Personalized Oncogenomics (POG) Program of British Columbia

Advanced Cancers Clinical Trial

Official title:

Personalized OncoGenomics (POG) Program of British Columbia: Connecting Cancer Genomics to Cancer Care

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02155621
• Other study ID #: POG 4.0
• Status: Recruiting
• Phase: N/A
• Start date: July 2014
• Est. completion date: December 2025

Study information

• Verified date: January 2021
• Source: British Columbia Cancer Agency
• Contact: Janessa J Laskin, MD
• Email: jlaskin[@]bccancer.bc.ca
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The genomic heterogeneity of cancers implies that to effectively use targeted therapies the investigators will need to assess each individual cancer and match it to a biologically relevant targeted therapy. The investigators will use full genome sequencing to try to identify cancer "drivers" and corresponding drugs that may inhibit these pathways.

Description:

Carcinogenesis is an immensely complex process such that even within a histologic cancer subtype - for example adenocarcinoma of the lung or breast - there is significant variability in cancer behaviour and response to therapy. Analyses of individual patients demonstrate unique molecular signatures for every cancer examined. Frequently, multiple different pathways are involved in disease growth and progression and the dominant process varies from person to person and perhaps even within different sites of disease within one person. As well these variations evolve in response to treatment.

Recognizing genetic aberrations that promote disease facilitates targeted treatment; this has been demonstrated in several small subgroups of cancers in which specific genetic mutations or translocations have been successfully treated with targeted chemotherapy agents. With many recognized mutations and aberrations, personalized evaluation of the genetic signature encoded in DNA and RNA may provide important diagnostic information and potentially enable directed therapy to the appropriate oncologic pathway thereby providing information to help guide chemotherapy choices

Our initial pilot project demonstrated the feasibility of this approach at our institution (with 100 patients). We now know it is possible to identify and consent patients, sequence the genome and transcriptome, analyze and report abnormalities, and identify potential actionable targets in a clinically relevant time frame.

The Personalized OncoGenomics (POG) program has been operational across the province of BC since 2012. The initial two-year phase established the infrastructure and workflow by which patients with metastatic or incurable cancers could be identified, consented, and biopsied for genomic sequencing in a clinically accredited lab (Laskin et al., 2015). The next phase of the POG program (2014 - 2017) included a strong educational and engagement process such that 83 (80%) of the medical oncologists at BC Cancer were trained to consent and enroll patients onto POG. This means that the oncology community in BC has a broad education in cancer genomics and how these data may be applied to individual patients. Since 2017, the program has been integrated into the Vancouver Cancer Centre's phase 1 clinical trials unit and the focus has shifted to use the study patients and data to address more focused clinical therapeutic trials such as the CCTG CAPTUR study (Skamene et al., 2018). POG-like WGTA has been the driving force behind the creation of the Terry Fox Marathon of Hope Cancer Centre Network (MOHCCN) which is a national program for cancer genomic data sharing across Canada.

The overarching theme of this POG Program is to create a comprehensive cataloguing of somatic cancer mutations and cellular pathway abnormalities that could generate profound insights into genetic patterns that underlie particular cancer phenotypes, and provide valuable prognostic and predictive information.

Eligible subjects will have several samples analyzed: a fresh tumour biopsy (typically 5 cores are required), a blood sample for normal comparison and archival tumours when available. Also, technology has improved such that we may consider using paraffin embedded materials. Comprehensive DNA and RNA sequencing is performed followed by an in-depth bioinformatic analysis to identify somatic mutations, gene expression changes or other abnormalities that might be cancer "drivers" or provide actionable (diagnostic) or druggable targets. The POG team meets every week to discuss the detailed genomic reports for patients, consider additional validation tests when necessary, and debate research questions. The clinicians (typically 5 - 10) come to a consensus on what systemic therapies might be appropriate based on these results. Whenever possible subjects are matched to clinical trials.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 5000
• Est. completion date: December 2025
• Est. primary completion date: December 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 85 Years

Eligibility

Inclusion criteria:

1. Patients must agree to allow their archival specimens to be used and possibly completely depleted for these analyses.

2. Willing and able to have a study-specific biopsy or resection of the tumour or metastatic site OR if there is adequate archival material available, either fresh frozen or FFPE (if specimen is thought to be adequate) that is taken after the most recent chemo or radiation. Ideally this sample should have been collected within 16 weeks of the date of consent. If archival tissue is not adequate and if a biopsy is not feasible or deemed medically safe by the investigators the patient would become ineligible.

3. Patients must understand and agree to provide a blood test (or other sample of normal DNA) for germline genomic analysis.

4. ECOG PS 0 or 1.

5. Age >/= 18 years.

6. Estimated life expectancy >/= 6 months and high likelihood of being clinically fit for a therapeutic clinical trial in 3-6 months.

