Using Tumour DNA and Proteins to Better Understand How Pancreatic Cancer Responds to Treatment

Official title

Accelerating the Actionability of Treatment in Resected and Locally Advanced Pancreatic Cancer

Overview

The goal of this study is to learn if the genetic information and proteins from tumours can help treat pancreatic ductal adenocarcinoma (PDAC). The main questions it aims to answer are: * Is it feasible to obtain genetic test results within a timeframe that can help inform treatment decisions for individuals with PDAC? * Can the genetic test results provide information about how a tumour will respond to or resist treatment? Participants will: * Receive standard chemotherapy to treat their cancer. * Provide samples of their blood, tissue, and fluid for genetic testing. * Visit the clinic every 4 weeks for check-ups and tests. * Complete questionnaires every 12 weeks.

Interventions

• Genetic Genetic testing
  Analyses of the deoxyribonucleic acid (DNA), ribonucleic acid (RNA), proteins, and other molecules in the sample.
• Procedure Optional biopsy
  Optional collection of tumour tissue and normal tissue after the last dose of treatment.
• Procedure Tissue collection
  Collection of tumour tissue and normal tissue from biopsy or standard resection surgery prior to the first dose of treatment.

Primary outcome measures

• Frequency of comprehensive genomic results returned within 8 weeks of sample collection. [Time frame: From the date of resection surgery or baseline ctDNA collection until genomic results are available (typically 8 weeks).]

Secondary outcome measures (5)

• Overall response rate (ORR) in each study arm, as defined by Response Evaluation Criteria in Solid Tumours (RECIST) 1.1 [Time frame: From the date of the baseline scan (within 28 days of first dose) until the date of confirmed progression, withdrawal, date of death, or end of study, whichever comes first, assessed up to 72 months.]
• Disease control rate in each study arm, as defined by RECIST 1.1 [Time frame: From the date of the baseline scan (within 28 days of first dose) until the date of confirmed progression, withdrawal, date of death, or end of study, whichever comes first, assessed up to 72 months.]
• Duration of response (DoR) in each study arm, as defined by RECIST 1.1 [Time frame: From the first date of CR or PR until the first date of confirmed progression, withdrawal, date of death, or end of study, whichever comes first, assessed up to 72 months.]
• Progression-free survival (PFS) in each study arm from the initiation of chemotherapy [Time frame: From the date of first dose of chemotherapy until the date of confirmed progression, withdrawal, date of death, or end of study, whichever comes first, assessed up to 72 months.]
• Overall survival (OS) in each study arm from the initiation of chemotherapy [Time frame: From the date of first dose of chemotherapy until the date of death or end of study, whichever comes first, assessed up to 72 months.]]

Eligibility criteria

Inclusion criteria

Participants must meet all of the following criteria prior to Pre-Baseline registration:

• Age 18 years or older.
• Histological or radiological diagnosis of resectable, borderline resectable, or locally advanced PDAC.
• Medically fit and planned to undergo laparoscopic procedure as part of standard of care.
• Able to give informed consent for the study-related procedures performed during laparoscopy.

Participants must meet all of the following criteria to be eligible for enrollment in the Main Study:

• Age 18 years or older.
• Enrolled in the Personalized Oncogenomics (POG) Program at BC Cancer.
• Histological and/or radiological diagnosis of resectable, borderline resectable, or locally advanced PDAC. Participants without a histological diagnosis of PDAC must undergo confirmatory histological diagnosis prior to treatment start date.
• Medically fit to undergo surgical resection of the primary lesion(s) as judged by the investigator (Resectable and Borderline Resectable Cohorts only).
• Planned for adjuvant (Resectable and Borderline Resectable Cohorts) or first-line (Locally Advanced Cohort) therapy with FOLFIRINOX or a gemcitabine-based regimen, either as part of routine care or in combination with an investigational agent(s) within another clinical trial. Participants may have received pre-operative therapy.
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1.
• Adequate organ function as defined by the following laboratory results obtained within 28 days prior to enrollment date:

• Absolute neutrophil count (ANC) ≥ 1.5 x 10\^9/L.
• Hemoglobin ≥ 9 g/dL.
• Platelets ≥ 75 x 10\^9/L.
• Prothrombin time test and international normalized ratio (PT/INR) and partial thromboplastin time (PTT) ≤ 1.5 x Upper Limit of Normal (ULN).
• Total bilirubin ≤ 1.5 x ULN. Isolated bilirubin > 1.5 x ULN is acceptable if bilirubin is fractionated and direct bilirubin < 35%.
• Aspartate aminotransferase (AST) and alanine aminotransferase (AST) ≤ 1.5 x ULN. If liver metastases are present, AST and ALT ≤ 5 x ULN is permitted.
• Albumin ≥ 25 g/L.
• One of the following:

• Creatinine ≤ 1.5 x ULN.
• Calculated creatinine clearance (as calculated by Cockcroft-Gault formula) ≥ 40 mL/min.
• 24-hour urine creatinine clearance ≥ 40 mL/min.
• Life expectancy greater than 90 days as judged by the investigator.
• Able to give informed consent for the study procedures defined in this protocol.
• Measurable disease by RECIST 1.1. For those in the Resectable and Borderline Resectable Cohorts, measurable disease must be present prior to resection surgery.

