Combining PD-1 antibody and chemotherapy followed by surgery for limited metastatic gastric cancer

Synergistic Effects of PD-1 Antibody and Chemotherapy/Targeted Therapy Followed by Surgery-centric Local Treatment in Patients With Limited-metastatic Gastric or Gastroesophageal Adenocarcinoma (ROSETTE Trial): an Open-label, Single-center, Randomized Phase 2 Trial

This study tests if combining immunotherapy and chemotherapy with surgery can help people with limited metastatic gastric cancer live longer and feel better compared to just using the treatments without surgery.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 84 (estimated)
• Ages: 18 Years to 79 Years
• Sex: All
• Sponsor: Shanghai Zhongshan Hospital (Academic / other)
• Drugs / interventions: chemotherapy, immunotherapy, radiation
• Locations: 2 sites (Shanghai, Shanghai City and 1 other locations)
• Trial ID: NCT06468280 on ClinicalTrials.gov

What this trial studies

The ROSETTE trial is an open-label, randomized phase II study aimed at evaluating treatment strategies for patients with limited metastatic gastric or gastroesophageal adenocarcinoma. Participants will be assigned to receive either a combination of systemic treatment, which includes immunotherapy and chemotherapy, followed by local surgical treatment, or systemic treatment alone. The study focuses on the effectiveness of a surgery-centric approach to manage both primary and metastatic tumors, with the primary goal of assessing the 1-year event-free survival rate. Secondary outcomes will include various measures of treatment response and survival.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18-79 with pathologically confirmed HER2-negative gastric or gastroesophageal junction adenocarcinoma and limited metastases.

Not a fit: Patients with unresectable primary tumors or those with HER2-positive gastric cancer may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could significantly improve survival rates and treatment outcomes for patients with limited metastatic gastric cancer.

How similar studies have performed: Other studies have shown promising results with similar combinations of immunotherapy and chemotherapy in treating gastric cancer, indicating potential for success in this approach.

Eligibility criteria

Inclusion Criteria:

1. Men or women aged 18-79.
2. Pathologically confirmed gastric adenocarcinoma or gastroesophageal junction adenocarcinoma (Siewert II or III only) with known PD-L1 expression status.
3. Gastric cancer with proficient mismatch repair (pMMR) or microsatellite stability (MSS) as determined by immunohistochemistry or NCI-recommended microsatellite markers.
4. Primary gastric cancer lesions are resectable, with limited distant metastases meeting the either of the following criteria: (1) condition (a) only; (2) any single condition from (b), with or without (a).

   (a) Non-regional intra-abdominal lymph node metastasis: Include metastasis to the superior mesenteric artery, middle colic artery, and para-aortic/retroperitoneal nodes (according to AJCC 8th edition standards).

   (b1) Localized peritoneal metastasis: P0CY1, P1a, or P1b, according to the Japanese Classification of Gastric Carcinoma (15th edition).

   (b2) Liver metastasis: Up to 5 metastatic lesions. (b3) Lung metastasis: Up to 5 unilateral metastatic lesions. (b4) Ovarian metastasis: Unilateral or bilateral. (b5) Adrenal metastasis: Unilateral or bilateral. (b6) Single-region extra-abdominal lymph node metastasis: Such as cervical, supraclavicular, or mediastinal lymph nodes.

   (b7) Bone metastasis limited to a single radiation field. (b8) Other limited metastases as determined by the research team.
5. No previous anti-tumor treatments.
6. ECOG score ≤2, no surgical contraindications.
7. Life expectancy ≥ 3 months.
8. Physical condition and organ function suitable for major abdominal surgery.
9. Willingness and ability to comply with the study protocol.
10. Fertile women with a negative urine or serum pregnancy test and agreement to use effective contraception during the study and for 180 days after the last dose. Non-sterilized men must also agree to use effective contraception.
11. Signed informed consent with an understanding that patients can withdraw anytime.

Exclusion Criteria:

1. Inability to tolerate oral chemotherapy.
2. Primary gastric lesion confined to the mucosa or submucosa with isolated ovarian metastasis.
3. Central nervous system metastasis and/or carcinomatous meningitis.
4. Allergy to any components of the study medication.
5. History of previous malignancies or concurrent other malignancies, with the exception of completely resected basal cell or squamous cell skin cancer, superficial bladder cancer, carcinoma in situ of the cervix or breast, and other tumors with no recurrence for at least 5 years.
6. Uncontrolled pleural effusion, pericardial effusion, or ascites.
7. Weight loss ≥20% within two months before enrollment.
8. Upper gastrointestinal obstruction or physiological dysfunction.
9. Previous cytotoxic chemotherapy, radiotherapy, immunotherapy, or curative surgery.
10. Prior PD-1/PD-L1/PD-L2 or other T-cell-targeting therapy.
11. Systemic steroid or immunosuppressant use within 14 days before enrollment.
12. Live vaccine within four weeks prior to enrollment.
13. Uncontrolled systemic disease.
14. Active or past autoimmune diseases that may recur.
15. Severe chronic infections or active infections requiring systemic antibacterial, antifungal, or antiviral treatment.
16. History of lung disease.
17. Pregnancy, lactation, or planning for pregnancy.
18. HBsAg-positive with HBV DNA ≥500 IU/mL.
19. Positive HIV antibody.
20. Conditions that may impact study compliance or participation.

Where this trial is running

Shanghai, Shanghai City and 1 other locations

• Zhongshan Hospital Fudan University — Shanghai, Shanghai City, China (Not_yet_recruiting)
• Zhongshan Hospital, Fudan University — Shanghai, Shanghai Municipality, China (Recruiting)

Study contacts

• Principal investigator: Xuefei Wang, MD, PhD — Fudan University
• Study coordinator: Xuefei Wang, MD, PhD

Conditions Gastric Cancer; GastroEsophageal Cancer; Limited metastasis; Surgery; Local treatment; Gastric cancer; Perioperative treatment