Foregut AdenocarcinomaPhase 2OLIGOMETSNCT07282912
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
A Phase 2 study testing Sequential cytoreductive intervention and Signatera Genome ultra-sensitive ctDNA blood test in people with Foregut Adenocarcinoma and Esophageal Adenocarcinoma, run by Yale University at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Foregut Adenocarcinoma, Esophageal Adenocarcinoma, Gastroesophageal Adenocarcinoma
- What is being tested?
- Sequential cytoreductive intervention and Signatera Genome ultra-sensitive ctDNA blood test
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 54 participants
- Where
- 1 siteUnited States
- Study dates
- 2 Jun 2026to Jun 2028
- Phase
- Phase 2
- 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 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
- 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).
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- 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.
- Has ANC ≥ 1500/uL.
- Has platelet count ≥ 75000/uL.
- Has total bilirubin ≤ 1.5 times the upper limit of normal (ULN).
- Has aspartate aminotransferase (AST) \& alanine aminotransferase (ALT) ≤ 5 times ULN.
- Has creatinine clearance ≥ 50 mL/min.
- Patient who is at least 18 years of age at the time of signing informed consent and less than 81 years of age at the time of signing informed consent.
- Has an ECOG performance status score 0-1 (see Appendix 6) at the time of randomization.
- A male participant must agree to use contraception (barrier birth control, abstinence) during the treatment period and for at least 95 days following completion, corresponding to time needed to eliminate any study intervention(s), and refrain from donating sperm during this period.
- A female participant of childbearing age is eligible to participate if she is not pregnant, not breastfeeding, and agrees to use contraception (hormonal, barrier birth control, or abstinence) during the treatment period and for at least 95 days following completion. Should a woman become pregnant or suspect that she is pregnant while participating in this study, she should inform her treating physician immediately.
- Informed Consent
- The participant (or legally acceptable representative if applicable) provides written informed consent for the study. The participant may also provide consent for the Foundation for Blood Research (FBR). However, the participant may participate in the main study without participating in the FBR.
Who cannot join
- 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.
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- 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 histologic subtypes not included in the inclusion criteria (including esophageal squamous cell carcinoma, gastroenteropancreatic neuroendocrine tumors, hepatocellular carcinoma, etc.).
- Has a primary tumor that is not amenable to the treatment modalities listed in section 3.
- Has albumin level less than 3.0 g/dL despite appropriate nutritional support. Diagnostic Assessments
- Has detectable ctDNA at the time of enrollment.
- Has an active infection requiring systemic therapy.
- Has known active TB/COVID infection.
- Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (dosing exceeding 10mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of the study intervention.
- Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 95 days after the last study intervention.
- Inability to receive chemotherapy and/or surgery and/or radiotherapy and/or ablative procedures due to medical/insurance reasons.
- Requires emergency surgery due to bleeding, perforation, or obstruction.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Smilow Cancer Center
New Haven, Connecticut, 06519
About this study
Official title: 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
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.
Read the 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.
- Conditions
- Foregut Adenocarcinoma, Esophageal Adenocarcinoma, Gastroesophageal Adenocarcinoma, Gastric Adenocarcinoma, Pancreas Adenocarcinoma, Duodenal Adenocarcinoma
- Being tested
- Sequential cytoreductive intervention, Signatera Genome ultra-sensitive ctDNA blood test
- 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.
- Medical subject headings
- Adenocarcinoma Of Esophagus, Cholangiocarcinoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Sequential cytoreductive interventionProcedure or surgery
A treatment plan that involves multiple procedures given one after another to remove cancerous tumors depending on metastasis.
Signatera Genome ultra-sensitive ctDNA blood testDiagnostic 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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Diagnostic Test: Signatera Genome ultra-sensitive ctDNA blood test |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: up to 12 months post-randomization
Secondary outcomes (4)
Post treatment survival rate
One year post treatment survival rate: Defined as the number of participants alive at one year after intervention.
Measured: 12 months post-randomization
Change in European Organization for Research and Treatment of Cancer (EORTC QLQ-C30) Global Health Status score
EORTC QLQ-C30 is a questionnaire with a global health status/QoL scale that uses a 7-point scale scoring with anchors (1=very poor and 7=excellent). Score range: 0 to 100.Higher score: Indicates a better global health status and quality of life.
