Radiotherapy, Chemotherapy and Anti-PD-1 Immunotherapy Followed by Surgical Resection in Patients With Limited Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma: A Prospective, Single Arm, Phase II Trial
Overview
- Phase
- Phase 2
- Intervention
- Radiotherapy targeted to the primary lesion
- Conditions
- Adenocarcinoma
- Sponsor
- Fudan University
- Enrollment
- 55
- Locations
- 1
- Primary Endpoint
- Overall survival (OS)
- Status
- Recruiting
- Last Updated
- 2 years ago
Overview
Brief Summary
The goal of this clinical trial is to evaluate the efficacy and safety of radiotherapy combined with chemotherapy and anti-PD-1 immunotherapy followed by surgery for the primary and metastatic lesions in patients with limited metastatic gastric or gastroesophageal junction adenocarcinoma. The main questions it aims to answer are: 1) If the multimodal treatment which includes anti-PD-1 immunotherapy and local therapies will improve the survival of this group of patients. 2) If the multimodal treatment which includes anti-PD-1 immunotherapy and local therapies can be performed safely in this group of patients.
Participants will receive short course hypofractionated radiotherapy (HFRT) for the primary lesion, HFRT or stereotactic body radiotherapy (SBRT) for metastatic lesions, combined with systemic chemotherapy and anti-PD-1 immunotherapy. For patients with HER2-positive cancer (defined as IHC 3+ or 2+/ISH+), trastuzumab is used along with chemotherapy and anti-PD-1 antibody. Then, surgical resections of primary and metastatic lesions are performed as much as possible. For patients who need a widely invasive surgical approach or are inoperable, local ablative therapies such as radiofrequency ablation (RFA) and microwave ablation (MVA) can be alternatives. For patients undergoing surgical resections, postoperative treatment includes chemotherapy, which is determined by the researcher, and PD-1 antibody, which will be maintained until one year after surgery.
Investigators
Dazhi Xu
Professor, Chief Physician, Head of the First Department of Gastric Surgery, Fudan University Shanghai Cancer Center
Fudan University
Eligibility Criteria
Inclusion Criteria
- •Histopathologically confirmed adenocarcinoma of stomach (G) or gastroesophageal junction (GEJ) (excluding Siewert type I).
- •Limited metastatic status of disease.
- •At least one evaluable lesion in CT/MRI according to RESIST 1.1 is required.
- •The status of HER2 is clear.
- •pMMR/MSS confirmed by immunohistochemistry or gene test.
- •Male or female. Patient age ≥ 18 years and ≤ 75 years.
- •Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) score of 0 or
- •Physical state or organ function can tolerate the planned treatment of the study protocol, including systematic chemotherapy, immunotherapy with anti-PD-1 monoclonal antibody (mAb), primary lesion radiotherapy, metastatic lesion radiotherapy, and surgical resection of primary and/or metastatic lesions.
- •No previous surgery or antitumor therapies, including chemotherapy, radiotherapy, or immunotherapy, were administered.
- •Adequate hematological function: absolute neutrophil count (ANC) ≥ 1.5×109/L; platelet count ≥ 100×109/L; hemoglobin level ≥ 90 g/L.
Exclusion Criteria
- •Patients who have previously received surgery, chemotherapy, radiotherapy or immunotherapy for gastric cancer.
- •Patients have a history of cancer in the five years before enrollment except for squamous or basal cell carcinoma of the skin that was effectively treated and superficial bladder cancer, cervical carcinoma in situ and breast cancer in situ that was treated by operation.
- •Pregnant or lactating females or females planning to become pregnant or lactating. Women of childbearing age with a positive pregnancy test or without a pregnancy test in the baseline period. Menopausal women must have stopped menstruating for at least 12 months before being considered to have no chance of pregnancy.
- •Patients who had sexual activity (with the possibility of childbirth) and were unwilling to use contraception during the study period.
- •Patients with a history of allergies to any drugs that may be used in this study, including chemotherapy drugs.
- •History of allogeneic stem cell transplantation or organ transplantation.
- •Vaccinated with live vaccine within 28 days before recruitment.
- •Immunotherapy (interleukin, interferon, thymine) or other experimental treatment was given 28 days before enrollment.
- •History of anti-PD-1, PD-L1, PD-L2 or any other specific T-cell costimulation or checkpoint pathway targeted therapy.
