Gastric-Esophageal CancerSIGNAL GEC-101NCT07565857
Signatera-Guided De-escalation of Adjuvant Therapy in Resectable Stage II-IVa Gastric/Gastric-Esophageal Cancer
A study testing Signatera Genome ultra-sensitive ctDNA blood test in people with Gastric-Esophageal Cancer, run by Natera, Inc..
Trial summary
The goal of this clinical trial is to assess if circulating tumor DNA, as assessed by Signatera tumor-informed MRD assay, can guide de-escalation of adjuvant therapy in patients with resectable Stage II-IVa Gastric/Gastric-Esophageal Cancer. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Gastric-Esophageal Cancer
- What is being tested?
- Signatera Genome ultra-sensitive ctDNA blood test
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1,000 participants
- Where
- No sites listed yet
- Study dates
- Sep 2026to Sep 2034
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Signed and dated informed consent form (ICF) obtained prior to any trial-specific enrollment procedure.
- Age is ≥ 18 years-old at the time of ICF signature.
- Able to submit adequate archival tumor tissue (eg, 6 to 10 unstained slides at 10 microns (μm) each or 12-19 unstained slides at 5-microns (μm) plus one hematoxylin and eosin slide (see study lab manual) obtained per standard of care procedures for submission to a central laboratory for Signatera testing OR prior commercial Signatera Genome test results.
- Histologically confirmed adenocarcinoma of the stomach, esophagus and/or gastroesophageal junction (GEJ), resectable clinical Stage II-IVa per AJCC 9th edition.
- Completion of full or modified course (based on Dosing and Modification Guidelines) of neoadjuvant D-FLOT therapy (ie, two 4-week cycles of durvalumab, four 2-week cycles of FLOT) .
- Has undergone complete surgical resection of the gastric/GEJ tumor with pathologically confirmed negative margins (R0 resection).
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- Eligible to receive adjuvant D-FLOT treatment within 12 weeks postoperative per standard of care (SOC) as assessed by the treating clinician.
- Known statuses pertaining to randomization stratification factors:
- Post neoadjuvant, post-operative (yp) lymph node status and tumor staging (ypT1-3, N0 vs T4 or N+)
- Combined Positive Score ( ≥ 1 vs <1)Tumor PD-L1 status confirmed by immunohistochemistry/CPS score.
- Post neoadjuvant, post-operative major pathological response (MPR): Yes/No
- ECOG performance status 0-1.
- No evidence of disease by radiographic imaging.
- Must be willing to and able to comply with adjuvant treatment plans based on ctDNA results and other trial-mandated procedures.
- Women of child bearing potential must have a confirmed negative pregnancy test within 14 days of enrollment per institutional standards.
Who cannot join
- Histologic presence of adenosquamous cell carcinoma, squamous cell carcinoma, gastrointestinal stromal tumor, or neuroendocrine tumors.
- Radiographic evidence of unresectable metastatic disease (ie, IVb).
- Presence of peritoneal dissemination.
- Any prior therapy (eg, radiation, chemoradiation, chemotherapy) for gastric or gastroesophageal cancer other than neoadjuvant D-FLOT and R0 curative intent surgery.
- Known contradiction or hypersensitivity to durvalumab per the prescribing information; known contraindication or hypersensitivity to Fluorouracil, Leucovorin, Oxaliplatin, and Docetaxel or any of the drug excipients.
- Known history of active primary immunodeficiency (eg, HIV), other contraindications of immunotherapy or receiving immunosuppressive medication per approved label.
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- Female participants who are pregnant or breastfeeding.
- Concurrent enrollment in another clinical trial unless the study is observational, non-interventional.
- Use of any commercial ctDNA or liquid biopsy monitoring outside of the study protocol during the primary 36-month monitoring period.
- Concurrent invasive malignancy or a prior invasive malignancy whose treatment was completed within 5 years before ICF signature. Note: Participants with prior or concurrent in situ malignancies are eligible provided that adequate curative treatment is completed prior to enrollment.
- Any other concurrent severe and/or uncontrolled medical condition that would, in the Investigator's judgment, cause unacceptable safety risks, contraindicate participant participation in the clinical trial or compromise compliance with the protocol (e.g., chronic pancreatitis, chronic active hepatitis, liver cirrhosis or any other significant liver disease, active untreated or uncontrolled fungal, bacterial or viral infections, active infection requiring systemic antibacterial therapy, etc.)
