Liquid Biopsy Evaluation and Repository Development at Princess Margaret

NCT03702309RecruitingOBSERVATIONAL

Summary

The objective of this protocol is to develop an institution-wide liquid biopsy protocol that will establish a common process for collecting blood and corresponding archived tumor specimens for future research studies at the University Health Network's Princess Margaret Cancer Centre. Circulating cell-free nucleic acids (cfNA), including cell-free DNA (cfDNA) and cell-free RNA (cfRNA), are non-invasive, real-time biomarkers that can provide diagnostic and prognostic information before cancer diagnosis, during cancer treatment, and at disease progression. Cancer research scientists and clinicians at the Princess Margaret are interested in incorporating the collection of peripheral blood samples ("liquid biopsies") into research protocols as a means of non-invasively assessing tumor progression and response to treatment at multiple time points during a patient's course of disease.

Key Facts

Lead Sponsor

University Health Network, Toronto

Enrollment

2500

Start Date

2017-08-03

Completion Date

2026-07-06

Study Type

OBSERVATIONAL

Official Title

Liquid Biopsy Evaluation and Repository Development at Princess Margaret

Conditions

CancerBreast CancerLung CancerColon CancerOvarian CancerMelanomaLymphomaLeukemiaMutationLynch SyndromeCowden SyndromeBRCA1 MutationBRCA2 MutationUterine CancerMyelomaKidney CancerHead and Neck CancerMeningioma

Eligibility

Age Range

18 Years+

Sex

ALL

Inclusion Criteria:

1. Patients with either histological confirmation of a solid tumor or hematological malignancy, OR patients identified as high-risk for cancer (based on identified aberration in cancer predisposition gene or on hormonal and/or family history without known aberration).
2. Patient must be ≥ 18 years old.
3. All patients must have signed and dated an informed consent form for this LIBERATE study.
4. If patients are being co-consented for a separate primary research study listed in Appendix I, they must fulfill the eligibility criteria for that separate primary research study. If there is a discrepancy in the eligibility criteria between protocols, the separate primary research study's criteria take precedence.

Exclusion Criteria:

None

Outcome Measures

Primary Outcomes

Collection and annotation of biospecimens

Facilitate and streamline the collection, banking, and annotation of biospecimens (especially liquid biopsy specimens and optionally corresponding archived tumor specimens) for research studies across the University Health Network institution

Time frame: Through study completion, up to 5 years

Secondary Outcomes

Electronic Consenting

Implement an electronic informed consent process for clinical research at the Princess Margaret Cancer Centre

Time frame: Through study completion, up to 5 years

Correlative Studies Questionnaire

Collect observational/epidemiological data using a Correlative Studies Questionnaire for clinical annotation of specimens and future research use. Data collected involves demographics such as family history, medical history, smoking history, and lifestyle.

Time frame: Through study completion, up to 5 years

Locations

Princess Margaret Cancer Centre, Toronto, Canada

Linked Papers

2023-11-16

Clinical Validation of Human Papilloma Virus Circulating Tumor DNA for Early Detection of Residual Disease After Chemoradiation in Cervical Cancer

PURPOSE Most cervical cancers are caused by human papilloma virus (HPV), and HPV circulating tumor DNA (ctDNA) may identify patients at highest risk of relapse. Our pilot study using digital polymerase chain reaction (dPCR) showed that detectable HPV ctDNA at the end of chemoradiation (CRT) is associated with inferior progression-free survival (PFS) and that a next-generation sequencing approach (HPV-seq) may outperform dPCR. We aimed to prospectively validate HPV ctDNA as a tool for early detection of residual disease. METHODS This prospective, multicenter validation study accrued patients with stage IB-IVA cervical cancer treated with CRT between 2017 and 2022. Participants underwent phlebotomy at baseline, end of CRT, 4-6 weeks post-CRT, and 3 months post-CRT for HPV ctDNA levels. Plasma HPV genotype–specific DNA levels were quantified using both dPCR and HPV-seq. The primary end point was 2-year PFS. RESULTS With a median follow-up of 2.2 (range, 0.5-5.5) years, there were 24 PFS events among the 70 patients with HPV+ cervical cancer. Patients with detectable HPV ctDNA on dPCR at the end of CRT, 4-6 weeks post-CRT, and 3 months post-CRT had significantly worse 2-year PFS compared with those with undetectable HPV ctDNA (77% v 51%, P = .03; 82% v 15%, P < .001; and 82% v 24%, P < .001, respectively); the median lead time to recurrence was 5.9 months. HPV-seq showed similar results as dPCR. On multivariable analyses, detectable HPV ctDNA on dPCR and HPV-seq remained independently associated with inferior PFS. CONCLUSION Persistent HPV ctDNA after CRT is independently associated with inferior PFS. HPV ctDNA testing can identify, as early as at the end of CRT, patients at high risk of recurrence for future treatment intensification trials.

Linked Investigators

Andra Nica

Anthony Fyles

Elizabeth Barnes

Jennifer Croke

Kathy Han

Michael Milosevic

Sarah E. Ferguson

Scott V. Bratman

Stephanie Lheureux

Ur Metser

Zeynep Baskurt