Signatera-Guided De-escalation of Adjuvant Therapy in Resectable Stage II-IVa Gastric/Gastric-Esophageal Cancer
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
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.
official title
SIGNAL GEC-101: Signatera-Guided De-escalation of Adjuvant Therapy in Resectable Stage II-IVa Gastric/Gastric-Esophageal Cancer