Trial locations and contacts
No sites are listed yet. Contact the study team or a site near you to ask about taking part.
About this study
Official title: SIGNAL GEC-101: Signatera-Guided De-escalation of Adjuvant Therapy in Resectable Stage II-IVa Gastric/Gastric-Esophageal Cancer
The goal of this clinical trial is to assess if circulating tumor DNA, as assessed by Signatera tumor-informed MRD assay, can guide de-escalation of adjuvant therapy in patients with resectable Stage II-IVa Gastric/Gastric-Esophageal Cancer. The main question it aims to answer is:
- To demonstrate if 2-year disease-free survival (DFS) among participants with resectable clinical Stage II-IVa gastric/gastro-esophageal cancer who received neoadjuvant D-FLOT and are ctDNA negative after curative intent R0 surgery receiving adjuvant durvalumab monotherapy is non-inferior to standard of care D-FLOT.
Read more
Researchers will compare post-operative ctDNA negative participants who are receiving adjuvant durvalumab monotherapy to those who receive standard of care (D-FLOT) to see if they have similar outcomes.
Participants will be asked to:
- Receive serial ctDNA testing
- Visit their study doctor per their standard of care visits about every 3 months for first 2 years and then every 6 months for an additional 3 years
- Answer 5 questionnaires about their well-being
Read the detailed description
This is a prospective, open-label, multi-center, ctDNA-guided study with a randomized, non-inferiority component designed to examine clinical outcomes in treatment of gastric/gastric-esophageal cancer. Specifically, a component of the study will evaluate an adjuvant treatment de-escalation strategy for participants with resectable clinical Stage II-IVa gastric/gastric-esophageal cancer who have completed neoadjuvant therapy with durvalumab plus fluorouracil, leucovorin, oxaliplatin, docetaxel (D-FLOT) and R0 curative intent surgery. Concurrently, participants with post-operative ctDNA positive results will receive standard of care (SOC) D-FLOT with blinded serial ctDNA testing.
Following R0 curative intent surgery, participants will be consented for study participation. Eligible participants will undergo treatment assignment based on post-operative MRD status at 5 weeks (+/- 2 weeks), as determined by the Signatera assay.
Participants with negative post-operative circulating tumor DNA (ctDNA) results and no radiographic evidence of disease (within 6 weeks prior to randomization) will be randomized (1:1) to either SOC vs ct-DNA guided treatment. Randomized participants will be stratified according to pathologic (yp) lymph node status and tumor staging (ypT1-3, N0 vs T4 or N+), Combined Positive Score (CPS, CPS ≥ 1 vs CPS <1), and pathological complete response (yes vs no). Assigned adjuvant treatment must start no later than 12 weeks post surgery.
- Arm A (SOC Arm): Durvalumab for 1 year plus four 2 week cycles of FLOT with unblinded serial ctDNA testing and patient-reported outcomes (PROs) assessments.
- Arm B (ctDNA-guided Arm): Durvalumab monotherapy for 1 year with unblinded serial ctDNA testing and PROs assessments. Participants who become ctDNA positive up through Cycle 11 Day 1 (C11D1) will receive four 2 week cycles of FLOT added to Durvalumab.
Once adjuvant therapy is completed, all randomized participants will continue with serial ctDNA testing until recurrence and followed for up to 5 years for overall survival (OS), disease-free survival (DFS), metastasis-free survival (MFS) and disease-specific survival (DSS).
Participants with post-operative ctDNA positive results at 5 weeks (+/- 2 weeks) will not be randomized. They will continue on observation and receive SOC D-FLOT with blinded serial ctDNA testing.
