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Immune Checkpoint TherapyPhase 2NCT06980389

Node-Sparing Short-Course Radiotherapy Plus First-Line Therapy and PD-1 Inhibitor in Unresectable/Metastastic pMMR/MSS Gastric Cancer (MODIFI-GC)

A Phase 2 study testing Node-Sparing Radiotherapy plus first-line therapy and First-line treatment in people with Immune Checkpoint Therapy and Radiotherapy, run by Sixth Affiliated Hospital, Sun Yat-sen University at 1 site in China.

Not yet recruiting

Opening soon. The study is approved but enrolment has not started yet. Sites may already take enquiries.

Sites and contacts
Official record
Search all trials

Trial summary

For patients with unresectable locally advanced or metastatic gastric cancer, systemic anti-tumor therapy remains the mainstay of treatment. Combining chemotherapy with immune checkpoint inhibitors has gradually become the standard first-line treatment for advanced gastric cancer. Read more about this study

Who is it for?
Ages 18 to 75 years
What is being tested?
Node-Sparing Radiotherapy plus first-line therapy and First-line treatment
Could I receive a placebo?
No, everyone receives an active treatment
How many people
176 participants
Where
1 siteChina
Study dates
31 May 2025to 31 Dec 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 75 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Voluntarily signs a written informed consent form.
  • Aged between 18 and 75 years at the time of enrollment.
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
  • Expected survival of more than 3 months.
  • At least one measurable lesion as defined by RECIST 1.1.
  • Histologically confirmed unresectable locally advanced or metastatic adenocarcinoma of the stomach or gastroesophageal junction.
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  • Tumor biopsy indicates proficient mismatch repair (pMMR) based on positive immunohistochemical staining for MSH1, MSH2, MSH6, and PMS2, or microsatellite stability (MSS) by genetic testing.
  • No prior systemic anti-tumor therapy before study treatment, including radiotherapy, chemotherapy, immunotherapy, biologics, or small-molecule targeted therapy.
  • Agrees to provide tumor tissue and peripheral blood samples during screening and throughout the study for research purposes.
  • Adequate organ function as defined below:
  • Hematologic (without blood transfusion or hematopoietic growth factor support within 7 days prior to treatment):
  • Absolute neutrophil count (ANC) ≥ 1.5 × 10⁹/L
  • Platelet count ≥ 100 × 10⁹/L
  • Hemoglobin ≥ 90 g/L
  • Renal:
  • Calculated creatinine clearance (CrCl) ≥ 50 mL/min using the Cockcroft-Gault formula:
  • CrCl = [(140 - age) × weight (kg) × 0.85 (if female)] / [72 × serum creatinine (mg/dL)]
  • Urine protein < 2+ by dipstick or < 1.0 g/24 h
  • Hepatic:
  • Total bilirubin (TBil) ≤ 1.5 × upper limit of normal (ULN)
  • AST and ALT ≤ 2.5 × ULN
  • Serum albumin ≥ 28 g/L
  • Coagulation:
  • INR and APTT ≤ 1.5 × ULN
  • Cardiac:
  • Left ventricular ejection fraction (LVEF) ≥ 50%
  • Women of childbearing potential must have a negative urine or serum pregnancy test within 3 days prior to study treatment. If urine test is inconclusive, a serum test result shall prevail. Women of childbearing potential who are sexually active with non-sterilized male partners must agree to use an acceptable method of contraception from screening through 120 days after the last dose of study drug. Whether to discontinue contraception after this period should be discussed with the investigator. Periodic abstinence and calendar methods are not acceptable.
  • Women of childbearing potential are defined as those who have not undergone surgical sterilization (bilateral tubal ligation, bilateral oophorectomy, or hysterectomy) and who are not postmenopausal (defined as ≥12 months of amenorrhea without alternative medical cause and with serum FSH levels in the postmenopausal range).
  • Highly effective contraception methods are those with a failure rate <1% per year when used consistently and correctly. In addition to barrier methods, hormonal contraception (e.g., oral contraceptives) must also be used.
  • Willing and able to comply with all scheduled visits, treatment plans, laboratory tests, and other study requirements.

Who cannot join

  • • Radiotherapy within 4 weeks prior to enrollment or radionuclide therapy within 8 weeks, except for palliative radiotherapy to bone metastases.
  • History of other malignancies within 5 years prior to enrollment, except for those considered cured by local therapy, such as basal cell carcinoma, squamous cell carcinoma of the skin, superficial bladder cancer, or ductal carcinoma in situ of the breast.
  • Gastrointestinal perforation and/or fistula within 6 months prior to enrollment.
  • Clinically significant bowel obstruction.
  • Symptomatic central nervous system (CNS) metastases.
  • Diagnosis of HER2-positive gastric or gastroesophageal junction adenocarcinoma.
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  • Inability to swallow oral medications, malabsorption syndrome, or any other condition affecting gastrointestinal absorption.
  • Prior systemic or local anti-tumor therapy for gastric cancer, including curative surgery, chemotherapy, radiotherapy, immunotherapy (e.g., immune checkpoint inhibitors, agonists, or cell therapy), biologics, or small-molecule targeted agents.
  • Receipt of nonspecific immunomodulatory agents (e.g., interleukins, interferons, thymic peptides, tumor necrosis factor) within 2 weeks prior to study treatment (excluding IL-11 for thrombocytopenia); use of anti-tumor traditional Chinese medicine within 1 week prior to study treatment.
  • Active autoimmune disease requiring systemic therapy within the past 2 years (e.g., corticosteroids, immunosuppressants, DMARDs). Replacement therapy (e.g., thyroid hormone, insulin, or physiologic corticosteroids for adrenal/pituitary insufficiency) is permitted.
  • History of or current interstitial lung disease or non-infectious pneumonitis requiring systemic corticosteroids.
  • History of significant bleeding disorders or coagulopathy; current or prior long-term anticoagulation (e.g., atrial fibrillation with CHADS2 score ≥ 2).
  • Uncontrolled comorbidities including, but not limited to, decompensated cirrhosis, nephrotic syndrome, uncontrolled metabolic disorders, severe active peptic ulcer or gastritis, or psychiatric/social conditions interfering with protocol compliance or informed consent.
  • History of myocarditis, cardiomyopathy, or malignant arrhythmia; unstable angina, heart failure requiring hospitalization, or vascular disease (e.g., aortic aneurysm requiring repair or DVT) within 12 months before treatment; other cardiac conditions that may interfere with safety evaluation, such as poorly controlled arrhythmias, myocardial infarction, or ischemia.
  • Within 6 months prior to treatment: gastroesophageal varices, severe ulcers, unhealed wounds, GI perforation, fistula, intestinal obstruction, intra-abdominal abscess, or acute GI bleeding.
  • Arterial thromboembolism, grade ≥3 venous thromboembolism (per NCI CTCAE v5.0), TIA, stroke, hypertensive crisis, or hypertensive encephalopathy within 6 months before treatment.
  • Acute exacerbation of COPD within 1 month prior to treatment; uncontrolled hypertension (SBP ≥ 160 mmHg or DBP ≥ 100 mmHg despite oral therapy).
  • Active or prior history of inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis) or chronic diarrhea.
  • Serious infection within 4 weeks prior to treatment, including those requiring hospitalization, sepsis, or severe pneumonia; active systemic infection requiring anti-infective therapy within 10 days before treatment (excluding antiviral therapy for HBV or HCV).
  • Major surgery or significant trauma within 30 days prior to treatment; minor local surgery within 3 days prior (excluding central venous catheter placement via peripheral vein).
  • History of immunodeficiency; HIV antibody positive; long-term use of systemic corticosteroids or immunosuppressants.
  • Known active tuberculosis (TB), or suspected active TB not ruled out by clinical assessment (e.g., sputum testing, chest imaging); known active syphilis.
  • History of allogeneic organ or hematopoietic stem cell transplantation.
  • Untreated active hepatitis B infection (HBsAg positive and HBV DNA > 1,000 copies/mL or 200 IU/mL); patients with HBV must receive antiviral therapy during the study. Active hepatitis C infection (HCV antibody positive with detectable HCV RNA) is also excluded.
  • Receipt of a live vaccine within 30 days prior to treatment or planned during the study period.
  • Known allergy to any component of study drugs or history of severe hypersensitivity to monoclonal antibodies.
  • Known history of psychiatric disorders, substance abuse, alcoholism, or drug addiction.
  • Pregnant or breastfeeding women.
  • Any condition, treatment, or abnormal laboratory findings that may confound study results, interfere with study participation, or not be in the best interest of the participant.
  • Local or systemic disease caused by benign tumors, or tumor-related complications with high medical risk or uncertain prognosis (e.g., leukemoid reaction with WBC > 20 × 10⁹/L, cachexia with >10% weight loss in 3 months before screening, or BMI ≤ 18).

