Synergistic Effects of PD-1 Antibody and Chemotherapy Followed by Surgery-centric Local Treatment in Patients with Limited-metastatic Gastric Cancer (ROSETTE)

NCT ID: NCT06468280

Last Updated: 2024-12-31

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE2

Total Enrollment

84 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-11-08

Study Completion Date

2028-12-31

Brief Summary

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ROSETTE trial is an open-label, randomized phase II study designed to investigate treatment strategies for patients with limited metastatic gastric or gastroesophageal adenocarcinoma. Eligible patients are randomized to receive either systemic treatment followed by surgeon-led local treatment, or systemic treatment alone. Systemic treatment combines immunotherapy with chemotherapy, while the surgeon-led local treatment utilizes a surgery-centric, multi-modality approach involving resection of both primary and metastatic tumors where feasible. For unresected or unresectable metastatic lesions, alternative local therapies are provided. The primary endpoint is the 1-year event-free survival (EFS) rate. Secondary endpoints include objective response rate (ORR), disease control rate (DCR), extended EFS, overall survival (OS), pathologic complete response rate (pCR), major pathologic response rate (MPR), and R0 resection rate.

Detailed Description

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Conditions

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Gastric Cancer GastroEsophageal Cancer

Keywords

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Limited metastasis Surgery Local treatment Gastric cancer Perioperative treatment

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Local Treatment Arm (Arm A)

In Phase 1, patients will receive four cycles of PD-1 antibody in combination with XELOX chemotherapy. Following this phase, a radiologic assessment will evaluate disease progression status. Patients identified as not experiencing progression will proceed with the study treatments. Subsequently, they will undergo surgeon-led local treatment, which may include standard D2 gastrectomy and metastasectomy when feasible. Non-surgical local treatments may also be administered to address unresected or unresectable metastatic lesions, either concurrently or sequentially with surgery. After surgical intervention, patients will receive up to four additional cycles of XELOX chemotherapy, followed by maintenance therapy consisting of tislelizumab and capecitabine during Phase 2 of the systemic treatment. The total treatment duration may extend up to two years from the date of enrollment.

Group Type EXPERIMENTAL

Local treatment (Surgical)

Intervention Type PROCEDURE

Radical gastrectomy with standard D2 lymphadenectomy will be performed, along with radical surgery for resectable metastatic lesions.

PD-1 Monoclonal Antibody

Intervention Type DRUG

PD-1 monoclonal antibody will be administered at a dosage of 200 mg via intravenous infusion, once every cycle, each cycle spanning three weeks. The specific PD-1 antibody used will be determined by the investigators based on clinical considerations. Potential options include Sintilimab, Toripalimab, Nivolumab, Tislelizumab, or other approved PD-1 antibody products indicated for the treatment of metastatic gastric or gastroesophageal adenocarcinoma.

XELOX Chemotherapy Regimen

Intervention Type DRUG

Oxaliplatin: 130 mg/m² administered via a 3-hour intravenous infusion on D1 of each 3-week cycle.

Capecitabine: 1000 mg/m² taken orally twice daily. The first dose is administered on the evening of D1, and the last dose on the morning of D15, consisting of 2 weeks of treatment and a 1-week break in each 3-week cycle.

Local Treatment (Non-surgical)

Intervention Type PROCEDURE

Additional local treatment for unresected metastatic lesions during phase 2 systemic therapy is permitted, including:

* Bone metastasis, distant lymph nodes, adrenal metastasis: Radiation therapy.
* Lung and liver metastasis: Radiofrequency ablation, interventional embolization, or radiation therapy.
* Peritoneal metastasis: Hyperthermic intraperitoneal chemotherapy (HIPEC).
* Other metastatic lesions: Non-surgical treatment options discussed by the multidisciplinary team.

Systemic Treatment Arm (Arm B)

In Phase 1, patients will receive four cycles of PD-1 antibody in conjunction with XELOX chemotherapy. Following this phase, a radiologic assessment will evaluate the disease progression status. Patients classified as not experiencing progression-defined as the absence of local progression, advancement of existing distant metastases, or the emergence of new distant metastatic lesions-will continue with the study treatments. In Phase 2, participants will receive an additional up to four cycles of PD-1 antibody and XELOX chemotherapy, followed by maintenance therapy consisting of PD-1 antibody and capecitabine. The total treatment duration could extend up to two years from the date of enrollment.

Group Type ACTIVE_COMPARATOR

PD-1 Monoclonal Antibody

Intervention Type DRUG

PD-1 monoclonal antibody will be administered at a dosage of 200 mg via intravenous infusion, once every cycle, each cycle spanning three weeks. The specific PD-1 antibody used will be determined by the investigators based on clinical considerations. Potential options include Sintilimab, Toripalimab, Nivolumab, Tislelizumab, or other approved PD-1 antibody products indicated for the treatment of metastatic gastric or gastroesophageal adenocarcinoma.

XELOX Chemotherapy Regimen

Intervention Type DRUG

Oxaliplatin: 130 mg/m² administered via a 3-hour intravenous infusion on D1 of each 3-week cycle.

Capecitabine: 1000 mg/m² taken orally twice daily. The first dose is administered on the evening of D1, and the last dose on the morning of D15, consisting of 2 weeks of treatment and a 1-week break in each 3-week cycle.