- Conditions
- Gastric-Esophageal Cancer
- Being tested
- Signatera Genome ultra-sensitive ctDNA blood test
- Keywords
- ctDNA, Circulating tumor DNA, Gastric-Esophageal Cancer, Signatera, Molecular residual disease, MRD, Biomarker-guided therapy, Durvalumab, Fluorouracil, Leucovorin, Oxaliplatin, Docetaxel, D-FLOT, Adjuvant therapy, Tumor-informed assay, Gastric Cancer, Esophageal Cancer, Gastric adenocarcinoma, ctDNA-guided
- Medical subject headings
- Stomach Neoplasms, Esophageal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Signatera Genome ultra-sensitive ctDNA blood testDevice
Signatera Genome is intended for use as a post-surgical risk stratification tool for patients with resectable clinical Stage II-IVa gastric/gastro-esophageal cancer who are ctDNA negative after R0 curative intent surgery. The test is used to identify patients with no evidence of MRD following definitive surgery.
| Study group | Role | What they receive |
|---|---|---|
| ctDNA Guided (Durvalumab monotherapy for 1 year) | Experimental | Participants who become ctDNA positive up through C11D1 will receive four 2 week cycles of FLOT added to Durvalumab along with serial ctDNA testing. Receives: Device: Signatera Genome ultra-sensitive ctDNA blood test |
| SOC (Durvalumab for 1 year plus four 2 week cycles of FLOT starting C1D1) | Active comparator | Participants will receive Durvalumab for 1 year plus four 2 week cycles of FLOT starting C1D1 along with serial ctDNA testing. Receives: Device: Signatera Genome ultra-sensitive ctDNA blood test |
What is being measured
The primary outcome is the main question the study is designed to answer.
Disease Free Survival (DFS)
The primary objective of this study is to evaluate if disease free survival (DFS) among patients with resectable clinical stage II-IVa gastric/gastro-esophageal cancer who are ctDNA-negative after surgery undergoing ctDNA-guided observation is non-inferior to adjuvant D-FLOT.
Measured: 2 years from randomization to the first occurrence of disease recurrence or death from any cause, whichever occurs first
Secondary outcomes (9)
Overall Survival (OS)
Comparison of overall survival (OS) among Arm A (SOC) and Arm B (ctDNA guided) patients and assess whether adjuvant durvalumab monotherapy is non-inferior to standard of care adjuvant D-FLOT
Measured: From randomization to Year 3 and randomization to Year 5
Molecular Recurrence
Compare Arm A(SOC) relative to Arm B (ctDNA guided) time from surgery (or first ctDNA negative assessment) to the detection of ctDNA positivity by the Signatera assay.
Measured: From time of surgery up to 3 years
Metastasis-Free Survival (MFS)
To compare Arm A (SOC) relative to Arm B (ctDNA guided) on metastasis-free survival (MFS).
Measured: From randomization at Year 2, Year 3, and Year 5
Disease-Specific Survival (DFS)
To compare Arm A (SOC) relative to Arm B (ctDNA guided) on disease-specific survival (DFS).
Measured: From randomization at Year 2, Year 3, and Year 5
Discontinuation due to Adverse Events
Comparison of Arm A (SOC) relative to Arm B (ctDNA guided) on treatment discontinuation due to adverse events.
Measured: From enrollment to Year 2
Quality of Life Outcomes
Comparison of Arm A (SOC) relative to Arm B (ctDNA guided) on quality of life and disease-related symptoms using patient-reported outcomes (PROs) from European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (QLQ-C30).
Measured: From enrollment to Year 2
Quality of Life Outcomes
Comparison of Arm A (SOC) relative to Arm B (ctDNA guided) on quality of life and disease-related symptoms using patient-reported outcomes (PROs) from European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire - Stomach Cancer Module (EORTC QLQ-STO22)
Measured: From enrollment to Year 2
Quality of Life Outcomes
Comparison of Arm A (SOC) relative to Arm B (ctDNA guided) on quality of life and disease-related symptoms using patient-reported outcomes (PROs) from European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire ( EORTC-IL38).
Measured: From enrollment to Year 2
Patient Reported Treatment Tolerability
To compare Arm A (SOC) relative to Arm B (ctDNA guided) to the patient-reported tolerability of treatment using Patient Reported Outcomes of the Common Terminology Criteria for Adverse Events (PRO-CTCAE).
Measured: From enrollment to Year 2
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 May 2026
- Study startSep 2026 (estimated)
- Primary completionSep 2028 (estimated)
- Study completionSep 2034 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (24)Papers the sponsor has linked to this study.
- Other trials for Gastric-Esophageal CancerStudies of the same condition, open and under way.