Exclusion criteria

• Presence of distant or lymph node metastases. Individuals with metastatic PDAC are not eligible.
• Currently receiving adjuvant (Resectable and Borderline Resectable Cohorts) or systemic (Locally Advanced Cohort) anti-cancer therapy (chemotherapy or any other anti-cancer agent) with one exception: pre-operative therapy is permitted.
• Not fit for chemotherapy as judged by the investigator.
• Presence of brain metastases.
• Positive pregnancy test.
• Unable to comply with the study assessments and procedures defined in this protocol.
• Individuals who are otherwise judged by the investigator to be unfit to proceed with this protocol.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Basic science

Study locations

Canada · 1 center

• BC Cancer — Vancouver

Publications

• Strickler JH, Satake H, George TJ, Yaeger R, Hollebecque A, Garrido-Laguna I, Schuler M, Burns TF, Coveler AL, Falchook GS, Vincent M, Sunakawa Y, Dahan L, Bajor D, Rha SY, Lemech C, Juric D, Rehn M, Ngarmchamnanrith G, Jafarinasabian P, Tran Q, Hong DS. Sotorasib in KRAS p.G12C-Mutated Advanced Pancreatic Cancer. N Engl J Med. 2023 Jan 5;388(1):33-43. doi: 10.1056/NEJMoa2208470. Epub 2022 Dec 21. PMID 36546651
• Wong HL, Zhao EY, Jones MR, Reisle CR, Eirew P, Pleasance E, Grande BM, Karasinska JM, Kalloger SE, Lim HJ, Shen Y, Yip S, Morin RD, Laskin J, Marra MA, Jones SJM, Schrader KA, Schaeffer DF, Renouf DJ. Temporal Dynamics of Genomic Alterations in a BRCA1 Germline-Mutated Pancreatic Cancer With Low Genomic Instability Burden but Exceptional Response to Fluorouracil, Oxaliplatin, Leucovorin, and Irin PMID 32913994
• O'Kane GM, Grunwald BT, Jang GH, Masoomian M, Picardo S, Grant RC, Denroche RE, Zhang A, Wang Y, Lam B, Krzyzanowski PM, Lungu IM, Bartlett JMS, Peralta M, Vyas F, Khokha R, Biagi J, Chadwick D, Ramotar S, Hutchinson S, Dodd A, Wilson JM, Notta F, Zogopoulos G, Gallinger S, Knox JJ, Fischer SE. GATA6 Expression Distinguishes Classical and Basal-like Subtypes in Advanced Pancreatic Cancer. Clin Can PMID 32156747
• Aung KL, Fischer SE, Denroche RE, Jang GH, Dodd A, Creighton S, Southwood B, Liang SB, Chadwick D, Zhang A, O'Kane GM, Albaba H, Moura S, Grant RC, Miller JK, Mbabaali F, Pasternack D, Lungu IM, Bartlett JMS, Ghai S, Lemire M, Holter S, Connor AA, Moffitt RA, Yeh JJ, Timms L, Krzyzanowski PM, Dhani N, Hedley D, Notta F, Wilson JM, Moore MJ, Gallinger S, Knox JJ. Genomics-Driven Precision Medicine PMID 29288237
• Neoptolemos JP, Palmer DH, Ghaneh P, Psarelli EE, Valle JW, Halloran CM, Faluyi O, O'Reilly DA, Cunningham D, Wadsley J, Darby S, Meyer T, Gillmore R, Anthoney A, Lind P, Glimelius B, Falk S, Izbicki JR, Middleton GW, Cummins S, Ross PJ, Wasan H, McDonald A, Crosby T, Ma YT, Patel K, Sherriff D, Soomal R, Borg D, Sothi S, Hammel P, Hackert T, Jackson R, Buchler MW; European Study Group for Pancrea PMID 28129987
• Garcea G, Dennison AR, Pattenden CJ, Neal CP, Sutton CD, Berry DP. Survival following curative resection for pancreatic ductal adenocarcinoma. A systematic review of the literature. JOP. 2008 Mar 8;9(2):99-132. PMID 18326920
• Brenner DR, Poirier A, Woods RR, Ellison LF, Billette JM, Demers AA, Zhang SX, Yao C, Finley C, Fitzgerald N, Saint-Jacques N, Shack L, Turner D, Holmes E; Canadian Cancer Statistics Advisory Committee. Projected estimates of cancer in Canada in 2022. CMAJ. 2022 May 2;194(17):E601-E607. doi: 10.1503/cmaj.212097. PMID 35500919
• Jones MR, Williamson LM, Topham JT, Lee MKC, Goytain A, Ho J, Denroche RE, Jang G, Pleasance E, Shen Y, Karasinska JM, McGhie JP, Gill S, Lim HJ, Moore MJ, Wong HL, Ng T, Yip S, Zhang W, Sadeghi S, Reisle C, Mungall AJ, Mungall KL, Moore RA, Ma Y, Knox JJ, Gallinger S, Laskin J, Marra MA, Schaeffer DF, Jones SJM, Renouf DJ. NRG1 Gene Fusions Are Recurrent, Clinically Actionable Gene Rearrangements PMID 31068372

Identifiers

NCT: NCT06574620 · H24-01809

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