Clinical trial NCT05234177: Tempus CRC Surveillance Study: A ctDNA Biomarker Profiling Study of Patients With CRC Using NGS Assays
Official title: Tempus CRC Surveillance Study: A Longitudinal Circulating Tumor DNA (ctDNA) Biomarker Profiling Study of Patients With Colorectal Cancer (CRC) Using Comprehensive Next-Generation Sequencing (NGS)Assays
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Colorectal Cancer
Keywords: Cancer
Oncology
Observational
Genomic Profiling
Precision medicine
CRC
Colorectal Cancer
NGS
Biomarkers
Lead sponsor: Tempus AI
Sponsor class: INDUSTRY
First posted: 2022-02-10
Enrollment: 300
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: This protocol targets patients with colorectal cancer (CRC), stage I-IVA disease

Brief summary: The study is an observational multicenter evaluation of participants with colorectal cancer (CRC) who will receive longitudinal plasma ctDNA biomarker profiling in addition to their standard-of-care therapy and disease surveillance.


Eligibility criteria: Inclusion Criteria:

* Known or suspected colorectal adenocarcinoma (Stage I to IVA disease)
* Planning to undergo or has undergone a surgical resection for suspected adenocarcinoma of the colon or rectum with curative intent.
* 18 years old or older
* Willing and able to provide informed consent
* Willing to have additional blood samples collected during routine surveillance visits

Exclusion Criteria:

* Not willing to have additional blood samples collected
* Pathology that is not consistent with colorectal adenocarcinoma

Primary outcomes:
measure: Recurrence-Free Survival
timeFrame: 2 years
Secondary outcomes:
measure: Sensitivity
timeFrame: 2 years
measure: Specificity
timeFrame: 2 years
measure: Positive Predictive Value
timeFrame: 2 years
Other outcomes:
measure: Overall Survival
timeFrame: 2 years or until the patient is reported deceased
measure: Lead Time
timeFrame: 2 years
Locations:
city: Fort Smith
country: United States
facility: Mercy Clinic Oncology - Fort Smith
state: Arkansas
city: Fountain Valley
country: United States
facility: MemorialCare
state: California
city: Bethesda
country: United States
facility: The Center for Cancer and Blood Disorders
state: Maryland
city: Joplin
country: United States
facility: Mercy Clinic Oncology and Hematology - Joplin
state: Missouri
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Saint Louis
country: United States
facility: Mercy Clinic Oncology and Hematology - Sindelar Cancer Center
state: Missouri
city: Saint Louis
country: United States
facility: Mercy Clinic Oncology and Hematology - David C. Pratt Cancer Center
state: Missouri
city: Springfield
country: United States
facility: Mercy Clinic Cancer and Hematology - Chub O'Reilly Cancer Center
state: Missouri
city: Omaha
country: United States
facility: Nebraska Cancer Specialists
state: Nebraska
city: Goldsboro
country: United States
facility: Southeastern Medical Oncology Center
state: North Carolina
city: Canton
country: United States
facility: Aultman Hospital
state: Ohio
city: Cincinnati
country: United States
facility: TriHealth Cancer Institute
state: Ohio
city: Columbus
country: United States
facility: Ohio State University
state: Ohio
city: Columbus
country: United States
facility: OhioHealth Research Institute
state: Ohio
city: Toledo
country: United States
facility: Toledo Clinic Cancer Center
state: Ohio
city: Oklahoma City
country: United States
facility: Mercy Clinic Oncology and Hematology - Coletta
state: Oklahoma
city: York
country: United States
facility: Cancer Care Associates of York
state: Pennsylvania
city: Salt Lake City
country: United States
facility: Utah Cancer Specialists
state: Utah
city: Seattle
country: United States
facility: University of Washington / Fred Hutchinson Cancer Center
state: Washington
city: Appleton
country: United States
facility: ThedaCare Regional Cancer Center
state: Wisconsin
Study officials:
affiliation: Tempus AI, Inc.
name: Kristiyana Kaneva, MD, MS
role: PRINCIPAL_INVESTIGATOR
References:
citation: Siegel RL, Miller KD, Jemal A. Cancer statistics, 2019. CA Cancer J Clin. 2019 Jan;69(1):7-34. doi: 10.3322/caac.21551. Epub 2019 Jan 8.
