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

Not yet recruiting

• Conditions: Gastric Cancer
• Interventions: Combination Product: fruquintinib combined with immune checkpoint inhibitors and chemotherapy

• Registration Number: NCT06464601
• Lead Sponsor: Wuhan University

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Status Verified: 2024-06
• Study First Submitted: 2024-06-10
• Study First Submitted QC: 2024-06-10
• Last Update Submitted: 2024-06-10
• Study First Posted: 2024-06-18
• Last Update Posted: 2024-06-18
• Study Start: 2025-04-01
• Primary Completion: 2026-03-31
• Study Completion: 2027-03-31

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 70

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 & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Cohort 1:neoadjuvant treatment	fruquintinib combined with immune checkpoint inhibitors and chemotherapy	-
Cohort 2:conversion treatment	fruquintinib combined with immune checkpoint inhibitors and chemotherapy	-

Primary Outcome Measures

Name	Time	Method
Corhot2: R0 surgical conversion rate	Time from the first treatment up to 24 weeks	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.
Corhot1: Pathological Complete Response Rate (pCR)	Time from the first treatment up to 12 weeks	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.

Secondary Outcome Measures

Name	Time	Method
Corhot1: Event-Free Survival (EFS)	Time from the first treatment up to 2 years.	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).
Corhot1: 1-year Event-Free Survival (EFS) rate	Time from the first treatment up to 12 months.	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.
Corhot1 and Corhot2: Disease Control Rate (DCR)	corhot1 ：Time from the first treatment up to 12 weeks. Corhot2：Time from the first treatment up to 2 years.	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 and Corhot2: Overall Survival (OS)	Time from the first treatment up to 2 years.	Overall Survival (OS): Time from the first study treatment until death from any cause.
Corhot1: R0 resection rate	Time from the first treatment up to 12 weeks	R0 resection rate: Defined as the proportion of subjects achieving negative margins among those who underwent surgical treatment.
Corhot1 and Corhot2: Objective Response Rate (ORR)	corhot1 ：Time from the first treatment up to 12 weeks. Corhot2：Time from the first treatment up to 2 years.	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 and Corhot2: 1-year Overall Survival (OS) rate	Time from the first treatment up to 12 months.	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.
Corhot2: Curative Surgery Conversion Rate	Time from the first treatment up to 24 weeks	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.
Corhot2: Progression-Free Survival (PFS)	Time from the first treatment up to 2 years.	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).
Corhot1and Corhot2: Adverse events	through study completion, an average of 1 year.	Adverse events during neoadjuvant or conversion therapy, impact on surgery (delay, surgical complications) for corhot1, impact on surgical procedure and postoperative outcomes for corhot2.

Trial Locations

Locations (1)

Zhongnan Hospital of Wuhan University; 🇨🇳 Wuhan, Hubei, China