- More trials run by Natera, Inc.The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 1,000 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Natera, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Adham Jurdi, MD, Study director, Natera, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07565857
- Sponsor's protocol ID
- 26-103-NCP
- Acronym
- SIGNAL GEC-101
- Status last verified
- Apr 2026
- First submitted
- 14 Apr 2026
- Last updated
- 4 May 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- No
Publications
Ychou M, Boige V, Pignon JP, Conroy T, Bouche O, Lebreton G, Ducourtieux M, Bedenne L, Fabre JM, Saint-Aubert B, Geneve J, Lasser P, Rougier P. Perioperative chemotherapy compared with surgery alone for resectable gastroesophageal adenocarcinoma: an FNCLCC and FFCD multicenter phase III trial. J Clin Oncol. 2011 May 1;29(13):1715-21. doi: 10.1200/JCO.2010.33.0597. Epub 2011 Mar 28.
PubMed 21444866Yang F, Hu Y, Shi Z, Liu M, Hu K, Ye G, Pang Q, Hou R, Tang K, Zhu Y. The occurrence and development mechanisms of esophageal stricture: state of the art review. J Transl Med. 2024 Jan 31;22(1):123. doi: 10.1186/s12967-024-04932-2.
PubMed 38297325Xu F, Feng G, Zhao H, Liu F, Xu L, Wang Q, An G. Clinicopathologic Significance and Prognostic Value of B7 Homolog 1 in Gastric Cancer: A Systematic Review and Meta-Analysis. Medicine (Baltimore). 2015 Oct;94(43):e1911. doi: 10.1097/MD.0000000000001911.
PubMed 26512615Wu P, Wu D, Li L, Chai Y, Huang J. PD-L1 and Survival in Solid Tumors: A Meta-Analysis. PLoS One. 2015 Jun 26;10(6):e0131403. doi: 10.1371/journal.pone.0131403. eCollection 2015.
PubMed 26114883Woo Y, Goldner B, Ituarte P, Lee B, Melstrom L, Son T, Noh SH, Fong Y, Hyung WJ. Lymphadenectomy with Optimum of 29 Lymph Nodes Retrieved Associated with Improved Survival in Advanced Gastric Cancer: A 25,000-Patient International Database Study. J Am Coll Surg. 2017 Apr;224(4):546-555. doi: 10.1016/j.jamcollsurg.2016.12.015. Epub 2016 Dec 23.
PubMed 28017807Thrift AP, Wenker TN, El-Serag HB. Global burden of gastric cancer: epidemiological trends, risk factors, screening and prevention. Nat Rev Clin Oncol. 2023 May;20(5):338-349. doi: 10.1038/s41571-023-00747-0. Epub 2023 Mar 23.
PubMed 36959359Siewert JR, Bottcher K, Stein HJ, Roder JD. Relevant prognostic factors in gastric cancer: ten-year results of the German Gastric Cancer Study. Ann Surg. 1998 Oct;228(4):449-61. doi: 10.1097/00000658-199810000-00002.
PubMed 9790335Smalley SR, Benedetti JK, Haller DG, Hundahl SA, Estes NC, Ajani JA, Gunderson LL, Goldman B, Martenson JA, Jessup JM, Stemmermann GN, Blanke CD, Macdonald JS. Updated analysis of SWOG-directed intergroup study 0116: a phase III trial of adjuvant radiochemotherapy versus observation after curative gastric cancer resection. J Clin Oncol. 2012 Jul 1;30(19):2327-33. doi: 10.1200/JCO.2011.36.7136. Epub 2012 May 14.
PubMed 22585691Sasako M, Sakuramoto S, Katai H, Kinoshita T, Furukawa H, Yamaguchi T, Nashimoto A, Fujii M, Nakajima T, Ohashi Y. Five-year outcomes of a randomized phase III trial comparing adjuvant chemotherapy with S-1 versus surgery alone in stage II or III gastric cancer. J Clin Oncol. 2011 Nov 20;29(33):4387-93. doi: 10.1200/JCO.2011.36.5908. Epub 2011 Oct 17.
PubMed 22010012Sasako M, Sano T, Yamamoto S, Kurokawa Y, Nashimoto A, Kurita A, Hiratsuka M, Tsujinaka T, Kinoshita T, Arai K, Yamamura Y, Okajima K; Japan Clinical Oncology Group. D2 lymphadenectomy alone or with para-aortic nodal dissection for gastric cancer. N Engl J Med. 2008 Jul 31;359(5):453-62. doi: 10.1056/NEJMoa0707035.
PubMed 18669424Obermannova RL, Leong T; ESMO Guidelines Committee. Electronic address: clinicalguidelines@esmo.org. ESMO Clinical Practice Guideline interim update on the treatment of locally advanced oesophageal and oesophagogastric junction adenocarcinoma and metastatic squamous-cell carcinoma. ESMO Open. 2025 Feb;10(2):104134. doi: 10.1016/j.esmoop.2025.104134. Epub 2025 Feb 12.
PubMed 39986705Movahed S, Norouzy A, Ghanbari-Motlagh A, Eslami S, Khadem-Rezaiyan M, Emadzadeh M, Nematy M, Ghayour-Mobarhan M, Varshoee Tabrizi F, Bozzetti F, Seilanian Toussi M. Nutritional Status in Patients with Esophageal Cancer Receiving Chemoradiation and Assessing the Efficacy of Usual Care for Nutritional Managements. Asian Pac J Cancer Prev. 2020 Aug 1;21(8):2315-2323. doi: 10.31557/APJCP.2020.21.8.2315.
PubMed 32856860Iden CR, Mustafa SM, Ogaard N, Henriksen T, Jensen SO, Ahlborn LB, Egebjerg K, Baeksgaard L, Garbyal RS, Nedergaard MK, Achiam MP, Andersen CL, Mau-Sorensen M. Circulating tumor DNA predicts recurrence and survival in patients with resectable gastric and gastroesophageal junction cancer. Gastric Cancer. 2025 Jan;28(1):83-95. doi: 10.1007/s10120-024-01556-9. Epub 2024 Oct 5.
PubMed 39369091Liu YX, Wang XS, Wang YF, Hu XC, Yan JQ, Zhang YL, Wang W, Yang RJ, Feng YY, Gao SG, Feng XS. Prognostic significance of PD-L1 expression in patients with gastric cancer in East Asia: a meta-analysis. Onco Targets Ther. 2016 May 4;9:2649-54. doi: 10.2147/OTT.S102616. eCollection 2016.
PubMed 27226727Lin JL, Lin JX, Lin GT, Huang CM, Zheng CH, Xie JW, Wang JB, Lu J, Chen QY, Li P. Global incidence and mortality trends of gastric cancer and predicted mortality of gastric cancer by 2035. BMC Public Health. 2024 Jul 2;24(1):1763. doi: 10.1186/s12889-024-19104-6.
PubMed 38956557
Study at a glance
From the registry record, last updated by the sponsor on 4 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- SIGNAL GEC-101: Signatera-Guided De-escalation of Adjuvant Therapy in Resectable Stage II-IVa Gastric/Gastric-Esophageal Cancer
- ClinicalTrials.gov ID
- NCT07565857
- Acronym / sponsor ID
- SIGNAL GEC-101 / 26-103-NCP
- Conditions
- Gastric-Esophageal Cancer
- Keywords
- ctDNA, Circulating tumor DNA, Gastric-Esophageal Cancer, Signatera, Molecular residual disease, MRD, Biomarker-guided therapy, Durvalumab
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 1,000 participants (estimated)
- Lead sponsor
- Natera, Inc.Industry (pharma, biotech, devices)
- Study start
- Sep 2026 (estimated)
- Primary completion
- Sep 2028 (estimated)
- Study completion
- Sep 2034 (estimated)
- First posted
- 4 May 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The goal of this clinical trial is to assess if circulating tumor DNA, as assessed by Signatera tumor-informed MRD assay, can guide de-escalation of adjuvant therapy in patients with resectable Stage II-IVa Gastric/Gastric-Esophageal Cancer. The main question it aims to answer is:
- To demonstrate if 2-year disease-free survival (DFS) among participants with resectable clinical Stage II-IVa gastric/gastro-esophageal cancer who received neoadjuvant D-FLOT and are ctDNA negative after curative intent R0 surgery receiving adjuvant durvalumab monotherapy is non-inferior to standard of care D-FLOT.
Researchers will compare post-operative ctDNA negative participants who are receiving adjuvant durvalumab monotherapy to those who receive standard of care (D-FLOT) to see if they have similar outcomes.