citation: Siegel RL, Miller KD, Goding Sauer A, Fedewa SA, Butterly LF, Anderson JC, Cercek A, Smith RA, Jemal A. Colorectal cancer statistics, 2020. CA Cancer J Clin. 2020 May;70(3):145-164. doi: 10.3322/caac.21601. Epub 2020 Mar 5.
citation: Stoffel EM, Murphy CC. Epidemiology and Mechanisms of the Increasing Incidence of Colon and Rectal Cancers in Young Adults. Gastroenterology. 2020 Jan;158(2):341-353. doi: 10.1053/j.gastro.2019.07.055. Epub 2019 Aug 5.
citation: Islami F, Ward EM, Sung H, Cronin KA, Tangka FKL, Sherman RL, Zhao J, Anderson RN, Henley SJ, Yabroff KR, Jemal A, Benard VB. Annual Report to the Nation on the Status of Cancer, Part 1: National Cancer Statistics. J Natl Cancer Inst. 2021 Nov 29;113(12):1648-1669. doi: 10.1093/jnci/djab131.
citation: Brenner H, Kloor M, Pox CP. Colorectal cancer. Lancet. 2014 Apr 26;383(9927):1490-1502. doi: 10.1016/S0140-6736(13)61649-9. Epub 2013 Nov 11.
citation: Institute NC, National Cancer Institute. AJCC Cancer Staging Manual 8th Edition. Definitions. 2020
citation: Leufkens AM, van den Bosch MA, van Leeuwen MS, Siersema PD. Diagnostic accuracy of computed tomography for colon cancer staging: a systematic review. Scand J Gastroenterol. 2011 Jul;46(7-8):887-94. doi: 10.3109/00365521.2011.574732. Epub 2011 Apr 20.
citation: Benson AB 3rd, Choti MA, Cohen AM, Doroshow JH, Fuchs C, Kiel K, Martin EW Jr, McGinn C, Petrelli NJ, Posey JA, Skibber JM, Venook A, Yeatman TJ; National Comprehensive Cancer Network. NCCN Practice Guidelines for Colorectal Cancer. Oncology (Williston Park). 2000 Nov;14(11A):203-12.
citation: Kahi CJ, Boland CR, Dominitz JA, Giardiello FM, Johnson DA, Kaltenbach T, Lieberman D, Levin TR, Robertson DJ, Rex DK; United States Multi-Society Task Force on Colorectal Cancer. Colonoscopy Surveillance After Colorectal Cancer Resection: Recommendations of the US Multi-Society Task Force on Colorectal Cancer. Gastroenterology. 2016 Mar;150(3):758-768.e11. doi: 10.1053/j.gastro.2016.01.001. Epub 2016 Feb 10.
citation: Winawer SJ, Fletcher RH, Miller L, Godlee F, Stolar MH, Mulrow CD, Woolf SH, Glick SN, Ganiats TG, Bond JH, Rosen L, Zapka JG, Olsen SJ, Giardiello FM, Sisk JE, Van Antwerp R, Brown-Davis C, Marciniak DA, Mayer RJ. Colorectal cancer screening: clinical guidelines and rationale. Gastroenterology. 1997 Feb;112(2):594-642. doi: 10.1053/gast.1997.v112.agast970594. No abstract available.
citation: Provenzale D, Ness RM, Llor X, Weiss JM, Abbadessa B, Cooper G, Early DS, Friedman M, Giardiello FM, Glaser K, Gurudu S, Halverson AL, Issaka R, Jain R, Kanth P, Kidambi T, Lazenby AJ, Maguire L, Markowitz AJ, May FP, Mayer RJ, Mehta S, Patel S, Peter S, Stanich PP, Terdiman J, Keller J, Dwyer MA, Ogba N. NCCN Guidelines Insights: Colorectal Cancer Screening, Version 2.2020. J Natl Compr Canc Netw. 2020 Oct 1;18(10):1312-1320. doi: 10.6004/jnccn.2020.0048.
citation: Ladabaum U, Dominitz JA, Kahi C, Schoen RE. Strategies for Colorectal Cancer Screening. Gastroenterology. 2020 Jan;158(2):418-432. doi: 10.1053/j.gastro.2019.06.043. Epub 2019 Aug 5.
