A Real-World Study of Neoadjuvant/Conversion Therapy for Locally Advanced or Metastatic Gastric Cancer

A Real-World Study of Neoadjuvant/Conversion Therapy for Locally Advanced or Metastatic Gastric Cancer With Chemotherapy Combined With Immune Checkpoint Inhibitors and Anti-Angiogenic Targeted Agents

Chemotherapy, immune checkpoint inhibitors, and anti-angiogenic targeted therapies have been explored in combination for neoadjuvant and conversion therapies. However, the efficacy of the novel anti-angiogenic agent fruquintinib in combination with immune checkpoint inhibitors and chemotherapy in the neoadjuvant and conversion treatment of locally advanced or metastatic gastric cancer has not been reported. This study aims to observe the efficacy and safety of fruquintinib combined with immune checkpoint inhibitors and chemotherapy in real-world settings.

Study Overview

• Status: Not yet recruiting
• Conditions: Gastric Cancer
• Intervention / Treatment: Combination product: fruquintinib combined with immune checkpoint inhibitors and chemotherapy

• Study Type: Observational
• Enrollment (Estimated): 70

Contacts and Locations

• Study Contact: Name: ChunWei Peng, Doctor; Phone Number: 13476196566; Email: whupengcw@whu.edu.cn
• Study Contact Backup: Name: Bin Xiong, Doctor; Phone Number: 13886029351; Email: binxiong1961@whu.edu.cn

Study Locations

• China
  • Hubei
    • Wuhan, Hubei, China, 430000
      • Zhongnan Hospital of Wuhan University
      • Contact: ChunWei Peng, doctor; Phone Number: 134 7619 6566; Email: whupengcw@whu.edu.cn
      • Contact: Bin Xiong, doctor; Phone Number: 138 8602 9351; Email: binxiong1961@whu.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: N/A

• Sampling Method: Non-Probability Sample

Study Population

Histologically confirmed gastric or gastroesophageal junction adenocarcinoma. For neoadjuvant therapy cohort: candidates for Initial potentially curative surgery with cII, cIII, or cIVA stage disease (>cT2N0-3M0 or cT0-4N+M0); no distant metastasis. For conversion therapy cohort: patients with locally advanced unresectable or stage IV metastatic disease (per AJCC 8th edition).

Description

Inclusion Criteria:

Patients must meet all of the following criteria to be enrolled in this study:

1. Age ≥18 years and ≤75 years;
2. Either gender;
3. Histologically confirmed gastric or gastroesophageal junction adenocarcinoma. For neoadjuvant therapy cohort: candidates for Initial potentially curative surgery with cII, cIII, or cIVA stage disease (>cT2N0-3M0 or cT0-4N+M0); no distant metastasis. For conversion therapy cohort: patients with locally advanced unresectable or stage IV metastatic disease (per AJCC 8th edition). Pre-treatment imaging (CT or MRI, PET-CT, etc.) must indicate only one of the following unresectable factors:

(1) Lymph node metastasis around the abdominal aorta (2) Virchow lymph node metastasis (left supraclavicular lymph node metastasis) (3) Resectable liver metastases: 2 to 5 metastatic lesions, total diameter >5 cm and ≤8 cm, tumor invades the vena cava or portal vein (4) Lung metastases (5) Isolated peritoneal implantation

4. Have received chemotherapy, immune checkpoint inhibitors, and fruquintinib for at least 2 cycles. For the neoadjuvant therapy cohort, patients who have not previously received anticancer treatment (radiotherapy, chemotherapy, targeted therapy, or immunotherapy, etc.). The patients are eligible for inclusion in the analysis set if they have received fruquintinib treatment for at least 2 cycles and have undergone at least one baseline tumor assessment. All patients included in the efficacy analysis are included in the safety analysis set.

5. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 before treatment.

6. Expected survival time of >6 months before neoadjuvant therapy and >3 months before conversion therapy.

7. No significant organ dysfunction or drug contraindications before receiving neoadjuvant or conversion therapy.

8. There is no mandatory requirement for target lesions. Objective response rate (ORR) assessment is based on all evaluable patients, regardless of the presence of target lesions. For patients without target lesions, those assessed as non PR/non PD will be analyzed as stable disease (SD).

Exclusion Criteria:

Patients meeting any of the following criteria are not eligible to enter the study:

1. History of other primary malignant tumors, except: (1) complete remission of malignant tumors at least 2 years before enrollment and no need for other treatment during the study period; (2) adequately treated non-melanoma skin cancer or malignant melanoma without evidence of disease recurrence; (3) adequately treated in situ carcinoma.
2. Conversion therapy cohort: Diagnosis of HER2-positive gastric or gastroesophageal junction adenocarcinoma.
3. Conversion therapy cohort: Evidence of distant metastases beyond oligometastases as defined in the inclusion criteria before the first dose of study treatment (such as brain, bone, etc.).
4. Female patients who are pregnant or lactating.
5. Known allergy (Grade 3 or higher allergic reaction) or contraindication to anti-angiogenic drugs, any monoclonal antibody, or chemotherapy drug components.
6. Use of non-study drug treatments during the study period that may interfere with the analysis.
7. Patients who did not undergo any tumor efficacy assessment after receiving neoadjuvant or conversion therapy.
8. Less than 2 cycles of fruquintinib neoadjuvant or conversion therapy.
9. Patients with insufficient follow-up information as judged by the investigator (such as not returning to the hospital for treatment or efficacy assessment after initial treatment).

