Clinical trial NCT05505461: Neoadjuvant Immunotherapy and Chemoradiotherapy for Locally Advanced Esophagogastric Junction Adenocarcinoma
Official title: Efficacy and Safety of PD-1 Combined With Long-term Concurrent Neoadjuvant Chemoradiotherapy and Chemotherapy in the Treatment of Resectable Locally Advanced Esophagogastric Junction Adenocarcinoma： A Phase II Study
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: Adenocarcinoma of Esophagogastric Junction
Keywords: PD-1, neoadjuvant therapy, radiotherapy
Lead sponsor: Peking University People's Hospital
Sponsor class: OTHER
First posted: 2022-08-17
Enrollment: 26
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study was to evaluate the effect and safety of concurrent PD-1 antibody-based long-term radiotherapy followed by 2 cycles SOX with PD-1 in patients with locally advanced adenocarcinoma of esophagogastric junction.

Detailed description: The incidence of adenocarcinoma of the esophagogastric junction (AEG) is increasing in Asian countries and Western Contries. Surgical resection is the most important treatment for AEG. However, the recurrence rate is high when surgery is performed alone. The results of CLASSIC, MAGIC, FLOT4, JCOG0501, PRODIGY, RESOLVE, CROSS trial showed that perioperative chemotherapy and pre- or postoperative chemoradiotherapy significantly increase the overall survival rate and disease free survival rate compared to surgery alone. Radiotherapy and immunotherapy can increase sensitivity to each other, and several clinical studies have also showed that PD-1 antibody may significantly prolongs the life.Thus the investigators plan to conduct this clinical trial to evaluate the effect and safety of concurrent PD-1 antibody-based long-term radiotherapy followed by 2 cycles SOX with PD-1 in patients with locally advanced adenocarcinoma of esophagogastric junction.

Subjects will receive long-term radiotherapy (5w) concurrent with PD-1 antibody for 2 cycles, then receive two cycles of SOX regimen combined PD-1 after a week's rest. Surgery will be performed 2 weeks after the last cycle of neoadjuvant treatment. Adjuvant treatment will be started 3 to 8 weeks after surgery, and SOX regimen will be given for 4 cycles.

Eligibility criteria: Inclusion Criteria:

1. Histologically confirmed adenocarcinoma of esophagogastric junction, and Her-2 negative.
2. Clinically diagnosed stage T3+orN+M0, according to CT/MRI scan.
3. No prior anti-tumor treatment, including surgery, chemotherapy, radiotherapy, and targeted therapy.
4. Eastern Cooperative Oncology Group(ECOG) performance status(PS) 0-1.
5. At least one evaluable lesion in abdominal CT/MRI according to RESIST 1.1 is required.
6. Expected survival ≥6 months.
7. Adequate organ function, Hemoglobin ≥90g/L; White blood cells ≥3.0×109/L; neutrophil count ≥1.5×109/L; Platelets ≥100×109/L; Serum creatinine (SCr) ≤ 1.5 times the upper limit of normal (ULN) or creatinine clearance rate ≥ 50ml/min (Cockcroft-Gault formula); Total bilirubin (TBIL) ≤ 1.5 times the ULN; Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) level ≤ 2.5 times the ULN; Urine protein \< 2+; if urine protein ≥ 2+, 24-hour urine protein quantification shows that protein must be ≤ 1 g.
8. Normal coagulation function, no active bleeding and thrombotic diseases: International Standardized Ratio INR≤1.5×ULN; Partial thromboplastin time APTT≤1.5×ULN; Prothrombin time PT≤1.5ULN;
9. Previous use of anti-tumor Chinese medicines, proprietary Chinese medicines, and immunomodulators (such as thymosin, interleukin, etc.) must be ≥ 2 weeks from the start of the study medication;
10. Female patients should not be pregnant or breast feeding. Male should contraception.
11. Able and willing to give informed consent to participate.
12. Those who are expected to have good compliance.

Exclusion Criteria:

1. Existence of other active malignant tumors within 5 years or at the same time.
2. Already received chemotherapy, radiation therapy, targeted or immunotherapy.
3. Have any active autoimmune disease or history of autoimmune disease.
4. Patients with congenital or acquired immunodeficiency.
5. Use of immunosuppressive drugs within 14 days before the study start.
6. Administer live attenuated vaccines within 4 weeks before the study start.
7. Suffering from uncontrolled cardiac clinical symptoms or diseases, such as (1) NYHA II and above heart failure (2) unstable angina pectoris (3) myocardial infarction within 1 year (4) poorly controlled arrhythmia.
8. Patients with past and current interstitial pneumonia, pneumoconiosis, radiation pneumonia, drug-related pneumonia, etc., and severely impaired lung function.
9. Suffering from active pulmonary tuberculosis.
10. Complicated severe infection within 4 weeks before the the study start, or unexplained fever \>38.5°C during the screening period/before the study start.
11. Known history of allogeneic organ transplantation or allogeneic hematopoietic stem cell transplantation.

13. Allergic to any drug in this study. 14. Combined with other severe, acute and chronic diseases that may increase the risk of participating.

15.Participators who had been recruited by other clinical trial within three months.

Primary outcomes:
measure: Pathological Complete Responce (pCR) Rate
timeFrame: Up to 6 months
Secondary outcomes:
measure: R0 Resection Rate
timeFrame: Up to 6 months
measure: Progression Free Survival (PFS)
timeFrame: Up to 3 years
measure: Adverse Events
timeFrame: Up to 6 months
measure: Surgery Morbidity
timeFrame: 30 days and 12-months after surgery
Other outcomes:
Locations:
city: Beijing
country: China
facility: Peking University People's Hospital
state: Beijing
Study officials:
affiliation: Peking University People's Hospital
name: Yingjiang Ye, MD，PhD
role: PRINCIPAL_INVESTIGATOR
References: