Utilization of Genomic Information to Augment Chemotherapy Decision-making for People With Incurable Malignancies

Most systemic therapies are chosen on the basis of large randomized clinical trials; however, tumour heterogeneity means that cancers with similar histological features may have substantially different underlying biological drivers. The investigators propose that applying personal genomic information prospectively obtained in a clinically realistic timeframe to assist in chemotherapy decision-making could result in more effective and efficient cancer treatment. This study will investigate this approach in a cross section of advanced cancers to examine timeliness, deliverability, rate of actionable targets identified, and our ability to expand this approach into a larger clinical trial setting.

Study Overview

• Status: Completed
• Conditions: Advanced Incurable Cancers
• Intervention / Treatment: Genetic: in depth genomic sequencing

Detailed Description

It is clear that carcinogenesis is an immensely complex process and that even within a histologic cancer subtype - such as adenocarcinoma of the lung or breast - there is significant heterogeneity in cancer behaviour and response to therapy. Recognizing genetic mutations 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.

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. With many recognized mutations personalized evaluation of the genetic signature encoded in DNA and RNA may enable directed therapy to the appropriate oncologic pathway thereby providing information to help guide chemotherapy choices.

• Study Type: Interventional
• Enrollment (Actual): 100
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada
      • BC Cancer Agency

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Subjects must have histologically or cytologically confirmed diagnosis of cancer
2. This cancer must be incurable, as defined by their treating oncologist (generally because of advanced stage).
3. Subjects must agree to provide archival tissue and agree to undergo a study specific biopsy and blood test for genetic analysis. All subjects would have a biopsy and blood samples at progression if it could be done safely.
4. ECOG PS 0 or 1.
5. Age > 18 years of age.
6. Subject consent must be obtained according to the BCCA requirements.
7. Subject must be accessible for treatment and follow-up. Subjects must be registered at the BCCA Vancouver site.

Exclusion Criteria:

1. Unable or unwilling to undergo tumour biopsy(s) and/or blood/skin samples for normal DNA.
2. Significant medical condition that in the opinion of the treating oncologist renders the subject not suitable for participation.

Study Plan

How is the study designed?

Design Details

• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sequenced patients; Patients enrolled on the study who have successful sequencing of their cancers will be closely monitored for: what chemotherapy agents are next used, what response and toxicity do they have, is there any early sign of response detected on PET-CT, overall did the genomic information change treatment decision-making.	Genetic: in depth genomic sequencing; Fresh tumour biopsies and matched normal specimens (blood and surrounding tissue) and when possible archival pretreatment specimens, will undergo in depth DNA and RNA sequencing and analysis on an oncogene panel.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Frequency of actioanble genomic abnormalites detected that modify treatment	What is the frequency of "actionable" results in this varied tumour population ?	up to 24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
What is the frequency with which these actionable results actually result in a subject receiving a drug(s) related to this test	What is the frequency with which these actionable results actually result in a subject receiving a drug(s) related to this test.	up to 24 months

Collaborators and Investigators

• Sponsor: British Columbia Cancer Agency
• Collaborators: BC Cancer Foundation
• Investigators: Principal Investigator: Janessa J. Laskin, MD FRCPC, British Columbia Cancer Agency; Principal Investigator: Marco Marra, PhD FRSC, Genome Sciences Centre, BC Cancer Agency

Publications and helpful links

General Publications

• Peixoto RD; Li Y; Pleasance E; Yip S; et al. A case of the utilization of genomic information in the management of metastatic colorectal cancer. J Clin Oncol 30: 2012 (suppl 34; abstr 444)

Study record dates

Study Major Dates

• Study Start: June 1, 2012
• Primary Completion (Actual): February 1, 2015
• Study Completion (Actual): February 1, 2015

Study Registration Dates

• First Submitted: February 27, 2013
• First Submitted That Met QC Criteria: March 1, 2013
• First Posted (Estimate): March 4, 2013

Study Record Updates

• Last Update Posted (Estimate): February 5, 2015
• Last Update Submitted That Met QC Criteria: February 4, 2015
• Last Verified: February 1, 2013

More Information

Terms related to this study

• Keywords: metastatic cancer; adults; neoplasm; cancer genome; genomic analysis
• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: BCCA POG 01