Trial Title:
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
Condition:
Gastric Cancer
GastroEsophageal Cancer
Conditions: Official terms:
Stomach Neoplasms
Antibodies
Antibodies, Monoclonal
Conditions: Keywords:
Limited metastasis
Surgery
Local treatment
Gastric cancer
Perioperative treatment
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Not yet recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Procedure
Intervention name:
Radical surgery
Description:
Radical gastrectomy with standard D2 lymphadenectomy will be performed, along with
radical surgery for resectable metastatic lesions.
Arm group label:
Local Treatment Arm (Arm A)
Intervention type:
Drug
Intervention name:
PD-1 Monoclonal Antibody
Description:
PD-1 monoclonal antibody will be administered at a dosage of 20 mg/kg via intravenous
infusion, once every cycle, each cycle spanning three weeks. The investigators will
select the specific PD-1 antibody utilized based on clinical considerations, which may
include sintilimab, toripalimab, or nivolumab.
Arm group label:
Local Treatment Arm (Arm A)
Arm group label:
Systemic Treatment Arm (Arm B)
Intervention type:
Drug
Intervention name:
XELOX Chemotherapy Regimen
Description:
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.
Arm group label:
Local Treatment Arm (Arm A)
Arm group label:
Systemic Treatment Arm (Arm B)
Intervention type:
Procedure
Intervention name:
Local Treatment
Description:
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.
Arm group label:
Local Treatment Arm (Arm A)
Summary:
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.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Men or women aged 18-75.
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-1, HIV-2, HTLV-1 antibodies, or HCV RNA.
21. Conditions that may impact study compliance or participation.
Gender:
All
Minimum age:
18 Years
Maximum age:
75 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Zhongshan Hospital Fudan University
Address:
City:
Shanghai
Zip:
200032
Country:
China
Contact:
Last name:
Xuefei Wang, MD, PhD
Phone:
0
Email:
wang.xuefei@zs-hospital.sh.cn
Contact backup:
Last name:
Xuefei Wang, MD, PhD
Start date:
November 2024
Completion date:
December 2028
Lead sponsor:
Agency:
Shanghai Zhongshan Hospital
Agency class:
Other
Source:
Shanghai Zhongshan Hospital
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06468280
