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RECRUITINGPHASE2

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

Phase II Prospective, Open Label Randomized Controlled 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•Yale University

View on ClinicalTrials.gov

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.

Detailed Description

Patients with oligometastatic foregut (esophagus, gastric, biliary, liver and pancreatic ) cancers derive benefit from surgical resection/ablation or radiation in selected patients. ctDNA is a liquid biopsy technique that has prognostic value in identifying patients that benefit from loco regional interventions (surgery/radiation/ablation). The primary objective of this study is to assess the Progression Free Survival (PFS) of patients with the addition of sequential cytoreductive intervention versus standard of care systemic therapy in patients with metastatic foregut adenocarcinoma and undetectable ctDNA after induction chemotherapy.

Eligibility

Age

18 - 80 years

Sex

ALL

Healthy Volunteers

Inclusion Criteria

•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:
•1. Up to five pulmonary metastases amenable to wedge resection (maximum of three wedge resections) or lobectomy (single lobectomy) or consolidative radiation/ablative therapy
•2. 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).
•3. Lymphatic metastases that are resectable or intervenable (limited to only two non-regional sites) (see Appendix 3).
•4. Resectable peritoneal disease with a PCI of ≤6 and the ability to obtain a CC0 cytoreduction.
•5. Distant metastasis must be limited to two of the above-mentioned sites (a-d).
•6. If both pulmonary and liver metastasis are present (a, b), then a total of five lesions will be considered oligometastatic.
+25 more criteria

Exclusion Criteria

•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.
+4 more criteria

Locations (1)

Smilow Cancer Center

New Haven, Connecticut, United States

Key Dates

Start Date

March 1, 2026

Primary Completion Date

June 1, 2028

Completion Date

June 1, 2028

Last Updated

March 4, 2026

Enrollment

ESTIMATED participants

Conditions

Foregut AdenocarcinomaEsophageal AdenocarcinomaGastroesophageal AdenocarcinomaGastric AdenocarcinomaPancreas AdenocarcinomaDuodenal AdenocarcinomaAmpullary AdenocarcinomaGallbladder AdenocarcinomaIntra - and Extrahepatic Cholangiocarcinoma

Interventions

Sequential cytoreductive intervention

PROCEDURE

Signatera Genome ultra-sensitive ctDNA blood test

DIAGNOSTIC_TEST

Contacts

Wumi Jemiseye, MPH

CONTACT

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

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Data Source & Attribution

This clinical trial information is sourced from ClinicalTrials.gov, a service of the U.S. National Institutes of Health.

ClinicalTrials.gov last update: March 4, 2026Data synced to Clareo: March 29, 2026

Modifications: This data has been reformatted for display purposes. Eligibility criteria have been parsed into inclusion/exclusion sections. Location data has been geocoded to enable distance-based search. For the authoritative and most current information, please visit ClinicalTrials.gov.

Neither the United States Government nor Clareo Health make any warranties regarding the data. Check ClinicalTrials.gov frequently for updates.

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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

Inclusion Criteria

Exclusion Criteria

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