- •History of using steroids (dose \> 10 mg/d prednisone) or other systemic immunosuppressive therapy within 14 days before recruitment, except for patients treated with the following regimen: steroids used for hormone replacement (dose \> 10 mg/d prednisone); local application of steroids with little systemic absorption; short-term (≤ 7 days) use of steroids to prevent allergy or vomiting.
Arms & Interventions
Radiotherapy, Chemotherapy and anti-PD-1 Immunotherapy followed by Surgical Resection
Participants will receive short course hypofractionated radiotherapy (HFRT) for the primary lesion, HFRT or stereotactic body radiotherapy (SBRT) for metastatic lesions, combined with systemic chemotherapy and anti-PD-1 immunotherapy. For patients with HER2-positive cancer (defined as IHC 3+ or 2+/ISH+), trastuzumab is used along with chemotherapy and anti-PD-1 antibody. Then, surgical resections of primary and metastatic lesions are performed as much as possible. For patients who need a widely invasive surgical approach or are inoperable, local ablative therapies such as radiofrequency ablation (RFA) and microwave ablation (MVA) can be alternatives. For patients undergoing surgical resections, postoperative treatment includes chemotherapy, which is determined by the researcher, and PD-1 antibody, which will be maintained until one year after surgery.
Intervention: Radiotherapy targeted to the primary lesion
Radiotherapy, Chemotherapy and anti-PD-1 Immunotherapy followed by Surgical Resection
Participants will receive short course hypofractionated radiotherapy (HFRT) for the primary lesion, HFRT or stereotactic body radiotherapy (SBRT) for metastatic lesions, combined with systemic chemotherapy and anti-PD-1 immunotherapy. For patients with HER2-positive cancer (defined as IHC 3+ or 2+/ISH+), trastuzumab is used along with chemotherapy and anti-PD-1 antibody. Then, surgical resections of primary and metastatic lesions are performed as much as possible. For patients who need a widely invasive surgical approach or are inoperable, local ablative therapies such as radiofrequency ablation (RFA) and microwave ablation (MVA) can be alternatives. For patients undergoing surgical resections, postoperative treatment includes chemotherapy, which is determined by the researcher, and PD-1 antibody, which will be maintained until one year after surgery.
Intervention: Radiotherapy targeted to the metastatic lesions
Radiotherapy, Chemotherapy and anti-PD-1 Immunotherapy followed by Surgical Resection
Participants will receive short course hypofractionated radiotherapy (HFRT) for the primary lesion, HFRT or stereotactic body radiotherapy (SBRT) for metastatic lesions, combined with systemic chemotherapy and anti-PD-1 immunotherapy. For patients with HER2-positive cancer (defined as IHC 3+ or 2+/ISH+), trastuzumab is used along with chemotherapy and anti-PD-1 antibody. Then, surgical resections of primary and metastatic lesions are performed as much as possible. For patients who need a widely invasive surgical approach or are inoperable, local ablative therapies such as radiofrequency ablation (RFA) and microwave ablation (MVA) can be alternatives. For patients undergoing surgical resections, postoperative treatment includes chemotherapy, which is determined by the researcher, and PD-1 antibody, which will be maintained until one year after surgery.
Intervention: Anti-PD-1 monoclonal antibody
Radiotherapy, Chemotherapy and anti-PD-1 Immunotherapy followed by Surgical Resection
Participants will receive short course hypofractionated radiotherapy (HFRT) for the primary lesion, HFRT or stereotactic body radiotherapy (SBRT) for metastatic lesions, combined with systemic chemotherapy and anti-PD-1 immunotherapy. For patients with HER2-positive cancer (defined as IHC 3+ or 2+/ISH+), trastuzumab is used along with chemotherapy and anti-PD-1 antibody. Then, surgical resections of primary and metastatic lesions are performed as much as possible. For patients who need a widely invasive surgical approach or are inoperable, local ablative therapies such as radiofrequency ablation (RFA) and microwave ablation (MVA) can be alternatives. For patients undergoing surgical resections, postoperative treatment includes chemotherapy, which is determined by the researcher, and PD-1 antibody, which will be maintained until one year after surgery.