citation: Muller MF, Ibrahim AE, Arends MJ. Molecular pathological classification of colorectal cancer. Virchows Arch. 2016 Aug;469(2):125-34. doi: 10.1007/s00428-016-1956-3. Epub 2016 Jun 20.
citation: Poulogiannis G, Ichimura K, Hamoudi RA, Luo F, Leung SY, Yuen ST, Harrison DJ, Wyllie AH, Arends MJ. Prognostic relevance of DNA copy number changes in colorectal cancer. J Pathol. 2010 Feb;220(3):338-47. doi: 10.1002/path.2640.
citation: Arends MJ. Pathways of colorectal carcinogenesis. Appl Immunohistochem Mol Morphol. 2013 Mar;21(2):97-102. doi: 10.1097/PAI.0b013e31827ea79e.
citation: Poulogiannis G, Frayling IM, Arends MJ. DNA mismatch repair deficiency in sporadic colorectal cancer and Lynch syndrome. Histopathology. 2010 Jan;56(2):167-79. doi: 10.1111/j.1365-2559.2009.03392.x.
citation: Giardiello FM, Allen JI, Axilbund JE, Boland CR, Burke CA, Burt RW, Church JM, Dominitz JA, Johnson DA, Kaltenbach T, Levin TR, Lieberman DA, Robertson DJ, Syngal S, Rex DK. Guidelines on genetic evaluation and management of Lynch syndrome: a consensus statement by the US Multi-Society Task Force on Colorectal Cancer. Dis Colon Rectum. 2014 Aug;57(8):1025-48. doi: 10.1097/DCR.000000000000000.
citation: Domingo E, Niessen RC, Oliveira C, Alhopuro P, Moutinho C, Espin E, Armengol M, Sijmons RH, Kleibeuker JH, Seruca R, Aaltonen LA, Imai K, Yamamoto H, Schwartz S Jr, Hofstra RM. BRAF-V600E is not involved in the colorectal tumorigenesis of HNPCC in patients with functional MLH1 and MSH2 genes. Oncogene. 2005 Jun 2;24(24):3995-8. doi: 10.1038/sj.onc.1208569.
citation: Morse MA, Hochster H, Benson A. Perspectives on Treatment of Metastatic Colorectal Cancer with Immune Checkpoint Inhibitor Therapy. Oncologist. 2020 Jan;25(1):33-45. doi: 10.1634/theoncologist.2019-0176. Epub 2019 Aug 5.
citation: Overman MJ, McDermott R, Leach JL, Lonardi S, Lenz HJ, Morse MA, Desai J, Hill A, Axelson M, Moss RA, Goldberg MV, Cao ZA, Ledeine JM, Maglinte GA, Kopetz S, Andre T. Nivolumab in patients with metastatic DNA mismatch repair-deficient or microsatellite instability-high colorectal cancer (CheckMate 142): an open-label, multicentre, phase 2 study. Lancet Oncol. 2017 Sep;18(9):1182-1191. doi: 10.1016/S1470-2045(17)30422-9. Epub 2017 Jul 19.
citation: Rotte A. Combination of CTLA-4 and PD-1 blockers for treatment of cancer. J Exp Clin Cancer Res. 2019 Jun 13;38(1):255. doi: 10.1186/s13046-019-1259-z.
citation: Gourd E. Nivolumab plus ipilimumab in metastatic colorectal cancer. Lancet Oncol. 2018 Mar;19(3):e139. doi: 10.1016/S1470-2045(18)30067-6. Epub 2018 Jan 26. No abstract available.
citation: Overman MJ, Lonardi S, Wong KYM, Lenz HJ, Gelsomino F, Aglietta M, Morse MA, Van Cutsem E, McDermott R, Hill A, Sawyer MB, Hendlisz A, Neyns B, Svrcek M, Moss RA, Ledeine JM, Cao ZA, Kamble S, Kopetz S, Andre T. Durable Clinical Benefit With Nivolumab Plus Ipilimumab in DNA Mismatch Repair-Deficient/Microsatellite Instability-High Metastatic Colorectal Cancer. J Clin Oncol. 2018 Mar 10;36(8):773-779. doi: 10.1200/JCO.2017.76.9901. Epub 2018 Jan 20.
citation: Noffsinger AE. Serrated polyps and colorectal cancer: new pathway to malignancy. Annu Rev Pathol. 2009;4:343-64. doi: 10.1146/annurev.pathol.4.110807.092317.
