Trial Comparing Standard of Care Therapy With and Without Sequential Cytoreductive Intervention for Patients With Metastatic Foregut Adenocarcinoma and Undetectable Circulating Tumor-Deoxyribose Nucleic Acid (ctDNA) Levels

NCT07282912 | Recruiting Phase 2 DMC FDA Device

• 1 other identifier: 2000038216
• Study Type: interventional
• Target: 54
• Locations: 1 country
• Sites: 1

Brief Summary

This is a randomized, open label, single-center, phase 2, randomized controlled trial of sequential cytoreductive intervention versus standard of care therapy for patients with intervenable oligometastatic (stage IV) cancer of the upper gastrointestinal (GI) tract and undetectable ctDNA at the time of randomization after a three-month induction chemotherapy period.

Conditions

Foregut Adenocarcinoma; Esophageal Adenocarcinoma; Gastroesophageal Adenocarcinoma; Gastric Adenocarcinoma; Pancreas Adenocarcinoma; Duodenal Adenocarcinoma; Ampullary Adenocarcinoma; Gallbladder Adenocarcinoma; Intra - and Extrahepatic Cholangiocarcinoma

Keywords

Undetectable Circulating Tumor-Deoxyribose Nucleic Acid (ctDNA) Levels; Oligometastasis; Esophageal adenocarcinoma; Gastroesophageal adenocarcinoma,; Gastric adenocarcinoma; Duodenal adenocarcinoma; Pancreatic/ampullary adenocarcinoma; Gallbladder adenocarcinoma; Intra- and extrahepatic cholangiocarcinoma.

Outcome Measures

Primary Outcomes (1)

• Number of participants with Progression Free Survival (PFS)

  PFS is defined as the time from randomization to first documented disease progression by Resist 1.1 criteria or death from any cause, whichever occurs first.

  up to 12 months post-randomization

Secondary Outcomes (4)

• Post treatment survival rate

  12 months post-randomization

• Change in European Organization for Research and Treatment of Cancer (EORTC QLQ-C30) Global Health Status score

  Post randomization at weeks 1, 3, 5, 9 and at first followup (up to 3 months)

• Change in European Organization for Research and Treatment of Cancer (EORTC QLQ-C30) Physical Functioning score

  Post randomization at weeks 1, 3, 5, 9 and at first followup (up to 3 months)

• Change in Comprehensive Score for Financial Toxicity (COST) score

  Post randomization at weeks 1, 3, 5, 9 and at first followup (up to 3 months)

Study Arms (2)

Sequential cytoreductive intervention

EXPERIMENTAL

Following the determination of undetectable levels of ctDNA, patients will undergo cytoreductive interventions for a total of three months. All sequential cytoreductive interventions must be completed within the three-month time frame following randomization. ctDNA levels will be measured.

Procedure: Sequential cytoreductive intervention; Diagnostic Test: Signatera Genome ultra-sensitive ctDNA blood test

Standard of care

ACTIVE COMPARATOR

Following the determination of undetectable levels of ctDNA, patients will continue the standard of care therapy until progression.

Diagnostic Test: Signatera Genome ultra-sensitive ctDNA blood test

Interventions

Sequential cytoreductive intervention PROCEDURE

A treatment plan that involves multiple procedures given one after another to remove cancerous tumors depending on metastasis.

Sequential cytoreductive intervention

Signatera Genome ultra-sensitive ctDNA blood test DIAGNOSTIC_TEST

A personalized blood test that detects circulating tumor DNA (ctDNA) to monitor for molecular residual disease (MRD) in patients who have been diagnosed with cancer.

