Clinical trial NCT06464601: A Real-World Study of Neoadjuvant/Conversion Therapy for Locally Advanced or Metastatic Gastric Cancer
Official title: 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
Study type: OBSERVATIONAL
Overall status: NOT_YET_RECRUITING
Conditions: Gastric Cancer
Keywords: fruquintinib
anti-angiogenic targeted therapies
neoadjuvant treatment
conversion treatment
gastric cancer
Lead sponsor: Wuhan University
Sponsor class: OTHER
First posted: 2024-06-18
Enrollment: 70
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Observational model: COHORT
Time perspective: RETROSPECTIVE
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).

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.


Eligibility criteria: 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).

Primary outcomes:
measure: Corhot1: Pathological Complete Response Rate (pCR)
timeFrame: Time from the first treatment up to 12 weeks
measure: Corhot2: R0 surgical conversion rate
timeFrame: Time from the first treatment up to 24 weeks
Secondary outcomes:
measure: Corhot1: R0 resection rate
timeFrame: Time from the first treatment up to 12 weeks
measure: Corhot1: Event-Free Survival (EFS)
timeFrame: Time from the first treatment up to 2 years.
measure: Corhot1: 1-year Event-Free Survival (EFS) rate
timeFrame: Time from the first treatment up to 12 months.
measure: Corhot1 and Corhot2: Overall Survival (OS)
timeFrame: Time from the first treatment up to 2 years.
measure: Corhot1 and Corhot2: 1-year Overall Survival (OS) rate
timeFrame: Time from the first treatment up to 12 months.
measure: Corhot1 and Corhot2: Objective Response Rate (ORR)
timeFrame: corhot1 ：Time from the first treatment up to 12 weeks. Corhot2：Time from the first treatment up to 2 years.
measure: Corhot1 and Corhot2: Disease Control Rate (DCR)
timeFrame: corhot1 ：Time from the first treatment up to 12 weeks. Corhot2：Time from the first treatment up to 2 years.
measure: Corhot2: Curative Surgery Conversion Rate
timeFrame: Time from the first treatment up to 24 weeks
measure: Corhot2: Progression-Free Survival (PFS)
timeFrame: Time from the first treatment up to 2 years.
measure: Corhot1and Corhot2: Adverse events
timeFrame: through study completion, an average of 1 year.
Other outcomes:
Locations:
city: Wuhan
country: China
facility: Zhongnan Hospital of Wuhan University
state: Hubei
Study officials:
affiliation: Zhongnan Hospital
name: Bin Xiong, doctor
role: PRINCIPAL_INVESTIGATOR
References: