in cell lines and tumors
    To characterize the frequency of ROS gene fusion, ROS protein overexpression and ROS gene mutations in cell lines and tumors from patients with hepatocellular carcinoma, colorectal, gastric, breast, ovarian, cholangiocarcinoma and non-small cell lung cancer


Secondary Outcome Measures:
  • Identify novel ROS gene variants in human solid tumors harboring ROS aberrations using next generation sequencing (NGS)
  • Determine the functional relevance of novel ROS gene variants identified with NGS
  • Characterize the sensitivity of cells with functionally relevant ROS aberrations using ROS tyrosine kinase inhibitors

Estimated Enrollment: 2000
Study Start Date: August 2011
Estimated Primary Completion Date: July 2014 (Final data collection date for primary outcome measure)
  Eligibility

Ages Eligible for Study:   21 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population

Department of Pathology, NUH Tissue Repository, The samples collected for the study are leftover clinical samples and the patients have consented for their samples to be used for research.

Criteria

Inclusion Criteria:

- Patients with cancer

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01596374

Contacts
Contact: Ross Soo, MBBS +65 6779 5555 Ross_Soo@nuhs.edu.sg

Locations
Singapore
Nationa University Hospital Recruiting
Singapore, Singapore
Contact: Ross Soo, MBBS    +65 6779 5555    Ross_Soo@nuhs.edu.sg   
Principal Investigator: Ross Soo, MBBS         
Sponsors and Collaborators
National University Hospital, Singapore
  More Information

No publications provided

Responsible Party: National University Hospital, Singapore
ClinicalTrials.gov Identifier: NCT01596374     History of Changes
Other Study ID Numbers: 2011/01714
Study First Received: April 2, 2012
Last Updated: December 10, 2013
Health Authority: Singapore: Domain Specific Review Boards

ClinicalTrials.gov processed this record on October 30, 2014