Sequential cytoreductive intervention; Standard of care

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Has a primary diagnosis of AJCC 8th Edition Stage IV esophageal or gastroesophageal adenocarcinoma, gastric adenocarcinoma, pancreatic adenocarcinoma, intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma, gallbladder adenocarcinoma, duodenal, and ampullary adenocarcinoma.
• a) All participants must have confirmed histologic diagnosis of the primary tumor, which may be confirmed retrospectively by a radiologist if necessary.
• Has a primary tumor that must be locally resectable or can be treated definitively. Primary tumors included are esophageal, gastric, duodenal, ampullary, pancreatic, cholangiocarcinoma, and gall bladder carcinoma. Primary tumors should be resectable or treatable with consolidative radiotherapy or ablative therapy such as microwave ablation or trans-arterial chemo/radioembolization (cholangiocarcinomas).
• Has limited (2 sites) metastatic disease determined to be completely resectable or treatable with curative intention (see SOE) at the time of diagnosis. This includes:
• Up to five pulmonary metastases amenable to wedge resection (maximum of three wedge resections) or lobectomy (single lobectomy) or consolidative radiation/ablative therapy
• Up to five hepatic metastases amenable to hepatectomy (segmentectomy, sectionectomy, sectorectomy, minor hepatectomy, not more than three segments), wedge resection requiring a minimum of 40% of liver parenchyma following resection based on future liver remnant or a combination of partial hepatectomy and microwave ablation or trans-arterial radioembolization (TARE).
• Lymphatic metastases that are resectable or intervenable (limited to only two non-regional sites) (see Appendix 3).
• Resectable peritoneal disease with a PCI of ≤6 and the ability to obtain a CC0 cytoreduction.
• Distant metastasis must be limited to two of the above-mentioned sites (a-d).
• If both pulmonary and liver metastasis are present (a, b), then a total of five lesions will be considered oligometastatic.
• Patients with resected primary tumors can be included if they present with oligometastases at least six months after the completion of treatment of primary tumor with curative intent.
• Has adequate organ function, as described below (see Appendix 4); all screening laboratory tests should be performed within 30 days prior to the first study intervention.
• Patients must have had two concordant negative tissue informed ctDNA tests measured at different timepoints and with the second being within 45 days prior to enrollment.
• Patients must have at least 4 months of prior effective systemic therapy.
• Has hemoglobin ≥ 8 g/dL.

You may not qualify if:

• Has a positive urine pregnancy test within 3 days prior to randomization or treatment. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
• Note: In the event that 3 days have elapsed between the screening pregnancy test and the first dose of study intervention, another pregnancy test (urine or serum) must be performed and must be negative for the participant to start receiving study medication.
• Has hypoxia as defined by pulse oximeter reading \<92% at rest or requires intermittent or chronic supplemental oxygen.
• Has developed progressive disease on current line of systemic therapy.
• Has a known additional malignancy that is progressing or has required active treatment within the past three years.
• Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (e.g., breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy are not excluded.
• Has known CNS metastasis and/or carcinomatous meningitis.
• Has known osseous metastasis.
• Has clinically significant cardiac disease, including unstable angina, acute myocardial infarction within 6 months from treatment initiation, or New York Heart Association Class III or IV congestive heart failure. Medially controlled arrhythmia stable on medication is permitted.
• Has poorly controlled hypertension defined as SBP ≥150mmHg and/or DBP ≥90mmHg.
• Has moderate to severe hepatic impairment (Child-Pugh B or C).
• Has a known psychiatric or substance abuse disorder that would interfere with cooperation with the requirements of the study.
• Is unable to swallow orally administered medication or has a gastrointestinal disorder affecting absorption (severe dysphasia, bowel obstruction, malabsorption).
• Has known malignant pleural effusion or previous malignant effusion previously treated at the time of enrollment.
• Has a primary tumor that is not amenable to the treatment modalities listed in section 3.

Sponsors & Collaborators

• Yale University: lead

Study Sites (1)

Smilow Cancer Center

New Haven, Connecticut, 06519, United States

RECRUITING

MeSH Terms

Conditions

Adenocarcinoma Of Esophagus; Cholangiocarcinoma

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms

Study Officials

• Kiran Turaga, MD

  Yale University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Wumi Jemiseye, MPH

CONTACT

203-737-2073; wumi.jemiseye@yale.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 5, 2025
• First Posted: December 15, 2025
• Study Start: March 1, 2026
• Primary Completion (Estimated): June 1, 2028
• Study Completion (Estimated): June 1, 2028
• Last Updated: March 4, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)