citation: Kopetz S, Grothey A, Yaeger R, Van Cutsem E, Desai J, Yoshino T, Wasan H, Ciardiello F, Loupakis F, Hong YS, Steeghs N, Guren TK, Arkenau HT, Garcia-Alfonso P, Pfeiffer P, Orlov S, Lonardi S, Elez E, Kim TW, Schellens JHM, Guo C, Krishnan A, Dekervel J, Morris V, Calvo Ferrandiz A, Tarpgaard LS, Braun M, Gollerkeri A, Keir C, Maharry K, Pickard M, Christy-Bittel J, Anderson L, Sandor V, Tabernero J. Encorafenib, Binimetinib, and Cetuximab in BRAF V600E-Mutated Colorectal Cancer. N Engl J Med. 2019 Oct 24;381(17):1632-1643. doi: 10.1056/NEJMoa1908075. Epub 2019 Sep 30.
citation: Lievre A, Bachet JB, Boige V, Cayre A, Le Corre D, Buc E, Ychou M, Bouche O, Landi B, Louvet C, Andre T, Bibeau F, Diebold MD, Rougier P, Ducreux M, Tomasic G, Emile JF, Penault-Llorca F, Laurent-Puig P. KRAS mutations as an independent prognostic factor in patients with advanced colorectal cancer treated with cetuximab. J Clin Oncol. 2008 Jan 20;26(3):374-9. doi: 10.1200/JCO.2007.12.5906.
citation: Douillard JY, Oliner KS, Siena S, Tabernero J, Burkes R, Barugel M, Humblet Y, Bodoky G, Cunningham D, Jassem J, Rivera F, Kocakova I, Ruff P, Blasinska-Morawiec M, Smakal M, Canon JL, Rother M, Williams R, Rong A, Wiezorek J, Sidhu R, Patterson SD. Panitumumab-FOLFOX4 treatment and RAS mutations in colorectal cancer. N Engl J Med. 2013 Sep 12;369(11):1023-34. doi: 10.1056/NEJMoa1305275.
citation: Lai E, Liscia N, Donisi C, Mariani S, Tolu S, Pretta A, Persano M, Pinna G, Balconi F, Pireddu A, Impera V, Dubois M, Migliari M, Spanu D, Saba G, Camera S, Musio F, Ziranu P, Puzzoni M, Demurtas L, Pusceddu V, Dettori M, Massa E, Atzori F, Dessi M, Astara G, Madeddu C, Scartozzi M. Molecular-Biology-Driven Treatment for Metastatic Colorectal Cancer. Cancers (Basel). 2020 May 13;12(5):1214. doi: 10.3390/cancers12051214.
citation: Normanno N, Cervantes A, Ciardiello F, De Luca A, Pinto C. The liquid biopsy in the management of colorectal cancer patients: Current applications and future scenarios. Cancer Treat Rev. 2018 Nov;70:1-8. doi: 10.1016/j.ctrv.2018.07.007. Epub 2018 Jul 18.
citation: Siravegna G, Marsoni S, Siena S, Bardelli A. Integrating liquid biopsies into the management of cancer. Nat Rev Clin Oncol. 2017 Sep;14(9):531-548. doi: 10.1038/nrclinonc.2017.14. Epub 2017 Mar 2.
citation: Crowley E, Di Nicolantonio F, Loupakis F, Bardelli A. Liquid biopsy: monitoring cancer-genetics in the blood. Nat Rev Clin Oncol. 2013 Aug;10(8):472-84. doi: 10.1038/nrclinonc.2013.110. Epub 2013 Jul 9.
citation: Kolencik D, Shishido SN, Pitule P, Mason J, Hicks J, Kuhn P. Liquid Biopsy in Colorectal Carcinoma: Clinical Applications and Challenges. Cancers (Basel). 2020 May 27;12(6):1376. doi: 10.3390/cancers12061376.
citation: Richman SD, Chambers P, Seymour MT, Daly C, Grant S, Hemmings G, Quirke P. Intra-tumoral heterogeneity of KRAS and BRAF mutation status in patients with advanced colorectal cancer (aCRC) and cost-effectiveness of multiple sample testing. Anal Cell Pathol (Amst). 2011;34(1-2):61-6. doi: 10.3233/ACP-2011-0005.