Interventions

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Local treatment (Surgical)

Radical gastrectomy with standard D2 lymphadenectomy will be performed, along with radical surgery for resectable metastatic lesions.

Intervention Type PROCEDURE

PD-1 Monoclonal Antibody

PD-1 monoclonal antibody will be administered at a dosage of 200 mg via intravenous infusion, once every cycle, each cycle spanning three weeks. The specific PD-1 antibody used will be determined by the investigators based on clinical considerations. Potential options include Sintilimab, Toripalimab, Nivolumab, Tislelizumab, or other approved PD-1 antibody products indicated for the treatment of metastatic gastric or gastroesophageal adenocarcinoma.

Intervention Type DRUG

XELOX Chemotherapy Regimen

Oxaliplatin: 130 mg/m² administered via a 3-hour intravenous infusion on D1 of each 3-week cycle.

Capecitabine: 1000 mg/m² taken orally twice daily. The first dose is administered on the evening of D1, and the last dose on the morning of D15, consisting of 2 weeks of treatment and a 1-week break in each 3-week cycle.

Intervention Type DRUG

Local Treatment (Non-surgical)

Additional local treatment for unresected metastatic lesions during phase 2 systemic therapy is permitted, including:

* Bone metastasis, distant lymph nodes, adrenal metastasis: Radiation therapy.
* Lung and liver metastasis: Radiofrequency ablation, interventional embolization, or radiation therapy.
* Peritoneal metastasis: Hyperthermic intraperitoneal chemotherapy (HIPEC).
* Other metastatic lesions: Non-surgical treatment options discussed by the multidisciplinary team.

Intervention Type PROCEDURE

Eligibility Criteria

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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. HER2-negative gastric cancer, confirmed by HER2 immunohistochemistry (IHC) or fluorescence in situ hybridization (FISH).
4. Gastric cancer with proficient mismatch repair (pMMR) or microsatellite stability (MSS) as determined by immunohistochemistry or NCI-recommended microsatellite markers.
5. 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) (21).

(b1) Localized peritoneal metastasis: P0CY1, P1a, or P1b, according to the Japanese Classification of Gastric Carcinoma (15th edition) (22).

(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.
6. No previous anti-tumor treatments.
7. ECOG score ≤2, no surgical contraindications.
8. Life expectancy ≥ 3 months.
9. Physical condition and organ function suitable for major abdominal surgery.
10. Willingness and ability to comply with the study protocol.
11. 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.
12. Signed informed consent with an understanding that patients can withdraw anytime.

Exclusion Criteria

1. Large Borrmann III type or Borrmann IV type, specifically ulcerative-infiltrative gastric cancer with a diameter exceeding 8 cm, or diffuse infiltrative gastric cancer(23).
2. Inability to tolerate oral chemotherapy.
3. Primary gastric lesion confined to the mucosa or submucosa with isolated ovarian metastasis.
4. Central nervous system metastasis and/or carcinomatous meningitis.
5. Allergy to any components of the study medication.
6. 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.
7. Uncontrolled pleural effusion, pericardial effusion, or ascites.
8. Weight loss ≥20% within two months before enrollment.
9. Upper gastrointestinal obstruction or physiological dysfunction.
10. Previous cytotoxic chemotherapy, radiotherapy, immunotherapy, or curative surgery.
11. Prior PD-1/PD-L1/PD-L2 or other T-cell-targeting therapy.
12. Systemic steroid or immunosuppressant use within 14 days before enrollment.
13. Live vaccine within four weeks prior to enrollment.
14. Uncontrolled systemic disease.
15. Active or past autoimmune diseases that may recur.
16. Severe chronic infections or active infections requiring systemic antibacterial, antifungal, or antiviral treatment.
17. History of lung disease.
18. Pregnancy, lactation, or planning for pregnancy.
19. HBsAg-positive with HBV DNA ≥500 IU/mL.
20. Positive HIV antibody.
21. Conditions that may impact study compliance or participation.
Minimum Eligible Age

18 Years

Maximum Eligible Age

79 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Shanghai Zhongshan Hospital

OTHER

Sponsor Role lead

Responsible Party

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Xuefei.Wang

Chief of Gastrointestinal Surgery Department

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Xuefei Wang, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Fudan University

Locations

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Zhongshan Hospital Fudan University

Shanghai, Shanghai City, China

Site Status NOT_YET_RECRUITING

Zhongshan Hospital, Fudan University

Shanghai, Shanghai Municipality, China

Site Status RECRUITING

Countries

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China

Central Contacts

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Xuefei Wang, MD, PhD

Role: CONTACT

Phone: 0

Email: [email protected]

Facility Contacts

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Xuefei Wang, MD, PhD

Role: primary

Xuefei Wang, MD, PhD

Role: backup

Xuefei Wang

Role: primary

References

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Wu YY, Lee LC, Zeng H, Gu Y, Xu C, Chen WD, Shen ZB, Shen KT, Cui YH, Sun YH, Liu TS, Tang ZQ, Wang XF. Synergistic effects of PD-1 antibody and chemotherapy 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. BMC Cancer. 2025 Jun 1;25(1):981. doi: 10.1186/s12885-025-14331-5.

Reference Type DERIVED
PMID: 40452026 (View on PubMed)

Other Identifiers

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KY2024164

Identifier Type: -

Identifier Source: org_study_id