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Yanxin Luo, M.D., Ph.D. contact

+86-20-38254221

luoyx25@mail.sysu.edu.cn

China1 site

  • The Sixth Affiliated Hospital of Sun Yat-sen University

    Guangzhou, Guangdong, 510655

Other trials in China

About this study

Official title: Node-Sparing Short-Course Radiotherapy Followed by First-Line Therapy Plus PD-1 Inhibitor in Unresectable Locally Advanced or Metastatic pMMR/MSS Gastric Cancer: A Prospective, Randomized, Controlled Phase II Trial (MODIFI-GC)

For patients with unresectable locally advanced or metastatic gastric cancer, systemic anti-tumor therapy remains the mainstay of treatment. Combining chemotherapy with immune checkpoint inhibitors has gradually become the standard first-line treatment for advanced gastric cancer. Radiotherapy can enhance the release of tumor-associated antigens, thereby improving the responsiveness of MSS/pMMR tumors to PD-1 inhibitors. Tumor-draining lymph nodes (TDLNs) are key sites for the anti-tumor activity of PD-1 blockade; however, radiation-induced damage and fibrosis may impair lymphatic drainage and local immune responses. Previous studies have suggested that irradiation of the primary tumor combined with immune checkpoint blockade can produce an abscopal effect, mediating regression of distant metastases. This study aims to evaluate whether node-sparing modified short-course radiotherapy followed by chemotherapy and PD-1 blockade can improve 2-year progression-free survival (PFS) in patients with unresectable locally advanced or metastatic gastric or gastroesophageal junction adenocarcinoma.

Being tested
Node-Sparing Radiotherapy plus first-line therapy, First-line treatment
Medical subject headings
Stomach Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Node-Sparing Radiotherapy plus first-line therapyCombination product

    Patients will receive node-sparing modified short-course radiotherapy, followed by standard first-line chemotherapy combined with a PD-1 inhibitor starting 2-5 days after radiotherapy. Treatment will continue until disease progression or the occurrence of unacceptable toxicity.

  • First-line treatmentCombination product

    Patients will receive standard first-line chemotherapy combined with a PD-1 inhibitor. Treatment will continue until disease progression or the occurrence of unacceptable toxicity.

Study groups in NCT06980389
Study groupRoleWhat they receive
Node-sparing Radiotherapy GroupExperimentalNot described
Receives: Combination Product: Node-Sparing Radiotherapy plus first-line therapy
First-line therapy GroupActive comparatorNot described
Receives: Combination Product: First-line treatment

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Progression-free survival (PFS)

    Measured: From initiation of treatment until disease progression or death, whichever occurs first, assessed over a period of up to 24 months

Secondary outcomes (8)

  1. Objective response rate

    Measured: From the start of treatment until disease progression, assessed over a period of up to 24 months

  2. Duration of response

    Measured: From the first documented occurrence of complete response (CR) or partial response (PR) to the first documented disease progression (per RECIST v1.1) or death from any cause, whichever occurs first, assessed over a period of up to 24 months

  3. Disease control rate

    Measured: From treatment start to the end of study at 2 years

  4. Overall survival (OS) rate

    Measured: From treatment start to the end of study at 2 years

  5. Treatment related adverse effect

    Measured: From treatment start to 30 days after the end of treatment

  6. R0 resection rate

    Measured: From treatment start to the end of study at 2 years

  7. Quality of life by EORTC QLQ-C30

    Measured: From treatment start to the end of study at 2 years

  8. EORTC QLQ-STO22

    Measured: From treatment start to the end of study at 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted20 May 2025
  2. Study start31 May 2025 (estimated)
  3. Primary completion31 Dec 2027 (estimated)
  4. Study completion31 Dec 2028 (estimated)

Resources

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
176 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06980389
Sponsor's protocol ID
2025ZSLYEC-226
Status last verified
May 2025
First submitted
24 Apr 2025
Last updated
20 May 2025
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Node-Sparing Radiotherapy plus first-line therapy and First-line treatment in people with Immune Checkpoint Therapy and Radiotherapy, run by Sixth Affiliated Hospital, Sun Yat-sen University at 1 site in China.

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 30 inclusion and 30 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: opening soon, as of the sponsor's last update on 20 May 2025. 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 China. 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 Yanxin Luo, M.D., Ph.D. (+86-20-38254221, luoyx25@mail.sysu.edu.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Progression-free survival (PFS) (time frame: From initiation of treatment until disease progression or death, whichever occurs first, assessed over a period of up to 24 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06980389.

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 20 May 2025.

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