7. Measurable disease with RECIST v1.1 (or updated version).

8. Adequate organ function.

9. Patients must clearly understand that this data may be used to help guide treatment recommendations, including the avoidance of some therapeutic agents or the suggestion to use standard cytotoxic chemotherapy agents.

10. Willingness to have their de-identified genomic and clinical data shared with national and international research collaborators and data sharing platforms (as detailed in the consent form).

11. Willingness to be contacted for future studies based on the data that is generated by participation in POG; included in this is the anticipation that patient would be fit or a candidate for clinical trials.

Exclusion criteria:

1. Unable or unwilling to consent to the above tissue and blood requirements.

2. Significant medical condition that in the opinion of the treating or consenting oncologist and/or the POG central office review team renders the subject not suitable for participation. This includes the likelihood that a subject would be suitable for a clinical trial within 12 weeks after POG biopsy.

3. Unwilling or unable to provide treatment and outcome follow up information to the BC Cancer or affiliated investigators.

4. Unwilling to receive medically actionable findings (germline and/or somatic).

Related Conditions & MeSH terms

• Advanced Cancers
• Cancers That Cannot be Treated With Curative Intent
• Metastatic Cancers
• Neoplasm Metastasis

Intervention

Genetic:
• Genome sequencing
Subjects will have their cancers biopsied and blood samples taken; both will undergo genomic sequencing and analysis

Locations

Country	Name	City	State
Canada	BC Cancer Agency	Vancouver	British Columbia

Sponsors (2)

Lead Sponsor	Collaborator
British Columbia Cancer Agency	BC Cancer Foundation

Country where clinical trial is conducted

Canada, 

References & Publications (4)

Jamshidi F, Pleasance E, Li Y, Shen Y, Kasaian K, Corbett R, Eirew P, Lum A, Pandoh P, Zhao Y, Schein JE, Moore RA, Rassekh R, Huntsman DG, Knowling M, Lim H, Renouf DJ, Jones SJ, Marra MA, Nielsen TO, Laskin J, Yip S. Diagnostic value of next-generation sequencing in an unusual sphenoid tumor. Oncologist. 2014 Jun;19(6):623-30. doi: 10.1634/theoncologist.2013-0390. Epub 2014 May 7. — View Citation

Jones SJ, Laskin J, Li YY, Griffith OL, An J, Bilenky M, Butterfield YS, Cezard T, Chuah E, Corbett R, Fejes AP, Griffith M, Yee J, Martin M, Mayo M, Melnyk N, Morin RD, Pugh TJ, Severson T, Shah SP, Sutcliffe M, Tam A, Terry J, Thiessen N, Thomson T, Varhol R, Zeng T, Zhao Y, Moore RA, Huntsman DG, Birol I, Hirst M, Holt RA, Marra MA. Evolution of an adenocarcinoma in response to selection by targeted kinase inhibitors. Genome Biol. 2010;11(8):R82. doi: 10.1186/gb-2010-11-8-r82. Epub 2010 Aug 9. — View Citation

Laskin J, Jones S, Aparicio S, Chia S, Ch'ng C, Deyell R, Eirew P, Fok A, Gelmon K, Ho C, Huntsman D, Jones M, Kasaian K, Karsan A, Leelakumari S, Li Y, Lim H, Ma Y, Mar C, Martin M, Moore R, Mungall A, Mungall K, Pleasance E, Rassekh SR, Renouf D, Shen Y, Schein J, Schrader K, Sun S, Tinker A, Zhao E, Yip S, Marra MA. Lessons learned from the application of whole-genome analysis to the treatment of patients with advanced cancers. Cold Spring Harb Mol Case Stud. 2015 Oct;1(1):a000570. doi: 10.1101/mcs.a000570. — View Citation

Skamene T, Siu LL, Renouf DJ, Laskin JJ, Bedard PL, Jones SJM, Ferrario C, Whitlock J, Petrie J, Sullivan P, Malone ER, Nomikos D, Chen BE, Dancey Y. Canadian profiling and targeted agent utilization trial (CAPTUR/PM.1): A phase II basket precision medicine trial. J Clin Oncol. 2018;36(15), TPS12127. doi:10.1200/JCO.2018.36.15_suppl.TPS12127

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Influence of genomic data on clinical decision-making	This outcome will allow us to study how often in-depth genomic data impacts on clinical decision-making in a general oncology population. It will help describe how useful or important this sort of data is in daily practice.	5 years
Primary	Cataloging of cancer genomes	Accumulation of genomic information linked to treatment/outcome data will greatly enhance our knowledge and understanding of cancers and response to treatment.	5 years