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Cohort 1:neoadjuvant treatment	Combination product: fruquintinib combined with immune checkpoint inhibitors and chemotherapy; Chemotherapy Drugs: Selection based on clinical guidelines/indications and patient condition.For example, recommended chemotherapy regimens: XELOX or SOX. Immune Checkpoint Inhibitors: Selection based on clinical guidelines/indications and patient condition, including but not limited to PD-1 inhibitors, PD-L1 inhibitors. Fruquintinib: 3mg (starting dose), PO (once daily). Dosing schedule and dosage can be adjusted based on concurrent chemotherapy and immune checkpoint inhibitors. Have received fruquintinib treatment for at least 2 cycles.
Cohort 2:conversion treatment	Combination product: fruquintinib combined with immune checkpoint inhibitors and chemotherapy; Chemotherapy Drugs: Selection based on clinical guidelines/indications and patient condition.For example, recommended chemotherapy regimens: XELOX or SOX. Immune Checkpoint Inhibitors: Selection based on clinical guidelines/indications and patient condition, including but not limited to PD-1 inhibitors, PD-L1 inhibitors. Fruquintinib: 3mg (starting dose), PO (once daily). Dosing schedule and dosage can be adjusted based on concurrent chemotherapy and immune checkpoint inhibitors. Have received fruquintinib treatment for at least 2 cycles.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Corhot1: Pathological Complete Response Rate (pCR)	Pathological Complete Response Rate (pCR), defined as no residual tumor cells in the surgical specimen of the primary tumor and lymph nodes (ypT0N0); corresponds to TRG grade 0.	Time from the first treatment up to 12 weeks
Corhot2: R0 surgical conversion rate	R0 surgical conversion rate：The proportion of subjects who achieve complete R0 resection of both the primary gastric lesion and any metastases among all subjects receiving the conversion therapy regimen.	Time from the first treatment up to 24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Corhot1: R0 resection rate	R0 resection rate: Defined as the proportion of subjects achieving negative margins among those who underwent surgical treatment.	Time from the first treatment up to 12 weeks
Corhot1: Event-Free Survival (EFS)	Event-Free Survival (EFS): Time from initiation of neoadjuvant study treatment until first documented progression, recurrence/metastasis, or death from any cause (whichever occurs first, without progression/recurrence at the time of death).	Time from the first treatment up to 2 years.
Corhot1: 1-year Event-Free Survival (EFS) rate	1-year Event-Free Survival rate: Survival rate of patients who, from initiation of neoadjuvant study treatment, have not experienced progression, recurrence/metastasis, or death from any cause at 12 months.	Time from the first treatment up to 12 months.
Corhot1 and Corhot2: Overall Survival (OS)	Overall Survival (OS): Time from the first study treatment until death from any cause.	Time from the first treatment up to 2 years.
Corhot1 and Corhot2: 1-year Overall Survival (OS) rate	1-year OS rate: Survival rate of patients who have not experienced progression or death from any cause at 12 months from the first study treatment.	Time from the first treatment up to 12 months.
Corhot1 and Corhot2: Objective Response Rate (ORR)	Objective Response Rate (ORR): Proportion of patients with target lesions who achieve a complete response (CR) or partial response (PR) among all treated patients.	corhot1 ：Time from the first treatment up to 12 weeks. Corhot2：Time from the first treatment up to 2 years.
Corhot1 and Corhot2: Disease Control Rate (DCR)	Disease Control Rate (DCR): Proportion of patients with target lesions who achieve a complete response (CR), partial response (PR), or stable disease (SD) among all treated patients.	corhot1 ：Time from the first treatment up to 12 weeks. Corhot2：Time from the first treatment up to 2 years.
Corhot2: Curative Surgery Conversion Rate	Curative Surgery Conversion Rate: The proportion of subjects who undergo potentially curative surgical resection of both the primary gastric lesion and any metastases among all subjects receiving the conversion therapy regimen.	Time from the first treatment up to 24 weeks
Corhot2: Progression-Free Survival (PFS)	Progression-Free Survival (PFS): Defined as the time from initiation of the study treatment regimen until the first radiographic disease progression, postoperative disease recurrence, or death (whichever occurs first). This can be calculated separately for surgical and non-surgical patients, with surgical patients considering postoperative disease recurrence or death (whichever occurs first).	Time from the first treatment up to 2 years.
Corhot1and Corhot2: Adverse events	Adverse events during neoadjuvant or conversion therapy, impact on surgery (delay, surgical complications) for corhot1, impact on surgical procedure and postoperative outcomes for corhot2.	through study completion, an average of 1 year.

Collaborators and Investigators

• Sponsor: Wuhan University
• Investigators: Principal Investigator: Bin Xiong, Doctor, Zhongnan Hospital of Wuhan University

Study record dates

Study Major Dates

• Study Start (Estimated): April 1, 2025
• Primary Completion (Estimated): March 31, 2026
• Study Completion (Estimated): March 31, 2027

Study Registration Dates

• First Submitted: June 10, 2024
• First Submitted That Met QC Criteria: June 10, 2024
• First Posted (Actual): June 18, 2024

Study Record Updates

• Last Update Posted (Actual): June 18, 2024
• Last Update Submitted That Met QC Criteria: June 10, 2024
• Last Verified: June 1, 2024

More Information

Terms related to this study

• Keywords: neoadjuvant treatment; gastric cancer; fruquintinib; anti-angiogenic targeted therapies; conversion treatment
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Stomach Diseases; Stomach Neoplasms; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors
• Other Study ID Numbers: HMPL-013-C2-GC02

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No