citation: Kasi PM, Sawyer S, Guilford J, Munro M, Ellers S, Wulff J, Hook N, Krinshpun S, Koyen Malashevich A, Malhotra M, Rodriguez A, Moshkevich S, Grothey A, Kopetz S, Billings P, Aleshin A. BESPOKE study protocol: a multicentre, prospective observational study to evaluate the impact of circulating tumour DNA guided therapy on patients with colorectal cancer. BMJ Open. 2021 Sep 24;11(9):e047831. doi: 10.1136/bmjopen-2020-047831.
citation: Hu Y, Ulrich BC, Supplee J, Kuang Y, Lizotte PH, Feeney NB, Guibert NM, Awad MM, Wong KK, Janne PA, Paweletz CP, Oxnard GR. False-Positive Plasma Genotyping Due to Clonal Hematopoiesis. Clin Cancer Res. 2018 Sep 15;24(18):4437-4443. doi: 10.1158/1078-0432.CCR-18-0143. Epub 2018 Mar 22.
citation: Parikh AR, Van Seventer EE, Siravegna G, Hartwig AV, Jaimovich A, He Y, Kanter K, Fish MG, Fosbenner KD, Miao B, Phillips S, Carmichael JH, Sharma N, Jarnagin J, Baiev I, Shah YS, Fetter IJ, Shahzade HA, Allen JN, Blaszkowsky LS, Clark JW, Dubois JS, Franses JW, Giantonio BJ, Goyal L, Klempner SJ, Nipp RD, Roeland EJ, Ryan DP, Weekes CD, Wo JY, Hong TS, Bordeianou L, Ferrone CR, Qadan M, Kunitake H, Berger D, Ricciardi R, Cusack JC, Raymond VM, Talasaz A, Boland GM, Corcoran RB. Minimal Residual Disease Detection using a Plasma-only Circulating Tumor DNA Assay in Patients with Colorectal Cancer. Clin Cancer Res. 2021 Oct 15;27(20):5586-5594. doi: 10.1158/1078-0432.CCR-21-0410. Epub 2021 Apr 29.
citation: Reinert T, Henriksen TV, Christensen E, Sharma S, Salari R, Sethi H, Knudsen M, Nordentoft I, Wu HT, Tin AS, Heilskov Rasmussen M, Vang S, Shchegrova S, Frydendahl Boll Johansen A, Srinivasan R, Assaf Z, Balcioglu M, Olson A, Dashner S, Hafez D, Navarro S, Goel S, Rabinowitz M, Billings P, Sigurjonsson S, Dyrskjot L, Swenerton R, Aleshin A, Laurberg S, Husted Madsen A, Kannerup AS, Stribolt K, Palmelund Krag S, Iversen LH, Gotschalck Sunesen K, Lin CJ, Zimmermann BG, Lindbjerg Andersen C. Analysis of Plasma Cell-Free DNA by Ultradeep Sequencing in Patients With Stages I to III Colorectal Cancer. JAMA Oncol. 2019 Aug 1;5(8):1124-1131. doi: 10.1001/jamaoncol.2019.0528.
citation: Beaubier N, Bontrager M, Huether R, Igartua C, Lau D, Tell R, Bobe AM, Bush S, Chang AL, Hoskinson DC, Khan AA, Kudalkar E, Leibowitz BD, Lozachmeur A, Michuda J, Parsons J, Perera JF, Salahudeen A, Shah KP, Taxter T, Zhu W, White KP. Integrated genomic profiling expands clinical options for patients with cancer. Nat Biotechnol. 2019 Nov;37(11):1351-1360. doi: 10.1038/s41587-019-0259-z. Epub 2019 Sep 30.
citation: Beaubier N, Tell R, Lau D, Parsons JR, Bush S, Perera J, Sorrells S, Baker T, Chang A, Michuda J, Iguartua C, MacNeil S, Shah K, Ellis P, Yeatts K, Mahon B, Taxter T, Bontrager M, Khan A, Huether R, Lefkofsky E, White KP. Clinical validation of the tempus xT next-generation targeted oncology sequencing assay. Oncotarget. 2019 Mar 22;10(24):2384-2396. doi: 10.18632/oncotarget.26797. eCollection 2019 Mar 22.