Signatera-Guided De-escalation of Adjuvant Therapy in Resectable Stage II-IVa Gastric/Gastric-Esophageal Cancer

NCT07565857 | Not Yet Recruiting FDA Device

• 1 other identifier: 26-103-NCP
• Study Type: interventional
• Target: 1,000
• Locations: 0 countries
• Sites: N/A

Brief 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. 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

Conditions

Gastric-Esophageal Cancer

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

Outcome Measures

Primary Outcomes (1)

• 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.

  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)

  From randomization to Year 3 and randomization to Year 5

• Molecular Recurrence

  From time of surgery up to 3 years

• Metastasis-Free Survival (MFS)

  From randomization at Year 2, Year 3, and Year 5

• Disease-Specific Survival (DFS)

  From randomization at Year 2, Year 3, and Year 5

• Discontinuation due to Adverse Events

  From enrollment to Year 2

Other Outcomes (2)

• Assess ctDNA Clearance Arm B (ctDNA Guided)

  From randomization to 2 years, 3 years, and 5 years

• Assess ctDNA Clearance in Arm A (SOC)

  From randomization to 2 years, 3 years, and 5 years

Study Arms (2)

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.

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.

Device: Signatera Genome ultra-sensitive ctDNA blood test

Interventions

Signatera Genome ultra-sensitive ctDNA blood test DEVICE

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.

SOC (Durvalumab for 1 year plus four 2 week cycles of FLOT starting C1D1); ctDNA Guided (Durvalumab monotherapy for 1 year)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).
• 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.

You may not qualify if:

• 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.
• 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.)

Sponsors & Collaborators

• Natera, Inc.: lead

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MeSH Terms

Conditions

Stomach Neoplasms; Esophageal Neoplasms

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases; Head and Neck Neoplasms; Esophageal Diseases

Study Officials

• Adham Jurdi, MD

  Natera, Inc.

  STUDY DIRECTOR

Central Study Contacts

SIGNAL-GEC 101 Study Team

CONTACT

650-489-9050; SIGNAL-GEC101@natera.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 14, 2026
• First Posted: May 4, 2026
• Study Start (Estimated): September 1, 2026
• Primary Completion (Estimated): September 1, 2028
• Study Completion (Estimated): September 1, 2034
• Last Updated: May 4, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share