Skip to main content
OpenTrials
Completed

NCT Number: NCT05540145

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

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.

Completed

Looking for future studies?

Notify Me

Key information

Conditions

Gastric Cancer Digestive System Diseases Digestive System Neoplasms Gastrointestinal Diseases Gastrointestinal Neoplasms Neoplasms Neoplasms by Site Stomach Diseases Stomach Neoplasms

Age range

18 year–75 year

Sex eligibility

All sexes

Study type

Observational

Primary location

National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital

Beijing, Beijing Municipality, 100021, China

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Be willing and able to provide written (signed) informed consent;
  • Age ≥ 18 years and ≤75 years.
  • Has a pathologic diagnosis of gastroesophageal or gastric adenocarcinoma, mucinous adenocarcinoma or signet ring cell carcinoma.
  • 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).
  • Confirmed by immunohistochemistry (IHC) staining or genetic and transcriptional profiling detection to meet all of the following conditions:
  • Her-2-negative was defined as IHC -, IHC 1+ or IHC 2+ and FISH negative;
  • Mismatch repair-proficient (pMMR).
  • The Eastern Cooperative Oncology Group Performance status (ECOG PS) 0-1;
  • The main organ function meets the following criteria within 7 days before treatment:
  • Hemoglobin (Hb) level ≥9.0 g/dl.
  • Neutrophil count (ANC)≥1.5×10^9/L.
  • Platelet (PLT) ≥100×10^9/L
  • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) level ≤2.5×ULN.
  • Serum creatinine (Cr) level ≤1.0×ULN and creatinine clearance ≥60 ml/min.
  • Total bilirubin(TBIL) level ≤1.5×ULN.

Exclusion criteria

  • Confirmed at stage IV (AJCC 8th) or unresectable by investigator before enrolling.
  • Patienta have had prior chemotherapy, targeted small molecule therapy, or radiation therapy for the current diagnosis of EGJ cancer or gastric cancer.
  • Patients are allergic to study medication and its ingredients.
  • Patients have experienced or currently have other malignancies within 5 years.
  • Patients have an active infection requiring systemic therapy.
  • Women who are pregnant, breast-feeding or planning to become pregnant during treatment or within 6 months after treatment ends.
  • Patients have a history of psychotropic substance abuse and are unable to quit or have a mental disorder.
  • 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.
  • Diagnosis of immunodeficiency or active autoimmune disease, receiving or being treated with immunomodulators, systemic steroids or immunosuppressive drugs in the past two years.
  • Patients with gastrointestinal obstruction or uncontrolled bleeding undergo emergency surgery.
  • The proportion of other components in the pathology (such as squamous cell carcinoma, neuroendocrine carcinoma, etc.) exceeds 10%

Treatment and study plan

SOX plus Paclitaxel with or without antiangiogenesis followed by PD-1 antibody

Drug

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.

Primary outcomes

  1. Event-free survival (EFS)

    Time frame: 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

    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.

Secondary outcomes

  1. Major pathological response

    Time frame: From the date of recruitment to 3 months after all treatment ends

    It is defined as residual tumors less than 10% after neoadjuvant systemic therapy according to Mandard grade.

  2. Overall survival(OS)

    Time frame: 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

    The time from recruitment to the date of death for any reason or the date of last follow-up

  3. R0 resection rate

    Time frame: From the date of recruitment to 3 months after all treatment ends

    Rate of microscopically margin-negative resection

  4. Adverse events

    Time frame: From the date of recruitment to 3 months after all treatment ends

    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.

Sponsors and collaborators

Lead sponsor

Cancer Institute and Hospital, Chinese Academy of Medical Sciences

Other

Registry information

Official study 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

Important dates

Study start
2022
Primary completion
2023
Study completion
2023
First posted
Sep 14, 2022
Registry last updated
Apr 16, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Related clinical trials

Published trials that share one or more normalized conditions with this study.