Intervention: Trastuzumab
Radiotherapy, Chemotherapy and anti-PD-1 Immunotherapy followed by Surgical Resection
Participants will receive short course hypofractionated radiotherapy (HFRT) for the primary lesion, HFRT or stereotactic body radiotherapy (SBRT) for metastatic lesions, combined with systemic chemotherapy and anti-PD-1 immunotherapy. For patients with HER2-positive cancer (defined as IHC 3+ or 2+/ISH+), trastuzumab is used along with chemotherapy and anti-PD-1 antibody. Then, surgical resections of primary and metastatic lesions are performed as much as possible. For patients who need a widely invasive surgical approach or are inoperable, local ablative therapies such as radiofrequency ablation (RFA) and microwave ablation (MVA) can be alternatives. For patients undergoing surgical resections, postoperative treatment includes chemotherapy, which is determined by the researcher, and PD-1 antibody, which will be maintained until one year after surgery.
Intervention: Chemotherapy
Radiotherapy, Chemotherapy and anti-PD-1 Immunotherapy followed by Surgical Resection
Participants will receive short course hypofractionated radiotherapy (HFRT) for the primary lesion, HFRT or stereotactic body radiotherapy (SBRT) for metastatic lesions, combined with systemic chemotherapy and anti-PD-1 immunotherapy. For patients with HER2-positive cancer (defined as IHC 3+ or 2+/ISH+), trastuzumab is used along with chemotherapy and anti-PD-1 antibody. Then, surgical resections of primary and metastatic lesions are performed as much as possible. For patients who need a widely invasive surgical approach or are inoperable, local ablative therapies such as radiofrequency ablation (RFA) and microwave ablation (MVA) can be alternatives. For patients undergoing surgical resections, postoperative treatment includes chemotherapy, which is determined by the researcher, and PD-1 antibody, which will be maintained until one year after surgery.
Intervention: R0 total/subtotal gastrectomy with D2 lymphadenectomy
Radiotherapy, Chemotherapy and anti-PD-1 Immunotherapy followed by Surgical Resection
Participants will receive short course hypofractionated radiotherapy (HFRT) for the primary lesion, HFRT or stereotactic body radiotherapy (SBRT) for metastatic lesions, combined with systemic chemotherapy and anti-PD-1 immunotherapy. For patients with HER2-positive cancer (defined as IHC 3+ or 2+/ISH+), trastuzumab is used along with chemotherapy and anti-PD-1 antibody. Then, surgical resections of primary and metastatic lesions are performed as much as possible. For patients who need a widely invasive surgical approach or are inoperable, local ablative therapies such as radiofrequency ablation (RFA) and microwave ablation (MVA) can be alternatives. For patients undergoing surgical resections, postoperative treatment includes chemotherapy, which is determined by the researcher, and PD-1 antibody, which will be maintained until one year after surgery.
Intervention: Metastasectomy
Radiotherapy, Chemotherapy and anti-PD-1 Immunotherapy followed by Surgical Resection
Participants will receive short course hypofractionated radiotherapy (HFRT) for the primary lesion, HFRT or stereotactic body radiotherapy (SBRT) for metastatic lesions, combined with systemic chemotherapy and anti-PD-1 immunotherapy. For patients with HER2-positive cancer (defined as IHC 3+ or 2+/ISH+), trastuzumab is used along with chemotherapy and anti-PD-1 antibody. Then, surgical resections of primary and metastatic lesions are performed as much as possible. For patients who need a widely invasive surgical approach or are inoperable, local ablative therapies such as radiofrequency ablation (RFA) and microwave ablation (MVA) can be alternatives. For patients undergoing surgical resections, postoperative treatment includes chemotherapy, which is determined by the researcher, and PD-1 antibody, which will be maintained until one year after surgery.
Intervention: Local ablative therapies
Outcomes
Primary Outcomes
Overall survival (OS)
Time Frame: From the time of enrollment, assessed up to 5 years follow-up.
The time from enrollment to death due to any reason.
Secondary Outcomes
- No evidence of disease (NED) rate(Assessed 1 year after treatment)
- Objective response rate (ORR)(From the time of enrollment, assessed up to 5 years follow-up.)
- Progression-free survival (PFS)(From the time of enrollment, assessed up to 5 years follow-up.)
- Toxicities(From the time of enrollment, assessed up to 28 days after the last dose of study therapy)
- Surgical morbidity(During or one month after surgery)
- Surgical mortality(During or one month after surgery)