Neo-Sequence 1: Neoadjuvant Chemotherapy With or Without Antiangiogenesis and Sequential Immunotherapy for HER2-negative MMR-proficient Locally Advanced Gastric or Gastroesophageal Adenocarcinoma

Gastric Cancer Clinical Trial

Official title:

Neo-Sequence 1: Phase 2 Study of Neoadjuvant Chemotherapy With or Without Antiangiogenesis and Sequential Immunotherapy for HER2-negative MMR-proficient Locally Advanced Gastric or Gastroesophageal Adenocarcinoma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05540145
• Other study ID #: 21/489-3160
• Status: Completed
• Start date: May 1, 2022
• Est. completion date: December 31, 2023

Study information

• Verified date: April 2024
• Source: Cancer Institute and Hospital, Chinese Academy of Medical Sciences
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

This is a single-institution, prospective phase II trial designed to evaluate the efficacy of neoadjuvant chemotherapy and sequential immunotherapy in patients with locally advanced esophagogastric junction and gastric adenocarcinoma. Patients with Her-2 positive or dMMR tumors will be excluded from the study. Six cycles of nab-paclitaxel, oxaliplatin and S-1 with or without bevacizumab, followed by three circles of nab-paclitaxel, bevacizumab, with or without S-1 combined with two cycles of PD-1 monoclonal antibody, will be administered as neoadjuvant therapy. Patients will receive different adjuvant treatments depending on the degrees of surgical radicality and the pathological reactions of tumors.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 70
• Est. completion date: December 31, 2023
• Est. primary completion date: December 31, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

1. Be willing and able to provide written (signed) informed consent;

2. Age = 18 years and =75 years.

3. Has a pathologic diagnosis of gastroesophageal or gastric adenocarcinoma, mucinous adenocarcinoma or signet ring cell carcinoma.

4. Imaging (CT/ultrasonography of cervical lymph nodes and supraclavicular lymph nodes/ endoscopy and endoscopic ultrasound) confirmed at the stage of cT3/4a NanyM0(AJCC 8th).

5. Confirmed by immunohistochemistry (IHC) staining or genetic and transcriptional

profiling detection to meet all of the following conditions:

1. Her-2-negative was defined as IHC -, IHC 1+ or IHC 2+ and FISH negative;

2. Mismatch repair-proficient (pMMR).

6. The Eastern Cooperative Oncology Group Performance status (ECOG PS) 0-1;

7. The main organ function meets the following criteria within 7 days before treatment:

1. Hemoglobin (Hb) level =9.0 g/dl.

2. Neutrophil count (ANC)=1.5×10^9/L.

3. Platelet (PLT) =100×10^9/L

4. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) level =2.5×ULN.

5. Serum creatinine (Cr) level =1.0×ULN and creatinine clearance =60 ml/min.

6. Total bilirubin(TBIL) level =1.5×ULN.

Exclusion Criteria:

1. Confirmed at stage IV (AJCC 8th) or unresectable by investigator before enrolling.

2. Patienta have had prior chemotherapy, targeted small molecule therapy, or radiation therapy for the current diagnosis of EGJ cancer or gastric cancer.

3. Patients are allergic to study medication and its ingredients.

4. Patients have experienced or currently have other malignancies within 5 years.

5. Patients have an active infection requiring systemic therapy.

6. Women who are pregnant, breast-feeding or planning to become pregnant during treatment or within 6 months after treatment ends.

7. Patients have a history of psychotropic substance abuse and are unable to quit or have a mental disorder.

8. Patients with other severe acute or chronic conditions that may increase the risk of participation in the study and study treatment, or may interfere with interpretation of study results, and judged by the investigator as not suitable for participation in this clinical trial.

9. Diagnosis of immunodeficiency or active autoimmune disease, receiving or being treated with immunomodulators, systemic steroids or immunosuppressive drugs in the past two years.

10. Patients with gastrointestinal obstruction or uncontrolled bleeding undergo emergency surgery.

11. The proportion of other components in the pathology (such as squamous cell carcinoma, neuroendocrine carcinoma, etc.) exceeds 10%

Related Conditions & MeSH terms

• Adenocarcinoma
• Gastric Cancer

Intervention

Drug:
• SOX plus Paclitaxel with or without antiangiogenesis followed by PD-1 antibody
Drug: Paclitaxel(albumin-bound) 130mg/m2, ivgtt, D1, Q2w Drug: Oxaliplatin 70 mg/m2, ivgtt, D1, q2w Drug: S-1 40mg (body surface area < 1.25m2), bid, D1-8, Q2w 50mg (body surface area >1.25m2, <1.5 m2), bid, D1-8, Q2w 60mg (body surface area >1.5m2), bid, D1-8, Q2w Drug: Bevacizumab, 5mg/kg, ivgtt, D1, Q14d Drug: PD-1 antibody, 200mg, ivgtt, D1, Q21d Patients with Her-2 negative, MMR-proficient locally advanced esophagogastric junction or gastric adenocarcinoma will receive 6 cycles of neoadjuvant chemotherapy with or without antiangiogenesis. After comprehensive evaluations, patients who respond to chemotherapy will further receive 2 cycles of PD-1 antibody comibed with antiangiogenesis and chemotherapy as neoadjuvant therapy. Drug: Pembrolizumab or sintilimab, 100~200mg, ivgtt, D1, Q3w. Patients will make the final decision of PD -1 antibody according to their economic condition.

Locations

Country	Name	City	State
China	National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital	Beijing	Beijing

Sponsors (1)

Lead Sponsor	Collaborator
Cancer Institute and Hospital, Chinese Academy of Medical Sciences

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Event-free survival (EFS)	The time from recruitment to any progression of disease precluding surgery, progression or recurrence of disease after surgery, progression of disease in the absence of surgery, or death from any cause.	From the recruitment to the date of first documented progression or date of death from any cause, whichever came first, assessed up to 3 years
Secondary	Major pathological response	It is defined as residual tumors less than 10% after neoadjuvant systemic therapy according to Mandard grade.	From the date of recruitment to 3 months after all treatment ends
Secondary	Overall survival(OS)	The time from recruitment to the date of death for any reason or the date of last follow-up	From the date of recruitment to the date of death from any cause or the date of last follow-up, assessed up to 36 months
Secondary	R0 resection rate	Rate of microscopically margin-negative resection	From the date of recruitment to 3 months after all treatment ends
Secondary	Adverse events	Adverse events (AEs) of neoadjuvant and adjuvant systemic therapy will be graded and documented according to NCI-CTCAE v5.0 and immune-related Adverse Event, irAE from the beginning of treatment to 3 months since the last dosage of treatment. Documentary will include severity, lasting period and occurrence time. Surgery complications will also be documented.	From the date of recruitment to 3 months after all treatment ends