Participants will be asked to:
- Receive serial ctDNA testing
- Visit their study doctor per their standard of care visits about every 3 months for first 2 years and then every 6 months for an additional 3 years
- Answer 5 questionnaires about their well-being
Detailed description
This is a prospective, open-label, multi-center, ctDNA-guided study with a randomized, non-inferiority component designed to examine clinical outcomes in treatment of gastric/gastric-esophageal cancer. Specifically, a component of the study will evaluate an adjuvant treatment de-escalation strategy for participants with resectable clinical Stage II-IVa gastric/gastric-esophageal cancer who have completed neoadjuvant therapy with durvalumab plus fluorouracil, leucovorin, oxaliplatin, docetaxel (D-FLOT) and R0 curative intent surgery. Concurrently, participants with post-operative ctDNA positive results will receive standard of care (SOC) D-FLOT with blinded serial ctDNA testing.
Following R0 curative intent surgery, participants will be consented for study participation. Eligible participants will undergo treatment assignment based on post-operative MRD status at 5 weeks (+/- 2 weeks), as determined by the Signatera assay.
Participants with negative post-operative circulating tumor DNA (ctDNA) results and no radiographic evidence of disease (within 6 weeks prior to randomization) will be randomized (1:1) to either SOC vs ct-DNA guided treatment. Randomized participants will be stratified according to pathologic (yp) lymph node status and tumor staging (ypT1-3, N0 vs T4 or N+), Combined Positive Score (CPS, CPS ≥ 1 vs CPS <1), and pathological complete response (yes vs no). Assigned adjuvant treatment must start no later than 12 weeks post surgery.
- Arm A (SOC Arm): Durvalumab for 1 year plus four 2 week cycles of FLOT with unblinded serial ctDNA testing and patient-reported outcomes (PROs) assessments.
- Arm B (ctDNA-guided Arm): Durvalumab monotherapy for 1 year with unblinded serial ctDNA testing and PROs assessments. Participants who become ctDNA positive up through Cycle 11 Day 1 (C11D1) will receive four 2 week cycles of FLOT added to Durvalumab.
Once adjuvant therapy is completed, all randomized participants will continue with serial ctDNA testing until recurrence and followed for up to 5 years for overall survival (OS), disease-free survival (DFS), metastasis-free survival (MFS) and disease-specific survival (DSS).
Participants with post-operative ctDNA positive results at 5 weeks (+/- 2 weeks) will not be randomized. They will continue on observation and receive SOC D-FLOT with blinded serial ctDNA testing.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| ctDNA Guided (Durvalumab monotherapy for 1 year) | Experimental | Device: Signatera Genome ultra-sensitive ctDNA blood testParticipants who become ctDNA positive up through C11D1 will receive four 2 week cycles of FLOT added to Durvalumab along with serial ctDNA testing. |
| SOC (Durvalumab for 1 year plus four 2 week cycles of FLOT starting C1D1) | Active comparator | Device: Signatera Genome ultra-sensitive ctDNA blood testParticipants will receive Durvalumab for 1 year plus four 2 week cycles of FLOT starting C1D1 along with serial ctDNA testing. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- Signed and dated informed consent form (ICF) obtained prior to any trial-specific enrollment procedure.
- Age is ≥ 18 years-old at the time of ICF signature.
- Able to submit adequate archival tumor tissue (eg, 6 to 10 unstained slides at 10 microns (μm) each or 12-19 unstained slides at 5-microns (μm) plus one hematoxylin and eosin slide (see study lab manual) obtained per standard of care procedures for submission to a central laboratory for Signatera testing OR prior commercial Signatera Genome test results.
- Histologically confirmed adenocarcinoma of the stomach, esophagus and/or gastroesophageal junction (GEJ), resectable clinical Stage II-IVa per AJCC 9th edition.
- Completion of full or modified course (based on Dosing and Modification Guidelines) of neoadjuvant D-FLOT therapy (ie, two 4-week cycles of durvalumab, four 2-week cycles of FLOT) .
Key exclusion criteria (11 listed)
- Histologic presence of adenosquamous cell carcinoma, squamous cell carcinoma, gastrointestinal stromal tumor, or neuroendocrine tumors.
- Radiographic evidence of unresectable metastatic disease (ie, IVb).
- Presence of peritoneal dissemination.
- Any prior therapy (eg, radiation, chemoradiation, chemotherapy) for gastric or gastroesophageal cancer other than neoadjuvant D-FLOT and R0 curative intent surgery.
- Known contradiction or hypersensitivity to durvalumab per the prescribing information; known contraindication or hypersensitivity to Fluorouracil, Leucovorin, Oxaliplatin, and Docetaxel or any of the drug excipients.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Signatera Genome ultra-sensitive ctDNA blood testSignatera Genome is intended for use as a post-surgical risk stratification tool for patients with resectable clinical Stage II-IVa gastric/gastro-esophageal cancer who are ctDNA negative after R0 curative intent surgery. The test is used to identify patients with no evidence of MRD following definitive surgery. | Device | SOC (Durvalumab for 1 year plus four 2 week cycles of FLOT starting C1D1), ctDNA Guided (Durvalumab monotherapy for 1 year) |
Primary outcome
Disease Free Survival (DFS)
Time frame: 2 years from randomization to the first occurrence of disease recurrence or death from any cause, whichever occurs first
The primary objective of this study is to evaluate if disease free survival (DFS) among patients with resectable clinical stage II-IVa gastric/gastro-esophageal cancer who are ctDNA-negative after surgery undergoing ctDNA-guided observation is non-inferior to adjuvant D-FLOT.
9 secondary outcomes
Overall Survival (OS)
Time frame: From randomization to Year 3 and randomization to Year 5
Molecular Recurrence
Time frame: From time of surgery up to 3 years
Metastasis-Free Survival (MFS)
Time frame: From randomization at Year 2, Year 3, and Year 5
Disease-Specific Survival (DFS)
Time frame: From randomization at Year 2, Year 3, and Year 5
Discontinuation due to Adverse Events
Time frame: From enrollment to Year 2
Quality of Life Outcomes
Time frame: From enrollment to Year 2
Quality of Life Outcomes
Time frame: From enrollment to Year 2
Quality of Life Outcomes
Time frame: From enrollment to Year 2
Patient Reported Treatment Tolerability
Time frame: From enrollment to Year 2
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 May 2026.
- Background: PubMed 21444866Ychou M, Boige V, Pignon JP, Conroy T, Bouche O, Lebreton G, Ducourtieux M, Bedenne L, Fabre JM, Saint-Aubert B, Geneve J, Lasser P, Rougier P. Perioperative chemotherapy compared with surgery alone for resectable gastroesophageal adenocarcinoma: an FNCLCC and FFCD multicenter phase III trial. J Clin Oncol. 2011 May 1;29(13):1715-21. doi: 10.1200/JCO.2010.33.0597. Epub 2011 Mar 28.
- Background: PubMed 38297325Yang F, Hu Y, Shi Z, Liu M, Hu K, Ye G, Pang Q, Hou R, Tang K, Zhu Y. The occurrence and development mechanisms of esophageal stricture: state of the art review. J Transl Med. 2024 Jan 31;22(1):123. doi: 10.1186/s12967-024-04932-2.
- Background: PubMed 26512615Xu F, Feng G, Zhao H, Liu F, Xu L, Wang Q, An G. Clinicopathologic Significance and Prognostic Value of B7 Homolog 1 in Gastric Cancer: A Systematic Review and Meta-Analysis. Medicine (Baltimore). 2015 Oct;94(43):e1911. doi: 10.1097/MD.0000000000001911.
- Background: PubMed 26114883Wu P, Wu D, Li L, Chai Y, Huang J. PD-L1 and Survival in Solid Tumors: A Meta-Analysis. PLoS One. 2015 Jun 26;10(6):e0131403. doi: 10.1371/journal.pone.0131403. eCollection 2015.
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- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Adham Jurdi, MD study director
Natera, Inc.
Questions about this trial
What is this clinical trial studying?
A study testing Signatera Genome ultra-sensitive ctDNA blood test in people with Gastric-Esophageal Cancer, run by Natera, Inc..
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 15 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 4 May 2026. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact SIGNAL-GEC 101 Study Team (650-489-9050, SIGNAL-GEC101@natera.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Disease Free Survival (DFS) (time frame: 2 years from randomization to the first occurrence of disease recurrence or death from any cause, whichever occurs first). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07565857, which also lists 24 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 May 2026.