Measured: 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
EORTC QLQ-C30 is a questionnaire with a physical functioning scale. Score range: 0 to 100.Higher score: Indicates a better global health status and quality of life.
Measured: 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
A lower COST score indicates higher financial toxicity, with the total score ranging from 0 to 44,
Measured: Post randomization at weeks 1, 3, 5, 9 and at first followup (up to 3 months)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Dec 2025
- Study start2 Jun 2026
- Primary completionJun 2028 (estimated)
- Study completionJun 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Foregut AdenocarcinomaStudies of the same condition, open and under way.
- More trials run by Yale UniversityThe 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 54 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Yale University
- Sponsor type
- University, hospital or other
- Collaborators
- Gastro-Intestinal Research Foundation
- Responsible party
- Sponsor
- Investigators
- Kiran Turaga, MD, Principal investigator, Yale University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07282912
- Sponsor's protocol ID
- 2000038216
- Acronym
- OLIGOMETS
- Status last verified
- Sep 2026
- First submitted
- 5 Dec 2025
- Last updated
- 8 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 8 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT07282912
- Acronym / sponsor ID
- OLIGOMETS / 2000038216
- Conditions
- Foregut Adenocarcinoma, Esophageal Adenocarcinoma, Gastroesophageal Adenocarcinoma, Gastric Adenocarcinoma, Pancreas Adenocarcinoma, Duodenal Adenocarcinoma
- Keywords
- Undetectable Circulating Tumor-Deoxyribose Nucleic Acid (ctDNA) Levels, Oligometastasis, Esophageal adenocarcinoma, Gastroesophageal adenocarcinoma,, Gastric adenocarcinoma, Duodenal adenocarcinoma, Pancreatic/ampullary adenocarcinoma, Gallbladder adenocarcinoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 54 participants (estimated)
- Lead sponsor
- Yale UniversityUniversity, hospital or other
- Collaborators
- Gastro-Intestinal Research Foundation
- Study start
- 2 Jun 2026 (actual)
- Primary completion
- Jun 2028 (estimated)
- Study completion
- Jun 2028 (estimated)
- First posted
- 15 Dec 2025 (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.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Sequential cytoreductive intervention | Experimental | Procedure: Sequential cytoreductive intervention, Diagnostic Test: Signatera Genome ultra-sensitive ctDNA blood testFollowing 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. |
| Standard of care | Active comparator | Diagnostic Test: Signatera Genome ultra-sensitive ctDNA blood testFollowing the determination of undetectable levels of ctDNA, patients will continue the standard of care therapy until progression. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (26 listed)
- 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.
- 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:
- 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.
Key exclusion criteria (24 listed)
- 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.
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 |
|---|---|---|
| Sequential cytoreductive interventionA treatment plan that involves multiple procedures given one after another to remove cancerous tumors depending on metastasis. | Procedure or surgery | Sequential cytoreductive intervention |
| Signatera Genome ultra-sensitive ctDNA blood testA personalized blood test that detects circulating tumor DNA (ctDNA) to monitor for molecular residual disease (MRD) in patients who have been diagnosed with cancer. | Diagnostic test | Sequential cytoreductive intervention, Standard of care |
Primary outcome
Number of participants with Progression Free Survival (PFS)
Time frame: up to 12 months post-randomization
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.
4 secondary outcomes
Post treatment survival rate
Time frame: 12 months post-randomization
Change in European Organization for Research and Treatment of Cancer (EORTC QLQ-C30) Global Health Status score
Time frame: 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
Time frame: 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
Time frame: Post randomization at weeks 1, 3, 5, 9 and at first followup (up to 3 months)
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 8 Sep 2026.
- Individual participant dataSharing planned: No
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.
Kiran Turaga, MD principal investigator
Yale University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Sequential cytoreductive intervention and Signatera Genome ultra-sensitive ctDNA blood test in people with Foregut Adenocarcinoma and Esophageal Adenocarcinoma, run by Yale University at 1 site in United States.
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 26 inclusion and 24 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: looking for participants now, as of the sponsor's last update on 8 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
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.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
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 Wumi Jemiseye, MPH (203-737-4475, wumi.jemiseye@yale.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of participants with Progression Free Survival (PFS) (time frame: up to 12 months post-randomization). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 8 Sep 2026.